TW201143772A - High penetration prodrug compositions of antimicrobials and antimicrobial-related compounds - Google Patents

Abstract

The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of antimicrobials and antimicrobial-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

Description

201143772 VI. Description of the invention: [Technical field to which the invention pertains] This application is a continuation of the application for the application of the patent application for the application of the patent application for the application of the patent application of the company. + The child's water is given priority. The US application was incorporated by reference in March. The present invention relates to a drug sputum which is permeable to one layer or which can be used as a biological barrier of a Α 层 layer, and the pharmaceutical composition in the prevention, Ling ° 4- ^ ^ 士° 〆 矛 / 或 或 或 或 或 σ σ σ σ Human and animal antibacterial and antibacterial-related compounds can be used to treat symptoms or diseases. The present invention also relates to methods of using these pharmaceutical compositions for the selection of new pharmacies: options and methods for diagnosing the symptoms of organisms. [Prior Art] An antibacterial agent is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, and protists, and can destroy viruses. The main types of antibacterial agents include, for example, antibiotics for treating bacterial-related symptoms, antiviral drugs for treating virus-related symptoms, antifungal drugs for treating fungal-related symptoms, and antigenic biopharmaceuticals for treating symptoms associated with protozoa. Beta-lactam antibiotics are a class of antibiotics that contain a four-membered indoleamine core in their molecular structure. More than 100,000 β-endoamine antibiotics are prepared by semi-chemical synthesis or chemical synthesis (L.A. Mitscher, et al., Antibiotic and Antimicrobial).

Drugs, in D.F. Smith, Ed., Handbook of Stereoisomers: Therapeutic Drugs, Boca Raton, FL, CRC Press, 1989; R.B.

Morin and M. Gorman Eds., Chemistry and Biology } 4 201143772

Beta-lactam Antibiotics, Volumes 1-3, New York, Academic Press, 1982; and A.L. Demain and N.A. Solomon, Eds.,

Antibiotics Containing the Beta-lactam structure, Vols 1 and 2, Handbook of experimental Phgarmacology, vol. 67, New York, Springer, 1983). Examples of β-endoamine antibiotics include penicillin derivatives, cephalosporins Cephalosporins 'monocyclic β-indolamines (mon〇bact; ams), carbapenems, β_indolease inhibitors 卬 七 (10) 脱 ln ln hlhlbltors) Sulfonamide and quinolones ° With the wide application of antibacterial agents, drug resistance has become a common and serious problem due to the variation of pathogens over time. Therefore, the development of new antimicrobial agents is an urgent and challenging task. Numerous antibacterial agents can be administered intravenously, intramuscularly, subcutaneously,

Administration by rectal route. A disadvantage of oral antibiotics is that the gastrointestinal tract is insufficiently absorbed by the expectorant. The vein is only painful, and the veins are mainly injected with subcutaneous or intramuscular injections without other risks, such as needle injuries, infections or other damages.

Another ancient, earthy a D advantage of using music. This method is avoided in the liver and "intestines:: medicine. Local administration has several effects on the first-pass effect of the drug (7)-s providing an appropriate local drug delivery concentration, which can indicate the systemic exposure associated with oral drug therapy to a predetermined site of action. Pain in the position of Fish, inflammation or infection: blood == for effective treatment of the tip', and a considerable amount is reached - t i 5 201143772 The exact concentration required to deliver the pain or injury site is U. For most antibacterial agents, topical administration does not achieve effective treatment and can be effectively and efficiently' thus preventing, slowing down, therefore, new compositions are needed in the art to deliver to symptomatic (eg, disease) sites of action or to treat symptoms While reducing side effects. [Summary of the Invention]

Aspects of the present invention provide a high penetrative prodrug (HPP) or a high permeability composition (High Penetration Compositi〇n, Hpc) containing a linker (HnkeO covalently attached to a transport unit) Functional units. Unless otherwise indicated, the terms "HPP" and "HPC" may be used alone or in combination, and interchanged with each other in the present invention. In certain embodiments, the functional unit of HPP or HPC contains a parent drug. A portion (m〇iety) in which it is desirable to efficiently and efficiently deliver and/or deliver the parent drug to an organism such that transport of the parent drug across one or more biological barriers is desired. In a mode, the functional unit may be hydrophilic, lipophilic, or amphoteric (ie, both hydrophilic and lipophilic). For example, the lipophilicity of a functional monosaccharide may be intrinsic or by functioning The hydrophilicity of the unit. ί5 is obtained by conversion to a lipophilic moiety. In certain embodiments, the carboxyl unit of the functional unit (carboxyl gr0Up), amino group (arnin〇gr0Up), guanidine g (guanidine g) Roup) or other hydrophilic hydrazines may be protected with an alkyl, an aryl 201143772 (aryl) ' or a heteroaric ester or an anionic amino acid (aniide gr0Up) to render the HPP or HPC more lipophilic. In an embodiment, the functional unit of HPP or HPC contains an antibacterial agent or a part of an antibacterial agent-related compound. The antibacterial agent is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, protists, and the like, and destroys the virus. It is an agent containing an antibacterial agent structure, an antibacterial agent metabolite structure, or an antibacterial agent or an antibacterial agent metabolite after the HPP or HPC penetrates one or more layers of the biological barrier. The antibacterial agent-related compound further includes an antibacterial agent. Or an analog or mimetic of an antimicrobial metabolite, or an agent that mimics an antibacterial agent or an analog or analog of an antibacterial agent metabolite after the HPP or HPC has penetrated one or more layers of the biological barrier. Examples of the antibacterial agent include For example, antibiotics for the treatment of bacterial-related symptoms, antiviral drugs for the treatment of virus-related symptoms, antifungal for the treatment of fungal-related symptoms And antibiotic biopharmaceuticals for treating symptoms associated with protists. Examples of antibacterial agents include, but are not limited to, P_neutamine antibiotics, serotonin and quinolone class I antibiotics. Examples include, but are not limited to, penicillin derivatives 'cephalosporins, penicillin antibiotics, monocyclic ρ·indanamines, carbapenems, beta-endoprostanase inhibitors, and combinations thereof. Penicillin derivatives Examples include, but are not limited to, amino penicillins (eg, amoxicillin, ampicillin, and epicurilin), carboxypenicillin (eg, carbenicillin^ ί. ^ 3 7 201143772 ticarcillin and tem〇cillin, ureidopenicillins such as azl〇cillin, piperacillin and mezlocillin, beauty Western (mecillinam), stone yellow > sulbenicillin, benzathine penicillin, penicillin G (benzylpenicillin), penicillin v (phenoxymethylpenicillin (ph Enoxymethylpenicillin)), penicillin 〇

(allylmercaptomethylpenicillinic) > procaine penicillin, oxacillin, methicillin, nafcillin, cloxacillin (cl〇xaciiiin), diclocillin (dicloxacillin) ), flucloxacillin (fiuci〇xaciliin), pivampicillin, hetacillin 'becampicillin, metampicillin, talampicillin, compound amoxicillin (co_am〇xiclav) (amoxicillin + clavulanic acid) and lincillin (piperaciiii〇n). Examples of cephalosporin antibiotics include, but are not limited to, cephalexin, cephalothin, cefazolin, cefaclor, cephalosporin. Cefuroxime, cefmandole, cefotetan, cefoxitin, ceforanide, ceftrixone, cefotaxime, cephalosporin Cefpodoxime proxetil, ceftazidime, cefepime, cefoperazone, ceftizoxime, cefixime, and cefpirome. Examples of penem antibiotics include but not s 8 201143772 Limited to: Faropenem. Examples of monoamine cyclic antibiotics include, but are not limited to, aztreonam and tigemonam. Examples of carbapenem antibiotics include, but are not limited to, biapenem, doripenem, ertapenem, imipenem, meropenem, and par Niperan (panipenem). Examples of beta-inactamase inhibitors include, but are not limited to, tazobactam ([2S-(2a,3p,5a)]-3-indolyl-7-oxo-3-(111-1) ,2,3-azido-1-ylmethyl)_4-thia-1-azabicyclo[3.2.0]glyced -2-decanoic acid-4,4 sodium dioxide salt)([2S -(2alpha,3beta,5alpha)]-3-Methyl-7-oxo-3-(lH-l,2,3 -triazol-l-ylmethyl)-4-thia-l-azabicyclo[3.2.0]heptane- 2-ca rboxylic acid 4,4-dioxide sodium salt), sulbactam ((2S,5R)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo) [3.2.0] Heptane-2-carboxylic acid-4, 4 sodium dioxide) ((2^,5^)-3,3-dimethy l-7-oxo-4-thia-l-azabicyclo[3.2. OJhept ane-2-carboxylic acid 4,4-dioxide sodium) and clavulanic acid # ((2R,5R,Z)-3-(2-hydroxyethylidene)-7-oxo_4-oxa-1 -azabicyclo[3.2.0]heptane-2-carbonyl acid)((2,5A,Z)-3-(2-hydroxyethylidene)-7-ox〇-4-oxa-l-aza-bicyclo[ 3.2.0]heptane-2-carboxylic acid)) ° Examples of other antibiotics include, but are not limited to: [(N-benzyloxycarbonylamino)indolyl]-phosphate mono-(4-nitrophenyl) ester sodium salt ( [(N-benzyloxycarbonyla Mino)methyl]-phosphonic acid mono-(4-nitrophenyl) ester sodium salt), [(N-benzyloxyaminoguanidine) 201143772 methyl]-phosphate mono-(3- °pyridyl) ester sodium salt ( [(N-benzyloxycarbonylamino)methyl]-phosphonic acid

Mono-(3-pyridinyl) ester sodium salt), sulfanilamide (4-aminobenzenesulfonamide), sulphate (5-oxo-3-sulfonamide) (2-[4-(7V-pyrimidin-2-ylsulfamoyl)phenyl]-linked amino)cyclooctane-1,4-diene tracula) (sulfasalazine (6-oxo-3-(2-) [4-(A^-pyridin-2-ylsulfamoyl)phenyl]hydrazono) cyclohexa-l,4-dienecarboxylic acid)), 1-cyclopropyl-6-aero-4-oxo-indole-pyridazine-1- 1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-yl-quinoline-3 carboxylic acid and nalidixic acid (l-ethyl- 7-Methyl-4-oxo-[1,8]naphthyridine-3-carboxylic acid)((l-ethyl-7-methyl-4-oxo-[l ,8]naphthyridine-3-carboxyl ic acid) ). Examples of sulfa antibiotics include, but are not limited to, sulfadisodimidine, sulfanilamide, sulfadiazine, sulfisoxazole, Sulfamethoxazole, sulfadimethoxine, sulfamethoxypyridazine, sulfacetamide, sulfadoxine, acetamidine . Acetazolamide, bumetanide, chlorthalidone, clopamine, furosemide, hydrochlorothiazide, hydrochlorothiazide. Indapamide, mefruside, metolazone, xipamide, diclofenac [")] 10 201143772 (dichlorphenamide), Dozzo Dorzolamide, acetazolamide, ethoxzolamide, sultiame, zonisamide, mafenide, celecoxib Examples of (celecoxib), darunavir, probenecid, sulfasalazine, and sumatriptan quinolone antibiotics include, but are not limited to, Cinoxacin, flumeequine, nalidixic acid, oxolinic acid, σ ratio piromidic acid, 0 citrate Acid), rosoxacin, ciprofloxacin, enoxacin, fleroxacin, lomefloxacin, nadifloxacin Norfloxacin, ofloxacin, pefi〇xacin, Rufioxacin (rufi〇xacin) 'balofloxacin, gatifloxacin xacin, grePafl〇xacin, levofloxacin, moxisha Moxifloxacin, pazufl〇xacin, sparfloxacin, temafi〇xacin, tosufloxacin, ciinafi〇xacin , gemifloxacin, sitafl〇xacin, trovafloxacin, prulifloxacin, garenoxacin, hexosporin (ecinofi〇xacin) , delafloxacin (delafl0xacin) and nalidixic acid. Examples of antiviral agents include, but are not limited to, rifampicin, r ζ 201143772 zanamivir and osemi Wei (oseitamivir). Examples of antifungal agents include, but are not limited to, polyene antifungal agents (e.g., natamycin 'rimicodin', filipin, nystatin, both sexes Bactinomycin B (amphotericin B;) and candicin (imidazc) le antifungals) (eg: miconazole, ketoconazloe, clotrimazole) (clotrimazole), econaz〇ie, benbenbenz, bifonazole, butoconazole, fenticon 0, fenticonazole, isoconazole, oxicon Oxiconazole, sertaconaz〇ie, sulconazole and tioconazole, triazoles antifungals (eg fluconazole) Fluconaz〇ie), itraconazole, isavuconaz〇ie, levacon, ravuconazole, p〇saconaz〇ie, volcanic squat ( Voriconazole) and terconazole, thiaz〇le antifungals (eg: A Abafungin, allyamines (eg, terbinafine, amorolfine, naftifine, and butenafine), Echinocandins (eg, anidulafungin, caspofungin, and micafungin) and other antifungal agents such as benzoic acid, cyclopyridamole ( Ciclopirox), tolnaftate, undecylenic acid, flucytosine, griseofulvin, and haloprogin. 12 201143772 Examples of antibiotic biopharmaceuticals include, but are not limited to, elornithine, furazone (furaz〇Ud〇ne), mela sterol (melarsoPro1), metronidazole, ornidazole ), par〇m〇mycin sulfate, pentamidine ^ pyrimethamine and tinidazole ° In some embodiments, the transport unit of HPP or Hpc Contains a protonatable amino group that promotes or enhances the transport or leaching of Hpp or Hpc across one or more layers of the biological barrier. In certain embodiments, the protonatable amino group can be infiltrated by the HPP or HPC biological barrier? Under the condition of 1^, it is basically beadized. In some embodiments, the amino group can be reversibly protonated or deprotonated. In certain embodiments, the linker is covalently linked to a functional unit of the HPP and a transport unit comprising a bond that can be cleaved after the HPP has penetrated one or more layers of the biological barrier. The cleavable bond includes, for example, a covalent bond, an ether bond, a thioether bond, a guanamine bond, an ester bond, a thioester bond, a carbonate bond, an amino phthalate bond, a phosphate bond or a hydrazone bond. In some embodiments, HPP or HPC of an antibacterial or antibacterial-related compound contains one or two primary and secondary salts that can exist in protonated form at physiological pH (physi〇i〇gical pH). Or tertiary amino group. In certain embodiments, HPP or HPC contains a primary, secondary, or tertiary amino group that can exist in protonated form at physiological pH. Another aspect of the invention relates to a pharmaceutical composition comprising at least one antibacterial or antibacterial agent-related compound of HPP or HPC and a pharmaceutically acceptable carrier [1] 13 201143772. Another aspect of the invention relates to a method of permeating a biological barrier using HPP or HPC of an antimicrobial or antimicrobial related compound. Another aspect of the invention relates to the use of HPP or HPC of an antibacterial or antibacterial agent-related compound to diagnose the occurrence, development, or mitigation of symptoms in an organism. In certain embodiments, the Hpp (or Hpc) or its function το疋 is measurable. In certain embodiments, the Hpp or its functional unit is itself measurable or labeled or conjugated to a measurable label. Another aspect of the invention relates to a method of screening functional units, connectors, or transport units to achieve desired characteristics. Another aspect of the invention relates to a method of preventing, alleviating, or treating a condition in an organism by administering the composition according to the invention to an organism. In certain embodiments, the method relates to the administration of a therapeutically effective amount of an antimicrobial or antimicrobial-related compound of HPP, or a pharmaceutical composition thereof, to a therapeutically effective combination of an antibacterial or antibacterial agent in an organism. Lu can be used to treat symptoms. In certain embodiments, the symptoms treated by the method include, but are not limited to, pain, injury, and symptoms associated with the microorganism. Symptoms associated with microorganisms refer to symptoms caused by microorganisms such as bacteria, fungi, protists, and viruses. For example, symptoms caused by bacteria (bacteria-related symptoms), symptoms caused by protists (protozoa-related symptoms), symptoms caused by fungi (fungi-related symptoms), and symptoms caused by viruses (virus-related symptom). Bacterial-related symptoms include 'eg' infection (eg infection of an organ such as liver, lung, stomach, brain, kidney, heart, ear, eye, nose, mouth, tongue, colon, pancreas, gallbladder, ten 1 [S1 14 201143772 One finger, rectum stomach, colorectal, intestine, vein, respiratory system, vascular, anorectal and anal pruritus, respiratory tract infection, upper: suction tract infection, urinary tract infection, nosocomial infection, fake Cytobacterial infection, coagulase-positive grape ball _ infection (such as · skin infection, poisoning, acute infection! raw "endometrial dog, septicemia, necrotizing pneumonia", post-implantation infection, with Zhizhishan Opportunistic infections of diseases and pneumonia), quarantines (eg, bubonic plague and lung plague), anthrax (eg, skin charcoal m and gastrointestinal, Lai _,

* 4 bacillary pertussis, acute enteritis, parrot fever, non-gonococcal urethritis, trachoma, neonatal inclusion body conjunctivitis, sexually transmitted lymphogranuloma, pseudomembranous colitis, gas gangrene, food poisoning, anaerobic bacteria Cellulitis, dysentery, two menstrual meningitis, hemorrhagic colitis, hemolytic uremic therapy, rabbit fever, pneumonia, Tiansheng Ιθ TT ju J, month, /bei ^, Legionnaires' disease, gram Heat, leptospirosis, listeriosis, leprosy, tuberculosis, tuberculosis, gonorrhea, neonatal ophthalmia, septic arthritis, flow

Spastic meningitis, Huafu Erqing in human A, · · not & ^ (acute fulminant meningococcal 'positive m spot heat, typhoid type salmonellosis (handsome h. heart rain ype Salm〇 Nell () sis ), accompanied by gastroenteritis and: bacillary dysentery, bacillary disease, cystitis, meninges 2 = membranous inflammation, otitis media, sinusitis, syphilis, necrotizing fasciitis, glomerular pharyngitis, scarlet fever, wind Thirsty 埶 ^ 激 L L........ Impetigo, erysipelas, calving and cholera. Probiotic-related symptoms include ... right body disease. Fungal-related symptoms include, for example, dysentery, sleeping sickness and Toxoplasmosis, heart-boiled disease, coccidioidomycosis, Brazilian germination, sporotrichosis, and bacillus, and f-cytoplasmic disease, interface bacteria. Virus-related symptoms winter g 201143772 Epidemic smuggling of steam fever and AIDS. A variety of ^ = where the 'Caf or HPC's pharmaceutical composition can pass the 夕 种 达 给 给 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物 生物Limited to 'oral route, vaginal it, ^ cavity approach, external route, rectal route, right-handed arrest!, The aerosol route < the path, the skin route, the eye ^ two = skin route, the percutaneous route, in a fresh L route, subcutaneous route, and / or note can pass, /, consistent application, HPP or HPC's drug group·· :=Γ Skin topical, subcutaneous and/or injection route. : 'Pros and only' and do not want to be defined by any specific mechanism, can be treated locally in a symptomatic effective amount of sputum or HPC is administered at a high concentration, and a lower overall dose is achieved compared to sputum administration. Advantages of the invention are also = for example, 'avoid systemic administration, reduce side effects (eg, injection pain, gastrointestinal or renal response' or other Side effects), and possible new treatment modalities due to the local concentration of Η% or live agents. The present invention further includes 'for example, sputum or HPC can be administered systemically to organisms. How to achieve bioavailability more efficiently, infiltrate biological barriers that have been difficult to cross (such as the 'blood-brain barrier and blood-broth barrier), and new treatments through biological barriers. [Embodiment] high penetration prodrug * HPP) or high penetration composition 1 HPC) Structure of High Paint # # One aspect of the invention relates to a high penetration pr〇drug 'HPP or a highly permeable composition (higji 16 201143772 penetration composition, HPC). The term "high permeability prodrug" or "HPP" or "high permeability composition" or "HPC" in the present invention refers to a composition which contains a functional unit covalently linked to a transport unit by a linker. The functional unit of HPP or HPC contains a portion of the parent drug that has the following properties: 1) delivery of the parent drug or HPP/HPC into the organism and/or transport of the parent drug across the biological barrier; 2) the HPP/HPC permeable Or reading the HPP/HPC across the bioscreen I1 early and 3) can be lysed to convert a portion of the parent drug to _# as the metabolite of the parent drug or parent drug. In certain embodiments, the functional unit can be hydrophilic, lipophilic or amphoteric (i.e., both hydrophilic and lipophilic). The lipophilic moiety of the functional unit can be intrinsic' or obtained by converting one or more hydrophilic moieties of the functional unit to a lipophilic moiety. For example, the lipophilic moiety of the functional unit can be converted to a lipophilic group by organic synthesis of one or more hydrophilic groups of the functional unit. Examples of the practical hydrazine of the hydrophilic group include, but are not limited to, thiol, thiol, thiol, amino, phosphate/phosphonate, sulfhydryl and carbonyl. The lipophilic moiety formed by modifying these hydrophilic groups includes, but is not limited to, ethers, thioethers, esters, thioesters, carbonates\aminodecanoates, decylamines, querysates, and phthalates. In certain embodiments, the functional unit can achieve lipophilicity by acetylation or deuteration. In certain embodiments' functional units can achieve lipophilicity by esterification. In certain embodiments, the parent drug of HPP or HPC can be selected from the group consisting of an antimicrobial agent and an antimicrobial-related compound. A portion of the antimicrobial or antimicrobial related compound can be further converted to lipophilic as described above.

I 17 201143772 Sexual part. An antibacterial agent is a substance that kills or inhibits bacteria, (4), or microorganisms such as protists and can destroy viruses. The main types of antibacterial agents include, for example, antibiotics for treating bacterial-related symptoms, antiviral drugs for treating virus-related symptoms, antifungal drugs for treating fungal-related symptoms, and antiparasitic drugs for treating parasitic-related symptoms. The antibacterial agent-related compound is an antibacterial agent structure, an antibacterial agent metabolite structure or an agent structure which can be metabolized into an antibacterial agent or an antibacterial agent metabolite. The antibacterial agent-related compound further includes an analog or mimetic of the antibacterial agent, or an agent which can be metabolized into an antibacterial agent or an analog or mimic of the antibacterial agent metabolite after the HPP/HPC penetrates one or more layers of the biological barrier. Examples of the antibacterial agent include, for example, antibiotics for treating bacterial-related symptoms, antiviral agents for treating virus-related symptoms, antifungal agents for treating fungal-related symptoms, and antigenic biopharmaceuticals for treating symptoms associated with protozoa. Examples of φ antibiotics include, but are not limited to, P-endoxime antibiotics, sulfonamides, and quinolone antibiotics. Endosteroid antibiotics are used in the art and are used in the evening symptoms. In the present invention, β_indoleamine antibiotic refers to a compound containing a β-namidamine core. Examples of β-endoamine antibiotics include, but are not limited to, cephalosporin derivatives, penicillin antibiotics, monocyclic β-endoyamines, carbenoxenes, β-endoamines Enzyme inhibitors, and combinations thereof. Examples of penicillin organisms include, but are not limited to, amino penicillins (eg, amoxicillin, ampicillin, and eticillin), carboxy penicillins (eg, Penicillium punctate... 201143772, texasillin, and temocillin) ), ureido-based penicillins (eg, azlocillin, infracillin, and mezlocillin), mecillin, sulfacillin, benzathine, penicillin G (benzylpenicillin), penicillin v (phenoxymethylpenicillin), penicillin Ally (allylmercapt〇methylpenicillinic), procaine penicillin oxacillin, oxicillin, nafcillin, cloxacillin, acesulfame, fluoxetine, pirazicillin, hetacillin, bacilcillin, metan Xilin, ampicillin, compound amoxicillin (amoxicillin + clavulanic acid) and indazin. Examples of cephalosporin antibiotics include, but are not limited to, cephalexin, cefotaxime, cefazolin, cefaclor, cefuroxime, cefmenudene, cefotetan, cefoxitin, ceftriax, ceftriaxone, Cefotaxime, cefpodoxime, ceftazidime, cefepime, cefotaxime, ceftizoxime, cefixime and cefpirome. Examples of penem antibiotics include, but are not limited to, faropenem. Examples of monoamine cyclic antibiotics include, but are not limited to, aztreonam and tigimomon. Examples of carbapenem antibiotics include, but are not limited to, biapenem, doripenem, ertapenem, imipenem, meropenem, and panipenem. Examples of beta-inactamase inhibitors include, but are not limited to, tazobactam ([2S_(2a,3|3,5a)]_3_methyl-7-oxo (1H匕2,3-® nitrogen- 1-ylindenyl-4-pyrene-1-azabicyclo[3.2.〇]g//竣西夂·4 '4 sodium dioxide salt), sulbactam (2S,5R)-3,3 -diindolyl-7-oxothiazepinebicyclo[3.2.0]heptane-2-carboxylic acid-4,4 sodium dioxide spear^ravic acid ((2R,5R,Z)-3-(2 -hydroxyethylidene)_7-oxo-4-oxazahecyclo[3.2.0]heptane-2·carboxylic acid). Examples of other antibiotics include: · [(N-卞 裁 氨基 氨基 amino) sulfhydryl] _ sulphate mono _ (heart nitro stupid) 酉 纳 临, | (N-卞 几 基 amino) methyl] Filling with acid mono-(3-η ratio), IS i 19 201143772 salt, sulfonamide, (4-aminobenzenesulfonamide), sulfasalamide alpha-pyridyl (6-oxo-3-(2) -[4-(ΛΤ-pyrimidin-2-ylsulfamoyl)phenyl]yreneamino)cyclooctyl- 4,4-diencarboxylic acid), 1-cyclopropyl-6-fluoro-4-oxo Pyridazine _ 丨 _ _ quinoline _3 carboxylic acid and Tsai acid (1_ethyl-7-fluorenyl-4-oxo-[M]naphthyridine_3_carboxylic acid). Examples include, but are not limited to, a reductive amine dimethylisodazole, a sulfonamide, a sulfadiazine, a sulfisoxazole, a sulfamethoxazole, an amine dioxime (tetra), a pyroxamine, a sulfonamide Stuffed, edetamine, sulphate, bumetanide, qi. ketones, acetaminophen, dexamethasone, hydrogen hydrazine, "inducing dapamine, mefsit, metolazon, Hippamine, bis-pentaamine, dorzolamide, etoxazolamide, oxazolamide, succinimide, zonisamide, amimidamide, celecoxib, derivir, propyl yellow Shu, azadixamine bitumen and sumatriptan. Examples of quinolone antibiotics include, but are not limited to, cinoxacin...",. (b) tasha, quinone quinone, nalidixic acid, oxolinic acid, pyrrolic acid, pyridoxic acid, argon, various itzasin Gatifloxacin, sparazine, cilostazin, ciprofloxacin, enoxacin, fluroxacin, lomezosin, fluorodioxide: ofloxacin, pefloxacin, flurazepam Sacine, Barosin, Gepasarsin, Levovoxacin, Moxisarsin, Pazuaxin, Temasacin, Tosapxine, Clinxine, Gemifluoxacin, Pu Luli, Gareth (4), Eisesarin, Delafloxacin and Nalidixic Acid. Examples of anti-viral agents include, but are not limited to, oseltamivir. Examples of ... thousand, zanamivir and antifungal agents include, but are not limited to, polyratic natamycin, mitomycin, filipin, system, 4, s] J-solid, amphotericin 20 201143772 Candesin), cut antifungal agents (such as: micon saliva, ketone Kang salivakang, joint stupid saliva, bucon, fentanyl saliva, isokang saliva: sputum, azole, sitakon Oxazole, thiconazole, and beta sikangwa) a "six cis Kang Kang. Sit, Yi Qukang. Sit, Aishaku: Λ) Fu antifungal agents (such as: U u Tian Fu Kang saliva, Po Sha Kang Sal, #Riconazole, and Teconazole), thiophene antifungal agents (eg: Ababang)

The second category = Qi 1 (such as: TBI Caifen, Amorolfine, Natto; and cloth J does not distinguish), _ white pigments (such as: Anifen, Caspofung and Mika and other anti- Fungicides such as benzoic acid, ciclopirox, decyl naphthyl ester, flucytosine, griseofulvin and hapronol. A. Examples of antibiotic biopharmaceuticals include, but are not limited to, elonin (e1〇rnithine) ), oral sevotonone, mela swell, metronidazole, sulphate = paromomycin sulfate, pentamidine, pyrimethamine and tinidazole. In certain embodiments, antibacterial or antibacterial agents The functional unit of ΗΡΡ of the related compound contains a moiety having the formula:

Stereoisomers and pharmaceutically acceptable salts thereof are included. Unless otherwise stated in the specification 'γ is selected from the group consisting of Η, 〇H, ISiHCHO, NHC(=0)R6, 〇C(=〇)CH3, 〇C(=0)R6, 〇CH3, 〇c2H5 , 〇R6, ch3, c2h5, r6, Ch3S〇3, r6S〇3 N〇2 CN, CF3, C2F5, C3F7, 〇CF3, OC2F5, 〇C3F7, F, Br, I, 201143772

The structural formula NS-3 \ is selected from the group consisting of: structural formula NS-4, and structure

Cl and substituted and unsubstituted alkoxy groups; NS_1, structural formula Ns_2, structural formula ns formula NS-5:

Structure NS-1 structural formula NS-2 structural formula NS-3 structural formula NS-4 structural formula NS-5 where X! is selected from the following groups: Η, OH, OCH3, 〇 (: 2115, or6, c (=o)nh2, ch2oc(=o)nh2, ch2oc(=o)ch3, ch2oc(=o)r6, oc(=o)ch3, 0C(=0)R6, CH2OCH3, CH3, C2H5, R6, C卜F, Br, I, HC=CHCH3, HC=CH2, CH2OCH3, CH2OR6, S(CH2)n-NHR7, structural formula Xi_l, structural formula X]-2, structural formula X!-3, structural formula Xi-4 , Structural formula Xi-5, structural formula Xr6, structural formula X "7, structural formula, structural formula X!-9, structural formula X "10, structural formula Xrll, structural formula Χι-12, structural formula Xrl3" structural formula Xrl4 , Structural Formula X1 -15, Structural Formula X1 -16, Structural Formula X1 -17, Structural Formula X! -18, Structural Formula Xi-19, Structural Formula 1-20, Structural Formula X!-2 Bu Structural Formula, - 22, structural formula X1 - 2 3, structural formula X1_ 2 4, structural formula X1 - 2 5, structural formula X丨-2 6, structural formula X1 - 2 7, structural formula X1_ 2 8, structural formula X1 - 2 9, Structural formula X! - 3 0, Structural formula Xi-3 Bu structure Xr32, Structural formula XdS, Structural formula Χ, -34, Structural structural formula U6, Structural structural formula Χ!-38, Structural formula X1 - 3 9 Structural formula X 1 - 4 0, Structural Formula X1 _ 41, Structural Formula X! - 4 2 'Fly t S i 22 201143772 Structural Formula X!-43, Structural Formula Χγ44, Structural Formula X!-45, Structural Formula Χγ46, Structural Formula Xi -47, structural formula -!-48, structural Χγ49, structural Χ!-50, structural Xi-5 卜 structure Χ!-52, structural Χ!-53, structural Xi-54, structural 乂Factory 55, structural type Xi-56, structural type Xj-57, structural type Xi-58, structural formula X!-59, structural formula X!-60, structural formula X!-6 Bu structure type Xi-62, structural formula Xr63, structural formula X!-64, structural formula Xi-65, structural formula Xr66, structural formula Xi-67, structural formula X!-68, structural formula Χγό, structural formula Xi-70, structural formula Xi-71, structural formula X "72, structural Χ γ73, structural Χ γ74, # structural Χι-75, structural Χ!-76, structural X!-77, structural Xi-78, structural X!-79, structural Χ^ δΟ, structural formula X “81 and structural Xi-82:

R5

Structural formula X^l, structural formula Xi-2, structural formula X "3,

Structure Χ!-4, Structure Χ!-5, 23 201143772

5 R Structural formula Xr6 Structural formula X!-7, Structural formula ΧΓ #

Χ2 Structure Xi-9

Structural formula Xi-10 n==n H2C-N, 〆-R5 h2c——ν' r5 Structural formula Xi-11

nR5 Structure Xi-13 Structure X!-12

n Rs Structural formula Xi-14 24 201143772

Structure X!-15,

Structure X!-16,

Structural Xi-18,

Y3

N 丫3

O Structural formula Xi-19, y2

Y1 structural formula x "21, structural Xi-20,

Structural formula Xi-22, 25 201143772

丫3 Structure Xi-24 Υι

_丫3

Υι Structure Χγ27

0 ORs q 〇R5

|c2J .cHl

tc2J 〇 h2

CH \ /n NHR36 I NH

0 C CH \ /nvNHC(=NR36)NHR46 h2 I

R6〇 CH \〇 NH-AA

NH H2 /C\ RqO CH

NH-AA Structural Formula X "29 Structural Formula Xi-30 26 201143772 〇 h2 or5 I h2

Conh2 HN - AA

NHC(=NR36)N hr6 NH H3C\h/^ I \〇

NH-AA Structure Xi-31, Structural Formula X!-32, OMe

H2 structural formula X!-33, structural Xi-34,

Structural Xi-35,

Structural formula Xi-37, structural formula X!-38, 27 201143772

Nhr37

s s Structural Xr41, Structural Formula X!-42, Structural Xi-43

Structural Χγ44

Structural formula X!-45 # r5 ?Γ ?2

Re

N--II \ V r5 r6

-N, fj-NHR7 -N

O 0, CH〇

Structural Formula X "46, O Structural Formula X: -47 γ3 r5

R5 y2 'Y3

Yi Y2 r6 \ , 丫 4 [s] 28 201143772 Structure X!-48,

Γ2 structural formula Xi-49, mr8 people -

Structure Xi-50, structure x "51,

Father 5

^0NR7

Structural Xi-58, Structural Formula X!-59, 29 201143772 n-o-r8

Structural X!-60, Structural Xi-61, Υι

Structural Xi-62, Structural Formula X "63, Structural Formula X "64,

• Edit (4), Structure Xl-66,

Structural Xi-67,

Structural formula Xi-68, 30 201143772

Structural Χι-69

Structural Xi-70 χ35 χ5

Υΐ

Γ2 Structural formula Χ!-72 Structural formula Χ!-71 γ2 χ5

Ν V Υι

Υ3 γ3 Structure Χ, -74 Structure Χ!-73

ο and ι八为 w

Structural formula, -76, νη2 〇 Structure Χ!-77 Structure Χ "78 s] 31 201143772

Structured Χ!-79,

Structural Xi-80,

Structural Xi-81, structural Xi-82,

Rs and Y together are R6〇CH2C(R5)=, or are themselves selected from the following groups: R600CCH(NHR7)(CH2)nC(=0)NH-, R600CCH(NHR7)(CH2)nSC(=0) NH-, CF3SCH2C(=0)NH-, CF3CH2C(=0)NH-, CHF2SCH2C(=0)NH-, CH2FSCH2C(=0)NH- 'NH2C(=0)CHFS-CH2C(=0)NH- ' R7nhch(c(=o)ow)ch2sch2c(=o)nh-, R7NHCH(L1-L4-L2-W)CH2SCH2C(=0)NH- 'CNCH2SCH2C(=0)NH-,CH3(CH2)nC(= 0) NH-, R7N=CHNR7CH2CH2S-, r7n=c(nhr7)nhc(=o)-, r7n=c(nhr7)nhc(=o)ch2, CH3C(C1)=CHCH2SCH2C(=0)NH-,( CH3)2C(OR6)-, CNCH2C(=0)NH- 'CNCH2CH2S-' R7HN=CH(NR7)CH2CH2S-, ch2=chch2sch2c(=o)nh-, CH3CH(OH)-, CH3CH(OR8)-, , (ch3) 2ch-, rt 32 201143772 CH3CH2-, CH3(CH2)nCH=CH(CH2)mC(=0)NH-, structural formula R s -1, structural formula R s - 2, structural formula R s - 3. Structural formula R s - 4, structural formula Rs-5, structural formula Rs-6, structural formula Rs-7, structural formula Rs-8, structural formula Rs-9, structural formula Rs-10, structural formula Rs-11 , structural formula Rs-12, structural formula Rs-13, structural formula Rs-14, structural formula Rs-15, structural formula Rs-16, structural formula Rs-17, structural formula Rs-18, structural formula Rs-19, structure Formula Rs-20, structural formula Rs- 2 structural formula Rs-22, structural formula Rs-23, structural formula Rs-24, structural formula Rs-25, structural formula Rs-26, structural formula Rs-27, structural formula Rs-28, fragrant structure type Rs-29 , structural formula Rs-30, structural formula Rs-3, structural formula Rs-32, structural formula Rs-33, structural formula Rs-34, structural formula Rs-35, structural formula Rs-36, structural formula Rs-37, structure Formula Rs-38, structural formula Rs-39, structural formula Rs-40, structural formula Rs-4 Bu structural formula Rs-42, structural formula Rs-43, structural formula Rs-44, structural formula Rs-45, and structural formula Rs-46;

Structural formula Rs-1, structural formula Rs-2, 33 201143772

Structural formula Rs-3, structural formula Rs-4,

Structural formula Rs-5, structural formula Rs-6,

Structural formula Rs-8, structural formula Rs-7, 34 201143772 丫1

Structural formula Rs-9,

Structural formula Rs-10 丫2

Structural formula Rs-11,

CONH-

'CONH- r7—

Y1 Λ~

Structural formula Rs-15, 'CONH- structural Rs-13, OCHO structural formula Rs-14, 〇r7 Y3 structural formula Rs-16 r r fly t O j 35 201143772

Structural formula Rs-17, NORo

Υι H2 C, CONH

Structural formula Rs-19, NHR7 H2 structural formula Rs-20,

^-CONH Structural Formula Rs-21, Structural Formula Rs-22,

Structural formula Rs-23, structural formula Rs-24, 36 201143772

Structural formula Rs-25, structural formula Rs-26,

Structural formula Rs-27,

丫2 Structure Rs-29,

Structural formula Rs-30, 37 201143772 ο4 Ο Y1-N N——CONH—C——CONH- , CONH- Structure Rs-31,

"COOW Structure Rs-32 ch3 r7hn

Ch3 n , ch3

h3cT, S CONH- Structural Rs-33 Structural Formula Rs-34 HO, /Me

O h3c γ2- if O '0 structural formula Rs-3 5

, CONH - r7HN

CONH - Structural Rs-3 6

Yi Y3 Structure Rs-37 "CONH——

CONH-

COOH Structural Formula Rs-3 8 38 201143772 H3c

Υι

Structural formula Rs-40, structural formula Rs-39,

Structural formula Rs-43, structural formula Rs-44, 39 201143772

Structural formula Rs-45,

W is selected from the group consisting of H, substituted and not s'46; = cyclinyl, substituted and unsubstituted heterocyclic: substituted and substituted, substituted and unsubstituted diluted, unsubstituted Substituted and unsubstituted aryl, ge #unsubstituted alkynyl, amino, pharmaceutically acceptable σ# substituted heteroaryl, protonated structural formula, structural formula w and unsubstituted primary amino group, structural formula Wa , configuration W-5, structural formula w, structural formula W-3, structural formula w_4, knot type W-9, structural formula w, i〇, & structural formula W-7, structural formula w_s, structural formula W- 13. Structural configuration W 11, structural W-12, structural configuration W_17 and structural structural W-15, structural W_16, knot

Re

Structural Wa, structural formula W ~~

HA

, structural formula W_2 structural formula W-3,

201143772 Structural formula W-5, structural formula W-6, structural formula W-4

Structural formula W-7, structural formula W-8,

Structural formula W-9,

Structural formula W-10, structural formula W-11,

Structural formula W-12, ΗΑ

Structural formula W-13, structural formula W-14,

Structural formula w-15,

The structural group W-18; r NH, NR6, CHCH3, Ο; and the group consisting of integers, the K structural formula W-16, the structural formula W-17, Z are selected from the following groups: CH2, S, SO, SO CHCH2CH3 , CHR6, R6, -c(=o), and AA represent any amino acid; each m and n can be independently selected from 0 41 201143772 such as: 〇, 1, 2, 3, 4, 5, 6, 7, 8 , 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20; HA is selected from the group consisting of: none, and pharmaceutically acceptable acids, such as: hydrochloric acid, hydrogen acid, hydrogen Mothic acid, & xiao acid, sulfuric acid, sulfurous acid, acid, acid, phosphonic acid, isonicotinic acid, acetic acid, lactic acid, salicylic acid, citric acid, tartaric acid, pantothenic acid Pantothenic acid), bitartaric acid, ascorbic acid, succinic acid, maleic acid, gentisinic acid, fumaric acid, fumaric aci Gluconic acid, glucaronic acid, saccharic acid, formic acid, benzoic acid, glutamic acid (glu Tamic acid), methanesulfonic acid, ethanesulfonic acid, benzoic acid, p-toluenesulfonic acid and pamoic acid; κ is selected from the group consisting of π ... n24=U)OR6, substituted and un=, Substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted sessile bases, substituted and unsubstituted alkoxy groups, "based, substituted and unsubstituted s-substituted nicotine groups, taken from multiple gas generations and not Substituted alkynyl, substituted and unsubstituted dilute, taken heteroaryl, wherein any CH2 of R+ may be replaced by a substituted and unsubstituted other pharmaceutically acceptable group; p, or any hydrocarbon

R1~R3 may be independently selected from the group consisting of: substituted, unsubstituted cyclonicotinyl, substituted and unsubstituted soil substituted and unsubstituted hydrocarbon oxygen & unsubstituted heterocyclic hydrocarbon and unsubstituted The aryl group, the substituted and unsubstituted unsubstituted fluorenyl group, the substituted heteroaryl group; and the substituted and unsubstituted 42[S] 201143772 5 and the heart can be independently selected from the τ column group: H, -ce〇)NH2. ch2ch2〇r6 , CH2CH2N(CH3)2 . CH2CH2N(CH2CH3)2, α, F, Br, [substituted and unsubstituted cycloalkyl, substituted (tetra) = nicotine, and unsubstituted hydrocarbyl Base, substituted and unsubstituted ring = substituted aryl, substituted and "nonyl substituted and un(tetra), substituted and unsubstituted nicotinyl) hetero: two;.: substituted oxime; taken two hydrocarbon W; Li-L4 -L2-W and base, 5·float base, 2 3 ) R5, 2_milk small imidazolidinyl, benzene, 3-—虱dH-茚-5-, 4~-glycol, substituted and unsubstituted Hydrocarbyl group, substituted and substituted; 4^^5·cai _3_ and unsubstituted heterocycloalkyl, substituted and unsubstituted, substituted block, substituted and unsubstituted alkoxy, substituted And unfed base, substituted and unsubstituted #未Substituted cyclic hydrocarbons -c(,, fluorene-mono-;; substituted and unsubstituted heteroaryl, quaternary 7 and Rm, each independently selected from the group consisting of -CH3NHC(=〇)CH2C^^R Qin C(NHR6) Nhc (which substituted and unsubstituted substituted and unsubstituted county, substituted and unsubstituted and unsubstituted alkoxy, substituted aryl, substituted and unsubstituted heteroaryl: alkynyl, substituted and unsubstituted, Substituted and unsubstituted t- and unsubstituted hydrocarbons ^-L4-L2-W^C(=0).W; Γ »-· 1 43 201143772 Κ·8 and R38 can be independently selected from the following groups : η, F, Cl, Br, I, CH3, C2H5, CF3, CH2CH2F, CH2CH2CU, CH2CH2Br 'CH2CH2I, CH2CHF2, CH2CF3, CH2f, CH2C1, CH2Br, CH2I, C^NR#7, CH(NHR7)CH2C(= 〇) NH2, CSH7, c4H9, C5HU, R6' C(=〇)R6 . c(=〇)NH2 > CH2C(=0)NH2 > CH20C(=0)NH2 > P〇(OR5)〇r6 C(CH3)2C(=〇)〇R6 . CH(CH3)C(=〇)〇R6, ch2c(=0)0r6, c(=0)_w, Li L4_L2_w and w, substituted and unsubstituted Fluorohydrocarbyl, substituted and unsubstituted hydrocarbyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted hydrocarbon, substituted and unsubstituted Substituted hydrocarbon amino groups, substituted and unsubstituted polyfluorohydrocarbon groups, underived #unsubstituted hydrazine groups, and substituted and unsubstituted hydrocarbon groups; each independently selected from the group consisting of: none, H, CH2C ( =0) 0R", the base of the substituted, unsubstituted and unsubstituted cyclic hydrocarbon unsubstituted alkoxy group, substituted and = county, substituted and unsubstituted block, taken:: substituted and unsubstituted heteroaryl ; base, and take 2 from the following groups: Yi, u, -a, and 2, nhr6, CH ' c RD 2 5, C3F7, 〇CF3, 〇C2f5, =:, r group, and unsubstituted: = two: substituted heterotetrakis, substituted and unsubstituted and unsubstituted nicotine, substituted and unsubstituted nicotinyl, substituted: unsubstituted and unsubstituted hydrocarbylamino tj 44 201143772 and substituted and Unsubstituted alkoxy group; X3 is selected from the group consisting of: none, Η, N3, S03w, F, Cl, Br, 〇Η, 〇CH3, 〇R6, CH3, r6, c(=o), c(= s), c(=〇)〇w, OW, L1-L4-L2-W and I; X4 is selected from the group consisting of: none, N, CH and CY!; X5 and X35 are each independently selected from the following groups: none , C(=0), C(=S), 〇C(=〇), CH2, CH, s, 0, and NR5;

Yi, Y31, Y2, Y32, Y3 and γ4 are each independently selected from the following groups: _ Η, OH, ow, OC (=〇) W, LiH-W, 0C (=0) CH3, CH3, C2H5, C3H7, C4H9, R6, S03R6, CH2OR6, CH20C(=0)R6, CH2C(=0)0R8, 0CH3, 〇C2H5, or6, ch3so2, R6S02, CH3S03, R6S03, N02, CN, CF3, 〇CF3, CH2(CH2) nNR5R6, CH2(CH2)n0R6 'CH(C(=0)NH2)NHR6, CH2C(=〇)NH2, F,

Br, I, a, ch=chc(=o)nhch2c(=o)ow, CH=CHC(=0)NHCH2L1-L4-L2-W 'NR8C(=〇)R5 > 参so2nr5r8,c(=o R5, sr5, substituted and unsubstituted polyfluorohydrocarbyl, substituted and unsubstituted hydrocarbyloxy, substituted and unsubstituted hydrocarbylthio, S and unsubstituted hydrocarbylamino, substituted and unsubstituted polyfluorohydrocarbyl, Substituted and unsubstituted halohydrocarbyl groups and substituted and unsubstituted hydrocarbon groups; L! is selected from the group consisting of: none, 〇, s, U L3- -S-L3·, _N(L ) _, -N ( L3)-CH2-0, -N(L3)-CH2-N(L5)-, ·〇_(^Η2-0-, -0-CH(L3)-0, and -S-CH(L3)- 〇_ ;

L2 is selected from the group consisting of: none, O, S, ς TU [3- -SL", · Να )-, -N(L3)-CH2-0 ' -N(L3)-CH2-N(L5) - ' -〇-ch2-o Γ Γ· Ί t ^ i 45 201143772 -〇-CH(L3)-〇, -S-CH(L3)-〇. -N(L3)-L5- and Lq;

-OL -NL· B L4 is selected from the following groups: c = o, os 1STII C· -0L, _L5- NII • c - 丨/〇l3 o "L5-- and 〇u Group Pair: Mother: II LC2, 〇L4, h and I5 may each independently be selected from the following cores. ( ) aL6' substituted and unsubstituted nicotinic group, unsubstituted π-cycloalkyl-substituted and unsubstituted heterocyclic hydrocarbon group, substituted # unsubstituted Aryl, substituted and unsubstituted ge and nicotinyl, substituted and unsubstituted hydrocarbylthio, substituted and unsubstituted polygasohydrocarbyl and substituted and unsubstituted her-based, mesocentric or hydrogenated materials Fractionation—Steps are substituted with G, s, p /, or any other pharmaceutically acceptable group; 3. L6 can be independently selected from the group consisting of: τ, substituted and unsubstituted cycloalkyl, substituted and unsubstituted = Hetero- and unsubstituted aryl, substituted and unsubstituted heterotetra(4), = and unsubstituted hydrocarbyloxy, substituted and unsubstituted hydrocarbylthio, unsubstituted hydrocarbylamino, substituted and unsubstituted A multi-gas group and a substituted-and-substituted hydrocarbyl group in which any carbon atom or hydrogen atom can be substituted. :s'NKC^Wc'dcw, cubic, heteroaryl or cyclic group; [S] 46 201143772 L7 may be independently selected from the group consisting of η, 〇H, α and unsubstituted hydrocarbyl, substituted And unsubstituted rings, broad, I, substituted heterocyclic ketone groups, substituted and unsubstituted aryl groups, di- and unsubstituted aryl groups, substituted and unsubstituted alkoxy groups, substituted and unsubstituted Substituted and unsubstituted hydrocarbon amino groups, substituted and unsubstituted polygasohydrocarbyl groups and substituted unsubstituted hydrocarbyl groups in which any carbon or hydrogen atom can be respectively substituted, S, N, P(0)0L6 , CH=CH, CHL6, CL6L7,

Substituted with a hetero group, a heteroaryl group or a cyclic group; and any CH2 group may be substituted with a aryl group, a thio group or an amine group NH. In certain embodiments, the functional unit of the HPP or HPC of the antibacterial or antibacterial agent-related compound comprises a moiety having a structure selected from the group consisting of structural formula FIM, structural formula FP-2, structural formula FP-3, structural formula FP-4, structural FP-5, structural FP-6, structural FP-7, structural FP-8, structural FP-9, structural FP-10, structural fp-11, structural FP- 12. Structural formula FP-13, structural FP-14, structural FP-15, structural FP-16, structural FP-17, structural FP-18, structural FP-19, structural FP-20, Structural formula FP-21, structural FP-22, structural FP-23, structural FP-24, structural FP-25, structural FP-26, structural FP-27, structural FP-28, structural FP-29, structural FP-30, structural FP-3, structural FP-32, structural FP-33, structural FP-34, structural Fp-35, structural FP-36, structural FP- 37. Structural FP-3 8, structural FP-39, structural FP-40, structural FP-41, structural FP-42, structural FP-43, structural FP-44, structural FP-45 , structural type FP-46, structural type fp-47, structural type FP-48, structural type FP-49, structural type FP-50, structure Fp-5 Bu structure type FP-52, structure type FP-53 h 201143772 Structure type FP-54, structural type FP-55, structural type FP-56, structural type FP-57, structural type FP-58, structural type FP -59, structural FP-60, structural FP-61, structural FP-62, structural FP-63, structural FP-64, structural FP-65, structural FP-66, structural FP-67 Structural FP-68, structural FP-69, structural FP-70, structural FP-71, structural FP-72, structural FP-73, structural FP-74, structural FP-75, structure Formula FP-76, structural FP-77, structural FP-78, structural FP-79, structural FP-80, structural FP-81, structural FP-82, structural FP-83, structural FP -84, structural FP-85, _ structural FP-86, structural FI-1, structural Π-2, structural FI-3, structural FI-4, structural FI-5, structural FI- 6. Structural formula FI-7, structural type FI-8, structural type FI-9, structural type FI-10, structural type FI-11, structural type FI-12, structural type FI-13, structural type FI-14, Structural formula FI-15, structural FI-16, structural FI-17, structural FI-18, structural FI-19, structural FI-20, structural FI-21, structural FI-22, structure FI-23, structural type FI-24, structural type FI-25, structural type Π-26, structural type FI-27, structural type FI-28, structural type FI-29, structural type FI-30, structural type FI- 31. Structural type Lu-FI-32, structural type FI-33, structural type FS-1, structural type FS-2, structural type FS-3, structural type FS-4, structural type FS-5, structural type FS-6 , Structural formula FS-7, Structural formula FS-8, Structural formula FS-9, Structural formula FS-10, Structural formula FS-11, Structural formula FS-12, Structural formula FS-13, Structural formula FS-14, Structure Formula FS-15, Structural Formula FS-16, Structural Formula FS-17, Structural Formula FS-18, Structural Formula FS-19, Structural Formula FS-20, Structural Formula FT-1, Structural Formula FT-2, Structural Formula FT -3, structural FT-4, structural FT-5, structural FT-ό, structural FT-7, structural FT-8, structural FT-9, structural FT-10, structural FT-11结 _s] 48 201143772 Structural Formula FT-14, Structural Formula FT-15, and Formula FT-12, Structural Formula FT-13 Structural Formula FT-16:

Structural FP-1

Structural FP-2

Structural FP-3

Structural FP-4 0

Structural FP-5 Structural FP-6

49 201143772 Structural FP-7 Structural FP-8

LrUd

Structural FP-10 Structural FP-9

Structural FP-13 Structural Formula FP-14

Structural FP-15 Structural FP-16 50 201143772

L31-L34-L32-R6 LrL4-L2-R5 L31-L34-L32-R6 Structural Formula FP-17 Structural FP-18

Γ3 structural formula FP-19

Structural FP-21

HA H2N,

Structural FP-23 Structural FP-20 Re

Structural formula FP-24 51 201143772

Structural FP-25

Structural FP-27 Structural Formula FP-26

Structural FP-29 Structural FP-28

Structural FP-30

Structural FP-31 Structural FP-32

52 201143772 Structural FP-34 Structural FP-3 3

Structural FP-35 Structural FP-36

Structural FP-37 Structural FP-38

Structural FP-40

Structural FP-41

Structural formula FP-42 53 201143772

Structural FP-43 Structural FP-44

0 eight. Structural FP-46

54 201143772

Structural FP-51

Structural FP-53 Structural FP-54

Structural FP-55

Structural FP-56

Structural FP-57

55 201143772 Structural FP-59

Structural FP-60

Structural FP-62

Structural FP-63 Structural FP-64

Structural FP-66 Structural FP-65

Structural formula FP-68 201143772

Structural FP-69 Structural FP-70

Structural FP-71

Structural FP-73 Structural FP-72

Structural FP-75

Structural FP-76

Structural FP-77

IR5 Structure FP-78 57 201143772

Structural FP-79

Structural FP-80

Structural FP-81

Structural FP-82 c! - N --5

Structural type FP-83 h2c

Structural FP-84

58 201143772 Structural FI-1 Structural FI-2 Structural FI-3

Structural type FI-4 structural type FI-5

Structural type FI-7

Structural formula FI-9 ·)

Structural type FI-10

Structural type FI-12 structural type FI-11

59 201143772

, fii

Structural type FI-15

Structural formula FI-17 _ Structure FI-16

Structural FI-19 Structure FI-18

Structural type FI-22

Structural type FI-21

Structural type FI-23 60 201143772

Structural type FI-24

Structural type FI-2-5

r

N. /> Structure FI-26

0 Structure type FI-28

Structural type FI-29

II Ο N,

f* structural type FI-30

Y4 structural type FI-32 structural type FI-31

Λλ U I II

Xs [s] 61 201143772 Structural FS-l

Structural FS-2

m

Structural formula FS-6

Och3 och3 OCH3

OCH3 OCH3 Structure FS-‘

Structural FS-9 Structural FS-8

Structural FS-10

62 201143772 Structural FS-ll Structural FS-12 Structural FS-13 雠

Structural FS-15 Structural Formula FS-14

Structural FS-16

Structural FS-18

Xs

丫3

R5-X5

丫4 .ch2

Structural FS-20 Structural Formula FS-19 _ Y2 Y3

Och3

Structural FT-1 Structural FT-2 Structural FT-3

丫2, /N

N^V3 h3c

H2c ch2

N CH2 I I R7 X7 ch3

63 201143772 Structural FT-4

Structural FT-5 Structural Formula FT_6

Structural FT-7 Structural FT-8

Structural FT-11 Structural FT-12 Structural FT-13 64 201143772

The structural formula FT-14 includes its stereoisomers and FT-16 pharmaceutically acceptable salts of the formula FT-15, wherein: Υ32 ' Υ3 and Υ4 of n5 R5 ' R7 ' X<: ' y \T ν

5 八35, Υι, Υ2, υ31 Definitions are the same as before; 31 has the same meaning as above, La has the same definition as L2 above, L34 has the same definition as L4 above, and in some embodiments, _Li_L4· ^- and L3i-L34_L32_ are independently selected from the following groups: _〇_, _χ_, -〇-X_, -N_X_, _s_x_, -X5-, -〇-x5-, -N-X5-, -S -X5-, -〇-χ7_, -〇-C(=〇). . -NH-C(=〇). . .C(=〇)- ' -C(=0)-0- > -C (=0).N. and C(=〇)_x_ ; • X is independently selected from the following groups: none, c(=0), oc(=〇), CH2, CH, S, NH, take 6 and X;, X36 and can be independently selected from the following groups: none, C(〇), C(=S), 0C(=0), CH2, CH, S, Ο, and NR5; and X7 can be independently Selected from the following groups: none, C Bu (7), c (= s), 〇 C (= 〇), ch2, ς: eight ▲ 4 U, S, ο, and Nr5. In certain embodiments, the function 3 of HPP or HPC of an antibacterial or antibacterial agent-related compound carries a structure selected from the group consisting of structural formula FP-1, structural formula Fp. 2, structural formula. FP-3, structural formula FP-4; 65 201143772 Structural Formula FP-5, Structural Formula FP-6, Structural Formula FP-7, Structural Formula FP-8, Structural Formula FP-9, Structural Formula FP-10, Structural Formula FP-11, structural FP-12, structural FP-13, structural FP-14, structural FP-15, structural FP-16, structural FP-17, structural FP-18, structural FP- 19. Structural formula FP-20, structural FP-21, structural FP-22, structural FP-23, structural FP-24, structural FP-25, structural FP-26, structural FP-27, Structural type FP-28, structural type FP-29, structural type FP-30, structural type FP-31, structural type FP-32, structural type FP-33, structural type FP-34, structural type FP-35, structural type FP-36, _ structural FP-37, structural FP-38, structural FP-39, structural FP-40, structural FP-41, structural FP-42, structural FP-43, structural FP -44, Structural FP-45, Structural FP-46, Structural FP-47, Structural FP-48, Structural FP-49 Structural type FP-50, structural type FP-51, structural type FP-52, structural type FP-53, structural type FP-54, structural type FP-55, structural type FP-56, structural type FP-57, structural type FP-58, structural FP-59, structural FP-60, structural FP-6 structural FP-62, structural FP-63, structural FP-64, _ structural FP-65, structural FP -66, structural FP-67, structural FP-68,

W Structural FP-69, Structural FP-70, Structural FP-71, Structural FP-72, Structural FP-73, Structural FP-74, Structural FP-75, Structural FP-76, Structure FP-77, structural FP-78, structural FP-79, structural FP-80, structural FP-8 structural FP-82, structural FP-83, structural FP-84, structural FP -85, structural FP-86, structural FI-1, structural FI-2, structural FI-3, structural FI-4, structural FI-5, structural FI-6, structural FI-7 Structural Formula FI-8, Structural Formula FI-9, Structural Formula FI-10, Structural Formula FI-11, Structural Formula FI-12, Structural Formula FI-13, Structural Formula FI-14, r (66 201143772

Structural FI-i5, structural FI-16, structural FM7, structural FM8, structural FI-i 9, structural FI-20, structural π·2 bu structure fi_22, structural FI-23, structure Formula FI-24, structural formula π_25, structural formula fi_26, structural formula FI-27, structural formula FI-28, structural formula π_29, structural formula Η·%, structural formula FL-3, structural formula FI_32, structural formula FI_33, structure Formula Fs-i, structural formula FS-2, structural formula FS-3, structural formula FS_4, structural formula fs_5, structural formula FS-6, structural formula FS-7, structural formula FS_8, structural formula fs_9, structural formula FS-H ), structural FS-H, structural Fs_12, structural fs_i3, structural FS-14, structural FS-15, structural Fs_16, structural FS_l7, structural FS-! 8, structural FS-19, structure FS_2〇, structural ρτ_ i, structural FT-2, structural FT_3, structural _4, structural ρτ_5, structural FT-6, structural FT-7, structural FT_8, structural FT_9, structure Formula FT-10, structural formula FT_U, structural formula FT_12, structural formula FT_13, structural formula FT-14, structural formula FT-15, and structural formula FT_丨6, as defined above, including stereoisomers and pharmacy Can be accessed The salt to be accepted, wherein: m=〇.1^2>3^4>5^6>7^8^9^10>ll>12^ 13, 14, 15, 16, 17, 18, 19, 20 n = 〇, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, ·.

Ri may be selected from the group consisting of hydrazine, CVCm hydrocarbyl, CVC2. Alkoxy, C丨-C2 nonenyl, CrC20 alkynyl, aryl and heteroaryl; R2 may be selected from the group consisting of hydrazine, Cl_C2 fluorenyl, ci-C2 hydrazine, G-C20 olefin a group, a Cl_C20 alkynyl group, an aryl group and a heteroaryl group;

67 201143772 R3 may be selected from the group consisting of hydrazine, CVC20 hydrocarbyl, CVC20 hydrocarbyloxy, Ci-C2 fluorenyl, Ci-C2 fluorene, aryl and heteroaryl; R_5 and R35 may each independently be selected from the following Group: Η, _c(=0)NH2, CH2CH2OR6, CH2CH2N(CH3)2, CH2CH2N(CH2CH3)2, CH2CH2OR6, cn, F, Br, I, Cl_c2. Hydrocarbyl, Ci_c2G cycloalkyl, CrCw alkoxy, CVC20 cycloalkyloxy, Ci_c2Galkenyl, Ci_c2Q cycloalkenyl, CVC20 cycloalkynyl, CVC20 alkynyl, aryl, heteroaryl, c(=〇)-W and W ; _ R6, 尺 36 and Κ 46 can be independently selected from the following groups: Η, F, C1

Br, I, Na+, Κ+, C(=〇)R5, 2-oxo-1-imidazolidinyl, phenyl, 5-indanyl, 2,3-dihydro-1H-indol-5-yl , 4-hydroxy-1,5-naphthyridin-3-yl, Ci-C12 hydrocarbon group, CVCu cyclic hydrocarbon group, q-Cu alkoxy group, CVCu cycloalkyloxy group, C^-Cp fine group, Ci-C^ ring The dilute group, the Ci-Cu cycloalkynyl group, the Ci-C^ alkynyl group, the aryl group, the heteroaryl group, the c(=0)-w, and the W, R7 and R37 may each independently be selected from the group consisting of η, F, Cl, Br, • 1 , CH3NHC(=0)CH2CH(NHR8)C(=0), R5N=C(NHR6)NHC(=〇)-, C(=0)CH3, C(=0)R6, PO (OR5) OR6, CVC20 hydrocarbyl, CVC20 alkoxy, CVC20 alkenyl, Ci-C20 alkynyl, aryl, heteroaryl, c(=〇)-W, and w;

Rs and R38 may each independently be selected from the group consisting of: 11, 卩, (: Bu; 81·, I, CH3, C2H5, CF3, CH2CH2F, CH2CH2C, CH2CH2Br, CH2CH2I, CH2CHF2, CH2CF3.CH2F, CH2Cn, CH2Br, CH2I, CH2NR6R7, CH(NHR7)CH2C(=0)NH2, C3H7, C4H9, CsH!!, r6, c(=o)r6, c(=o)nh2, ch2c(=o)nh2, ch2oc(=o )nh2 r, ri L bi i 68 201143772 PO(OR5)OR6 ' c(ch3)2c(=o)or6,ch(ch3)c(=o)or6, ch2c(=o)or6,c(=o) -w ; X2 may be selected from the group consisting of: none, H, CH2(CH2)nOR8, Cl, F, Br, I, N02, CN, CF3, C2F5, C3F7, OCF3, OC2F5, NH2, NHR6, CH3, C2H5 , r6, c(=o)nh2, ch2oc(=o)nh2, CH2C(=0)0R5, CH2(CH2)nN(CH3)2, CH2(CH2)nS03R5, hydrocarbon group, CN8 hydrocarbonthio group, cu8 hydrocarbon amino group And a Cu alkoxy group, x3 may be selected from the group consisting of: none, hydrazine, N3, S03W, F, α, Br, • OH, OCH3, OR6, CH3, r6, c(=o)ow, OW and I ; x4 may be selected from the following groups: none, N, CH, and CY1; X5 and X35 may be independently selected from the following groups: none, C(=0), C(=S), 0C(=0), CH2 , CH, S, 0, and NR5; Y1, Y31, Y2, Y32, Y3, and Y4 are independent Selected from the group of 歹丨J: Η, OH, OW, 0C(=0)W, 0C(=0)CH3, CH3, C2H5, C3H7, C4H9, S03R6, CH20R6, CH20C(=0)R6, • CH2C (=0)0R8, OCH3, OC2H5, CH3S02, R6S02, R6S030R6, CH3S03, R6S03, N02, CN, CF3, OCF3, CH=CHC(=0)NHCH2C(=0)0W, CH2(CH2)nNR5R6, CH2( CH2)nOR6, CH(C(=0)NH2)NHR6, CH2C(=0)NH2, F, Br, I and Cl; Z, AA, HA, R, Rs, Y, R11-R16, X, LI, The definitions of L2, L4, L3 1, L32, L34 and W are the same as previously described; and any CH2 group may be substituted by hydrazine, S, N R6 or any pharmaceutically acceptable substituent. 69 201143772 In the present invention, "pharmaceutically acceptable salt" means a salt of a compound of the present invention which can be safely used in an organism. A pharmaceutically acceptable salt includes the presence of the compound of the present invention. a salt of an acidic group or a basic group. Pharmaceutically acceptable acid salts include, but are not limited to, hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, hydrogen sulfate, phosphate, Acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, tartrate, pantothenate, acid tartrate, ascorbate, succinate, maleate, Gentianin_gentisinate, fumarate, gluconate, glucaronate, saccharate, citrate, benzoate, glutamate, sulfonate, ethyl sulfonate An acid salt, a besylate, a p-toluenesulfonate, and a dibasic acid salt (ie: 1,11-methylene-di-(2-hydroxynaphthoate)). Certain of the present invention. The compound can form pharmaceutically acceptable salts with a variety of amino acids. The basic salts include, but are not limited to, aluminum salts, calcium salts, lithium salts, magnesium salts, potassium salts, sodium salts, salt salts, and diethanolamine salts. For a review of pharmaceutically acceptable salts, see BERGE ET AL. 66 J. PHARM. SCI. 1-19 (1977) 'Incorporated herein by reference. In the present invention, unless otherwise indicated, the term "hydrocarbyl" means branched or unbranched, A saturated or unsaturated, monovalent or multivalent hydrocarbon group, including saturated hydrocarbyl, alkenyl and alkynyl groups. Examples of hydrocarbyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl, decyl, decyl, Eleven, didecyl, vinyl, propyl, butenyl, isobutyl, pentyl, hexyl, heptenyl, octenyl, nonenyl, decyl, Eleven carbon base, ten

LS 201143772 dikenyl, ethynyl, propynyl, butynyl, isobutynyl, pentynyl, hexynyl, heptynyl, octynyl, decynyl, decynyl, undecylene Alkynyl, dodecene, methylene, ethylene, propylene, iS0pr0pyiene, butylene, isbutylene , t-butylene, pentyiene, hexylene, heptylene, octylene, nonylene, decylene ), undecylene and dodecylene. In certain embodiments, the hydrocarbon group contains from 1 to 30 carbon atoms. In certain embodiments, the hydrocarbon group contains from 1 to 20 carbon atoms. In certain embodiments, the hydrocarbon group contains from 1 to 12 carbon atoms. In the present invention 'unless otherwise stated, the soil is a hydrocarbon group having at least one ring and no aromatic ring. Examples of cyclonic acid groups include, but = 1 propyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, ring #土, fluorenyl, cyclodecyl, cyclo-indenyl, and ring Second burning base. In some of the St formulas: the hydrocarbon group contains from 1 to 30 carbon atoms. In some formulas, the carbonium group contains from 1 to 20 carbon atoms. In this interesting mode, the hydrocarbon group contains _2 carbon atoms. In the present invention, the term "师_秘 yl)" means a cyclic hydrocarbon group of at least one carbon atom unless otherwise stated. Non-carbon atoms on the ring: children ^ non-oxygen and nitrogen. 4 t is not limited to, sulfur, in the present invention, π does not otherwise specify alkoxyl. This i-S 3 71 201143772 term refers to a nicotinic, cyclic or heterocyclic hydrocarbon group containing one or more oxygen atoms. Examples of alkoxy groups include, but are not limited to, -CH^OH, -〇ch3, -〇-Re, -Re_〇H, -Rel-〇_Re2•, where Re, Rel, and Re2 are the same or different Hydrocarbyl, cycloalkyl or heterocycloalkyl. In the present invention 'unless otherwise stated, 'alkyl halide, the term refers to a hydrocarbon group, a cyclic hydrocarbon group or a heterocyclic ring containing one or more halogen atoms. Hydrocarbyl group. "Halogen, the term refers to fluorine, chlorine, bromine or iodine. Examples of hydrocarbyl groups include, but are not limited to, _Re_F, _Re_a, -Re_Br', _Re(F>, -Re(Cl)-, -Re( Br)· and _Re(I)_, wherein Re is a hydrocarbon group, a cyclic group or a heterocyclic hydrocarbon group. In the present invention, unless otherwise stated, "alkyUhio", the term means containing - or a hydrocarbon group, a cyclic hydrocarbon group or a heterocyclic hydrocarbon group of a plurality of sulfur atoms. Examples of the hydrocarbonthio group include, but are not limited to, _CH2_SH, -π%, _S_Re ' _Re_SH, ·Rel-S-Rer, wherein Re, Rel and Re2 are the same Or a different hydrocarbyl, cycloalkyl or heterocycloalkyl group.

In the present invention, unless otherwise indicated, "alkyamino": a term refers to a hydrocarbon group or a cyclonicotinocyclic hydrocarbon group containing one or more nitrogen atoms. Examples of nicotinamide include, but are not limited to, E. Li, Qing:, ^ 'Re'NH2' " Rel^5. 6 Η α 62 is the same or different hydrocarbyl, cycloalkyl or heterocyclol in the present invention 'unless the term refers to the inclusion of alk-nyl, Λ, s or more carbonyl groups Hydrocarbyl, cycloalkyl, xanthene hydrocarbyl. Hydrocarbon lead | k — 么 'Working for 4 feet of soil, including, but not limited to, aldehyde group 72 201143772 (-Re-C (O)-H), keto group (-Re-C (〇)-Rel), Acid-lowering group (Re_c(=〇)〇H) 'A vine group (-Re-C(=0)0-Rel), amidino group (-Re_c) 〇Ν (υυ, ketene (-Re- C(0)-C(Rel)=C(Re2)Re3), 醯 醯 group (·κ(〇)-Χΐι) and anhydride group (-Re-C(0)-0-C(0)-Rel Wherein Re, Rei, Re2 and Re3 may be the same or different hydrocarbyl, cycloalkyl or heterocycloalkyl. In the present invention 'unless otherwise stated, the term "perfluoroalkyl" means containing one or A hydrocarbon group, a cyclic hydrocarbon group or a heterocyclic hydrocarbon group of a plurality of fluorine groups, including but not limited to, polyfluorodecyl, polyfluorinated fluoroethyl, polyfluoropropyl. In the present invention, unless otherwise specified, ''aryl , the term refers to a chemical structure containing one or more aromatic rings. In certain embodiments, one or more of the atoms on the substrate are non-carbon atoms such as oxygen, nitrogen, or sulfur ("heteroaryl," Examples of aryl groups include, but are not limited to, phenyl, benzyl, naphthyl, anthracenyl Acridinyl, quinolyl, isoquinolyl, π-pyrazinyl, quinoxaliny!, acddinyl, π-decyl, quinoxalinyl, pyridazinyl, Cin 〇 n n cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin cin , isodecyl, thienyl, benzothienyl, oxazolyl, oxazolyl, oxazolyl, benzoxazolyl, isomerism, succinyl, benzoisoindolyl, sinyl (thiax) 〇lyl), fluorenyl and benzo-β-seat. In certain embodiments, the transport unit of hydrazine contains a protonatable amino group, which promotes raft crossing or transport through a layer of "multilayer biological barrier (eg, ratio The parent drug is at least about 20 times, about 50 times, about 1 times, about 3 times, 73 201143772 about 500 times, about 1000 times faster. In certain embodiments, the protonatable amino group is at physiological pH The time is substantially protonated. In certain embodiments, the protonation of the amino group is reversible. In certain embodiments, the transport unit is passed at Hpp - The layer or layers of the biological barrier may or may not be resolved. In certain embodiments, the functional unit may contain a transport agent for the antimicrobial compound and the antimicrobial-related compound having at least one free amino group for 3 "In certain embodiments, the protonatable amino group is selected from the group consisting of: a taxically acceptable substituted and unsubstituted primary amino group, a pharmaceutically acceptable substituted and unsubstituted secondary amino group, and a pharmaceutically acceptable Substituted and unsubstituted tertiary amino groups. In certain embodiments, the protonatable amino group is selected from the group consisting of: construction W-Bu structure W-2, structure cut _3, structural formula w_4, structural formula W-5, structural formula W_6, structure Formula w_7, structural formula w_8, structural formula (four), structural formula wu), structural formula w_n, structural formula w_12, structural formula m, f-configuration W_14, structural formula w-15, structural formula W_!6, structural formula (IV) and: The configuration MM8' has the same definition as previously described, including stereoisomers and pharmaceutically acceptable salts thereof. In certain embodiments, the functional unit and transport unit=ligand that link Hpp contain a cleavable bond that can be cleaved after HPP has permeated one or more layers of the biological barrier, including, for example, covalent bonds, Junction bonds, sulfur, Amine amine bond, cool bond, sulfur vinegar bond 'carbonate vinegar bond, carbamate bond, phosphate bond or hydrazine bond. In certain embodiments, the "201143772 HPP of the antibacterial or antibacterial-related compound has the structure of the following structural formula L-1:

U Λ Structural Formula L-1 includes stereoisomers and pharmaceutically acceptable salts thereof. F is a functional unit of HPP of an antibacterial or antibacterial-related compound. Examples of F include structural formula F-1, structural formula FP-1, structural formula FP-2, structural formula FP-3, structural formula FP-4, structural formula FP-5, structural formula FP-6, structural formula FP- 7. Structural formula FP-8, structural FP-9, structural FP-10, structural FP-11, structural FP-12, structural FP-13, structural FP-14, structural FP-15, Structural formula FP-16, structural FP-17, structural FP-18, structural FP-19, structural FP-20, structural FP-2, structural FP-22, structural FP-23, structural formula FP-24, structural FP-25, structural FP-26, structural FP-27, structural FP-28, structural FP-29, structural FP-30, structural FP-3 structural FP- 32. Structural FP-33, structural FP-34, structural FP-35, structural FP-36, structural FP-37, structural FP-38, structural FP-39, structural FP-40, Structural type FP-4 Bu structural type FP-42, structural type FP-43, structural type FP-44, structural type FP-45, structural type FP-46, structural type FP-47, structural type FP-48, structural type FP-49, structural FP-50, structural FP-51, structural FP-52, structural FP-53, structural FP-54, structural FP-55, structural FP-56, structural FP- 57 Structural type FP-58, structural type FP-59, structural type FP-60, structural type FP-6, structural type FP-62, structural type FP-63, structural type FP-64, structural type FP-65, structural type FP-66, structural FP-67, structural FP-68, structural FP-69, structural FP-70 八75 201143772 Structural FP-71, structural Fp_72, structural Fp_73, structural Fp_74, structural formula FP-75, structural Fp_76, structural Fp-77, structural Fp_78, structural formula FP_79, structural formula Fp_8〇, structural formula Fp_8i, structural formula π. structural formula FP-83, structural formula Fp_84, structural formula Fp_85, structure Formula a%, ,. Construction FI 1, .,. Configuration FI_2, structural formula fi·3, structural formula η·4, structural formula FI 5, 'σ configuration FI_6, structural formula FI 7, structural formula m, structural formula F!-9, structural FM〇, structure FI U, structural FI12, structural FI]3, structural FI_14, structural formula 5, structural fi i6, structural FI-17, structural FI-18, structural Fi-i9, structural fi] (7) Construction FI-21 'Structure type FI_22, structural formula, structural formula, structural formula FI-25, structural formula FI_26, structural formula 、27, structural formula Η], structural formula FI-29, structural formula FI_3〇, structure Formula fi_3, structural formula FI_33, structural formula FS-1, structural formula FS_2, structural formula FS_3, structural formula FS-4, structural formula FS_5, structural formula fs_6, structural formula π. Structural formula FS-8, structural formula FS_9, structural formula Fsi(), structural formula (1), structural formula FH2, structural formula FS_n, structural formula Fs]4, structural formula fs_i5, structural formula FH6, structural formula FS_17, structural formula Fs_i8, structural formula fs_i9, structural formula FS-20, structural formula", structural formula ρτ_2, structural formula π", structural formula FT-4, structural formula FT_5, structural formula ft_6, structural formula π.钇 FT-8, structural FT_9, structural FT_1〇, structural pm, structural FT-12, structural FT_U, structural FT_14, structural π·. And the structural formula FT-b, the definition of which is as described above; τ is the transport unit of the HPP of the antibacterial or antibacterial agent-related compound. For example, T can be selected from the group consisting of protonizable nitrogen, pharmaceutically acceptable, and unsubstituted amino-amino, pharmaceutically acceptable substituted and unsubstituted secondary amino groups, and pharmaceutically acceptable Substituted and unsubstituted tertiary amino group, structural formula W-1, structural formula W-2, structural formula w_3, structural formula w_4, structural formula W-5, structural formula W-6, structural formula w_?, structural formula w_8, Structural structural formula W-12, structural formula W-9, structural formula W-10, structural formula w_u W-13, structural formula W-14, structural formula cooked 15, structural formula w_16, structural formula W-17 and structural formula W-18, whose definition is as described above;

The definitions of Lj L31 2 L32, L4 and ;l34 are as described above. In certain embodiments, and -l3i-l34-L32- are independently selected from the group consisting of -Ο-, -X-, -〇_x_, N x, _s x, _Χ5, 〇_Χ5, respectively. -Ν-χ5-, -S-X5-, ·〇-χ7_,_0_c〇), ΝΗ c(=〇), c(=〇)_, -C(=〇)-〇-, -C(= 0) -N- and -C(=〇) x_, where χ, & and χ7 are as defined above. In certain embodiments, the hydrazine or HPC of the antimicrobial or antimicrobial related compound comprises a structure selected from the group consisting of structural formula ρ1, structural formula P-2, structural formula P-3, structural formula p_4, structural formula P_5, structural formula p_6, structural formula P-7, structural formula P-8, structural formula p_9, structural formula p_1〇, structural formula P-11, structural formula P-12, structural formula p_13, structural formula p-14, structure Formula p_15, structural formula P-16, structural formula Ρ_π, structural formula p_l8, structural formula p_19, structural formula P-20, structural formula P-21, structural formula p_22, structure sp_23, structural formula P-24, structural formula P- 25. Structural formula p_26, structural formula p_27, structural formula P-28, structural formula P-29, structural formula p_3〇, structural formula m, structural formula p_32, structural formula P-33, structural formula ρ·34, structural formula %, structure sp_36, structural formula P-37, structural formula P-38, structural formula p_39, structural formula p_4〇, structure (5) 77 201143772 Formula P-41, structural formula P-42, structural formula P-43, structural formula P -44, structural formula P-45, structural formula P-46, structural formula P-47, structural formula P-48, structural formula P-49, structural formula P-50, structural formula P-51, structural formula P-52 , structural formula P-53, structural formula P -54, structural P-55, structural P-56, structural P-57, structural P-58, structural P-59, structural P-60, structural P-61, structural P-62 Structural formula P-63, structural formula P-64, structural formula P-65, structural formula P-66, structural formula P-67, structural formula P-68, structural formula P-69, structural formula P-70, structure P-71, structural P-72, structural P-73, structural P-74, structural climbing P-75, structural P-76, structural P-77, structural P-78, structural P-79, structural P-80, structural P-81, structural P-82, structural P-83, structural P-84, structural P-85, structural P-86, structural formula 1- 1. Structural formula 1-2, structural formula 1-3, structural formula 1-4, structural formula 1-5, structural formula 1-6, structural formula 1-7, structural formula 1-8, structural formula 1-9, Structural formula 1-10, structural formula 1-1-1, structural formula 1-12, structural formula 1-13, structural formula 1-14, structural formula 1-15, structural formula 1-16, structural formula 1-17, structural formula 1-18, structural formula 1-19, structural formula 1-20, | structural formula 1-21, structural formula 1-22, structural formula 1-23, structural formula 1-24, structural formula 1-25, structural formula 1 -26, structural formula 1-27, structural formula 1-28, structural formula 1-29, structural formula 1-30, structural formula 1-31, structural formula 1-32, structural formula 1-33, structural formula S-1, structural formula S-2, structural formula S-3, structural formula S-4, structural formula S- 5. Structural formula S-6, structural formula S-7, structural formula S-8, structural formula S-9, structural formula S-10, structural formula SU, structural formula S-12, structural formula S-13, structural formula S-14, structural formula S-15, structural formula S-16, structural formula S-17, structural formula S-18, structural formula S-19, structural formula S-20, structural formula T-1, structural formula T- 2. Structural formula T-3, structural formula T-4, structural formula T-5, structural formula T-6, structural formula T-7, rotary r, i.3 i 78 201143772 Construction Τ-8, structural Τ -9, structural formula Τ-10, structural formula T-ll, structural formula T-12, structural formula T-13, structural formula T-14, structural formula T-15, and structural formula Τ-16:

Structural formula P-ι Structural formula Ρ-2

Structural Ρ-3

Structure Ρ-5 Structure Ρ-4

79 201143772

Structural formula P-9 Structural formula P-10

Structural formula p-ll Structural formula P-12

80 201143772

Structural formula P-15 Structural formula P-16

Structural formula P-18 Structural formula P-17

Structural formula P-20 Structural formula P-19

81 201143772 Structural formula P-21 Structural formula P-22

Structural formula P-23 Structural formula P-24

Structural formula P-25 Structural formula P-26

Structural formula P-28 Structural formula P-27

SI SI 82 201143772

Structural formula P-29

Structural P-33 Structural P-34

Structural P-35 Structural Formula P-36 83 201143772

Ό—Re

Structural P-37 Structural P-38

Structural P-39 Structural Formula P-40

严 Ο-Re Structure P-41 Structure P-42

HA H^l

\

\^N Structure P-43 Structure P-44 84 201143772

Structural P-45 Structural P-46

Structural formula P-49 Structural formula P-50

Structural formula P-51 Structural formula P-52 85 201143772

Structural formula P-53

Structural formula P-54

Structural formula P-56

Structural P-57 Structural Formula P-58

Structural formula P-59 Structural formula P-60 86 201143772

Structural formula P-62

Structural P-64 Structural P-64

Structural formula P-65 Structural formula P-66 87 201143772

Structural P-67 Structural P-68

Structural formula P-71 Structural formula P-72 88 201143772

Structural P-73 Structural P-74

Structural P-75 Structural Formula P-76

Structural formula P-77 Structural formula P-78 89 201143772

Structural P-79 Structural P-80

N I Structural P-81 Structural P-82

Structural P-83 Structural Formula P-84

w 90 201143772 Structural Ρ-85

^I^ Structure Ρ-86

X Structural formula 1-2 Structural formula 1_ Structural formula

◊ Y2 η2 Ο person /. Ο Ν

Structural formula 1-4 \ '0 person N gossip. , H II structural formula Ι·

丫2

Structural Formula I" Structural Formula 1-6

Structural formula 1-8 Υι

Y2

Structural formula 1-9 91 201143772

Structural Formula I-10 Structural Formula I-11

Structural formula 1-15

Structural formula 1-14

Structure 1-16 Structure 1-17

92 201143772 Structure 1-19 Structure 1-18

•Y4

-Y4 Structure 1-20

Structural formula 1-21

Structure 1-23 Structure 1-22

丫4 Structure 1-24

Structure 1-25

Structure 1-27 Structure 1-26 93 201143772

Structure 1-28 Structure 1-29

Structural formula 1-30 Structural formula 1-31

Structural formula 1-32 Structural formula 1-33

Structural formula S-1 Structural formula S-2

94 201143772 Structural S-3 Structural S-4

Hz

Xs

Structural formula S-6

, Xs,

Structural formula S-8 Structural formula S-7

Structural formula S-9 Structural formula S-10

r* j s 95 201143772 Structural formula S-11 Structural formula S-12 Structural formula S-13

Structural formula S-14 Structural formula S-15 Structural formula S-16

Structural formula S-17

Structural formula S-18

Structural formula S-19 Structural formula S-20

Structural Τ-l Structural Τ-2 Structural Τ-3 96 201143772

Υ4 Structure Τ-4 Structure Τ-5 Structure Τ-6

Structural Τ-9 Structural Τ-1 0 97 201143772

Structure Τ-11 Structure τ-12 Structure Τ-13

^T~14 Structural formula T-15 The structural formula Τ-16, includes its stereoisomers and pharmaceutically acceptable salts, wherein: m, n, R, R2, R5, R τ» η \35, R6, R36, R46, r7, r8, R38, τ, W, χ, X2, X4, X5, X35, X6, X36, X46, X7, 丫丨, Y2, Y31, Y32, Y, Y, 7 3 4 The definitions of , , AA, HA, R, Rs, and Rn-R16 are as described above.

Pharmaceutical group of ιι» Another aspect of the invention relates to a pharmaceutical composition comprising at least one antibacterial or antibacterial agent-related compound HPP, and a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable: der" as used herein refers to a pharmaceutically acceptable material, composition or medium such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. It participates in the transfer of an HPP from a position and body of the body; night, [S3 98 201143772 "(inside.p or outside), or transporting, body fluids, tissues, and carriers to another part of the body." (internal or external), or part. For pharmaceutically acceptable, i.e. fiPP/ilPC compatible, daily, * ra /, other ingredients in the table, such as excessive toxicity of the helmet, born in tissues or organs that contact a biological system 'U (four) read, irritating, Problems or complications and complications: immunogenicity, or other ratios of risk/risk that can be used as a remedy. Materials that are acceptable as a carrier for fungi such as lactose, glucose and axe. 1) saccharides, powders; 3) fibers (4): b) (iv) classes such as corn porridge and potato-based cellulose and acid fiber m ^ Μ Cellulose sodium salt, B'., '4' powdered yellow enamel brand. Shuang note. <, gelatin; 7) talcum powder; 8) L 耋, 5) wheat teeth, 6) such as peanut oil, cottonseed Oil = two;: oil and suppository ants; 9) oil, soybean oil; 10) glycols: socks, oil, corn oil and other types, such as glycerin, mountain polyethyl oleate and bismuth社纯畔' 12) From the Japanese category, such as _ such as chlorine oxidation, the purpose; 13) fat filling; 14) buffers, 1 7) isotonic water.] ... ^ hot raw water, alcohol. 2 diit Solution; 19) alcohols, such as ethanol and propanol, 20) non-toxic compatible substances for phosphate buffer solutions, such as two and 21) other pharmaceutical preparations should be included in the pharmaceutical preparations Pharmaceutically acceptable auxiliary substances, such as pH adjusting and buffering agents, for example, acetic acid (iv) and its analogs, potassium telluride, calcium calcium, sodium lactate and the like. In one embodiment, the pharmaceutically acceptable carrier is an aqueous carrier S3 99 201143772 such as a buffered saline solution and the like. In a peptide embodiment φ^r-, τ, the acceptable carrier is a polar solvent such as acetone and alcohol. In these formulations, the concentration of strontium can vary widely, depending on the particular mode of administration chosen and the needs of the biological system, based primarily on fluid = product, viscosity, body weight, and similar parameters. For example, the concentration (= weight) may be 0.0001% to 100%, 〇 001 % to 50%, 〇 % to 30%, 0.1% to 20%, 1% to 1%.

The compositions of the present invention can be administered for prophylactic, therapeutic, and/or healthful use by administration. Such administration can be by topical, mucosal administration, such as oral ', 'nasal, vaginal, rectal, non-oral, transdermal, subcutaneous, intramuscular, intravenous, inhaled, ocular Administration and other conventional routes. The pharmaceutical composition can be administered in a variety of unit dosage forms in a unit dosage form such as a powder, a dose, a capsule, and a lozenge. The unit dosage forms that are suitable for transdermal delivery, such as solutions, suspensions and gels, are extracted from _ 曰. Thus, a typical pharmaceutical composition for intravenous administration can be (4) (10) grams, about gram to about gram, about G gram to gram, about 0.01 gram to about 10 grams, or about gram to about 1 gram. The actual daily dosage of each administered organism can range from about _mg to about gram of the orally administrable θ composition is well known in the art or will be apparent to those skilled in the art, and in the publication Such as Remington's Pharmaceutical Science, i cfi ” e., Mack Publishing Company, Easton, Pa (1980). There is more... + Description of the cover. 100 201143772 ill. HPP, & 〇 method for infiltrating biological barriers Another composition of the present invention, the layer of the layer or the layer of the biofilm, the composition of the invention is osmotically administered to sputum or anti The ___ ^ = method includes steps for the organism. In some implementations 胄化 &, or its combination of drugs =:::=:r2 ❹ times... one: 1 _ times or more, about _ times or by. On; ^Up, about (10) times or more, about or P-door:: thick bioscreen P early" means separating an environment into different spatial regions == layer This separation can be regulated (eg, constraints, limits, H) Substanee or material-warfare: the passage, penetration or translocation of a zone to another compartment/area. The different spatial zones or compartments of this "t may have the same or different chemical neoplasmic environments. The biological layers mentioned include, but are not limited to, the raw surface, the biological structure of the cell layer, the biological object, the inner surface of the organism or organ or body cavity, the outer surface of the object, organism, organ or body cavity, or Any combination of biological membranes, such as lipid bilayer structure, eukaryotic cell membrane, prokaryotic cell membrane, and intracellular membrane (eg, nuclear membrane or organelle, such as Golgi 2 membrane or envelope, coarse Membrane or envelope of the surface and smooth endoplasmic reticulum (ER), membrane or envelope of ribose limb, membrane or envelope of vacuole, membrane or envelope of vesicle, membrane or envelope of liposome, membrane of mitochondria Or envelope, lysosomal membrane or envelope, membrane of the nucleus or Membrane, chloroplast membrane or envelope, plastid 1 L i 101 201143772 = or envelope, peroxidase membrane or envelope, or micro-membrane or packaged in this lipid bilayer structure A bilayer structure of a lipid molecule, including but not limited to, scale fat and cholesterol. In a particular embodiment, the bilayer, sister lipid is composed of a polar head group and a non-polar fatty acid tail group. The two-layer structure consists of two layers of lipids arranged in such a way that their carbon-gas tails face each other and form an oily core by hydrophobic interaction, while their charged head groups are oriented towards the aqueous solution on either side of the membrane. In another specific embodiment, the lipid bilayer structure may contain one or more intercalating proteins and/or sugar molecules. Examples of cell layers include eukaryotic cell layers (eg, epithelium, lamina propria, and smooth muscle). Or mucosal muscle layer (in the gastrointestinal nucleus cell layer (eg, surface layer or s layer, ^ two-dimensional structure monolayer composed of the same protein or glycoprotein, in particular, s layer refers to a part usually present in bacteria and archaea (archaea) cell Membrane), a biofilm (a structured microbial community encapsulated in a self-developing polymeric matrix that adheres to a biological or inert surface), and a plant cell layer (eg, epidermis). The cell can lick normal cells or pathology Cells (eg, diseased cells, cancer cells). Examples of biological structures include structures that are sealed by tight junctions or closed junctions, which provide barriers to the entry of toxins, bacteria and viruses, such as the blood-milk barrier and the blood-brain barrier. (bl〇〇d brain barrier, BBB). In particular, BBB consists of a class of non-permeable endothelium, which appears to form a physical barrier by tight junctions that bind adjacent endothelial cells, and also appears to be a transport of efflux transport pumps. Barriers. Biological structures can also include cells, proteins, and glycocalyx "10) 102 201143772 A mixture of classes (such as thrombus). Examples of the inner surface of a biological object, organism, organ or body cavity include buccal mucosa, esophageal membrane, gastric mucosa, intestinal mucosa, mucosa, oral mucosa, bronchial mucosa, uterine mucosa, and endometrium (' The station membrane of the subunit 5, the inner layer of the cell wall of the pollen grains, or the inner wall of the spore), or a combination or plural thereof. Examples of external surfaces of biological objects, organisms, consultants, or body cavities include capillary a tubes (eg, capillaries of cardiac tissue), membranes of the membrane attached to the skin (eg, in the nostrils, lips, ears, genital area, and Anal (1), device (4) eve: surface (eg, liver, lung, stomach, brain, kidney, heart, ear, eye: nose, mouth, tongue, colon, pancreas, gallbladder, duodenum, rectum, stomach, large intestine (C〇 1〇nrectum), intestinal, venous, respiratory, vascular, and anorectal), the stratum corneum of the stomach (eg, the dead cell layer of epithelial cells or keratinocytes or the superficial layer of overlapping cells covering the hair shaft of animal hair) (superficial 丨ayer), multi-layered structure on the outer side of the invertebrate epidermis, plant horny layer or polymer cutin and/or cutan), outer layer of pollen grains, or outer wall of spores, And a combination or plural thereof. In addition, the biological barrier further comprises a carbohydrate layer, a protein layer or any/the other biological layer 'or a combination or plural thereof. For example, the skin is a biological barrier having a plurality of biological layers. Contains an epithelial layer (outer surface), a cortex, and an inferior layer. The epithelial layer contains a multi-layered structure including a basal cell layer, a spinous cell layer, a granule cell layer, and keratinocytes called keratinocytes. Angle: ^ Mussel The layer (also called "horny layer") is the outermost layer of the epithelium where the cells are flat and shaped like scales. L >3 i 103 201143772. These cells contain a large amount of keratin, arranged in multiple layers. The skin surface has toughness, oil repellency and water repellency.(4) Method for diagnosing a symptom in a biological system Another aspect of the invention relates to a method for diagnosing a symptom in a biological system using the composition of the invention. The method comprises the steps of: 1) administering Hpp containing an antibacterial agent or an antibacterial agent-related compound to a biological object;

2) detecting the presence, location or content of the Ηρρ, the functional unit of the Ηρρ or its metabolite in the organism; and 3) determining the symptoms in the organism. In certain embodiments, ΗΡΡ (or a cleavage cleavage agent from Ηρρ) accumulates at the site of action where the symptoms occur. In certain embodiments, the presence, location, or amount of functional units of the ticks are also detected. In some practical ways, 'the occurrence and progression of related symptoms (eg, infection) is also measured. In some embodiments, the agent is labeled with a detectable agent or is prepared to contain a radioisotope for detection. The detectable agents are available in the following categories: 0) radioisotopes, such as 35S, 14 (:, 13c, ^, 1251 3 and I. Diagnostic agents can be radioisotopes by techniques well known in the art Marking, radioactivity can be determined by the special method; in addition, for carbon and nitrogen labeling, the diagnostic substance can be detected by spin-electron paramagnetic resonance. Τ'7 104 201143772 (b) Camp light substances such as BODIPY, B〇DIpY , rare earth complexes (铕 chelates), luciferin and its derivatives, mc, 5,6 fluorenyl fluorescein, rhodamine and its derivatives, danshen, lissamine (L1SSamine), algae Red protein, green fluorescent protein yellow fluorescent protein, red fluorescent protein and Texas Red. Fluorescence can be quantified by fluorometer. (0 various enzyme-substrate agents, such as luciferase (such as , firefly luciferase and bacterial luciferase), luciferin, 2,3·dihydro ugly •: 酉 similar (2,3_dihydr〇Phthalazinedi〇nes), malate dehydrogenase, urease, Peroxidase such as horseradish peroxidase (HRPO), test phosphate G enzyme, lactose , glucoamylase, lysozyme, polysaccharide oxidase (sacchaHde) (eg, glucose oxidase, galactose oxidase and glucose-6-phosphate dehydrogenase), heterocyclic oxidase (such as uricase and xanthine oxidase) ), lactose peroxidase, microperoxidase, and its analogs. Enzyme-substrate combinations include, for example, (1) horseradish peroxidase (HRp〇) and peroxidation as a substrate Hydrogenase, in which catalase oxidizes dye precursors (eg, o-phenylenediamine ((10)) $ 3,3,,5,5,·tetramethylbenzidine hydrochloride (TMB); (ii) alkaline Phosphatase (Ap) with p-nitrophenyl phosphate as a chromogenic substrate; (iii) p_D_galactosidase (β-D-Gal) and chromogenic substrate (eg, p-nitrophenyl) Lactosylase) or a fluorogenic substrate 4-methylumbelliferyl_p_D_galact〇side. r r. *1 I jj 105 201143772 In certain embodiments, detectable The substance must be conjugated to the diagnostic substance, but the presence of the diagnostic substance can be identified and the diagnostic agent is measurable. In certain embodiments, the present invention The HPP can be provided by means of a kit, ie, a packaged implant of a predetermined amount of reagent with a diagnostic assay. When labeled with an enzyme, the kit can include a substrate and the help factor (eg, available) The chromogenic group or the substrate of the glory group can be detected. In addition, other added hydrazines such as stabilizers, buffers (e.g., liquid or lysis buffer) and the like can be included. A variety of reactions can be varied widely to provide the need to fully optimize the sensitivity of multiple (four) degrees. In particular, the agent may dry a dry form of powdered formability, which comprises a method of imparting a solution to a desired characteristic of a selected material upon dispersion, and a further aspect of the invention relates to Filtered by characteristics • In some embodiments, the method comprises: covalently connecting the test functional unit to the transport unit via a linker to form a test composition (or covalently linking the functional unit through the linker 2) 3) ^ to test (four) to send the unit 'or covalently connect the functional unit to the transport unit); ^ to administer the test composition to the biological system; and to test whether the test composition has the desired properties or characteristics. Features required for the function may include, for example, . The ability to test an early interpenetrating composition or to convert back to a parent drug, [S j 106 201143772 2) to test the permeability and/or speed of the composition; 3) to test the efficiency and/or effect of the composition; Test the transport capacity of the transport unit; and 5) test the cleavage of the linker. /v) Method for treating a certain condition of an organism / Another aspect of the invention relates to a method of using the composition of the present invention for the treatment of a certain symptom of a biological system. The method comprises administering the pharmaceutical composition to the biological system. The term ''treating, in the context of the present invention, refers to healing, alleviating, inhibiting or preventing. The term "tresat (t r e a t ), in the context of the present invention, refers to healing, alleviating, inhibiting, or preventing. The term "treatment," is healing, alleviating, inhibiting, or preventing. The term "biological system," "organism," or "biological object," in the context of the present invention, refers to an organ, a group of organs that work together to accomplish a task, a living organism, or a group of organisms. The term "organism", in the context of the present invention, refers to a collection of molecules which more or less function as a stable whole and have life properties such as animals, plants, fungi, or microorganisms. The term "animal, in the context of the present invention A eukaryotic organism characterized by active activities. Examples of animals include, but are not limited to, vertebrates (eg, humans, mammals 'reptiles, amphibians, fish, scorpions, narrows ~ 'Oganocardia)), tunicates (eg, sea otters, tails) Ascidians, deep sea squirts, ascidi 〇 a (ascidi 〇 a ) 、 、 、 、 、 、 、 、 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( 'Oka and animal', Cyclosporin () anarthropoda, and heminthes (eg, rotifer). 107 201143772 The term "plant" in the present invention refers to an organism belonging to the plant kingdom. Examples of plants include, but are not limited to, seed plants, bryophytes, ferns, and fern plants. Examples of seed plants include, but are not limited to, cycads, ginkgo, c〇nifers For example, gnetophytes, angiosperms, and examples of bryophytes include, but are not limited to, liverworts, hornworts, and mosses. Examples of ferns include, but are not limited to, bottle sage (〇phi Gl〇ssales) (eg, adders-t〇ngues, genus fern, grape-ferns), pterygium and sacred fern (iept〇sp_fine e ferns) Examples of plants to be quasi-strict include, but are not limited to, 'stone pines (eg, stone pines, cypresses (Spikem〇sses), and water (quillw〇ns)), pine leaf ferns (eg, stone pine plant doors and In the present invention, it refers to a eukaryotic organism belonging to a member of the fungus community. Examples of fungi include, but are not limited to, chytrid, blast 〇clad_yc〇ta, neoca^^. Τ. From the organism in the present invention refers to a microscope visible organism: , = on the micron scale). Examples of microorganisms include, but are not limited to, fine mites, straight ψ ψ Λ ', living organisms, and microscopically visible plants (eg, A and microscopically visible animals (eg, plankton, three intestinal worms, and treatments;某些 〜 〜 某些 疗 疗 疗 疗 疗 某些 某些 某些 某些 某些 某些 某些 某些 某些 某些 某些 某些 某些 某些 某些 某些 某些 某些 某些 108 108 108 108 108 108 108 108 108 108 108 108 108 108 108 2011 2011 2011 108 108 108 108 108 Or HPP' of an antibacterial agent-related compound or a pharmaceutical composition thereof for treating symptoms in a biological system or organism. The method by administering Hpp to an antibacterial or antibacterial-related compound to the biological system or organism, or A pharmaceutical composition thereof. Antibacterial know-how and antibiotic-related compounds can be used to widely regulate a variety of biological processes in biological systems. Symptoms associated with these biological processes can be treated by corresponding antibacterial or antibacterial-related compounds, and thus can also be antibacterial Agent or antibiotic-related compound of ΗΡΡ*Hpc, or a pharmaceutical composition thereof. The symptoms include, but are not limited to, pain, damage Microbial-related symptoms. Microorganism-related symptoms are symptoms caused by microorganisms such as bacteria, fungi, protists, and viruses. For example, symptoms caused by bacteria (bacteria-related symptoms), symptoms caused by protists (native) Symptoms of biological phase) 'symptoms caused by fungi (fungi-related symptoms), and symptoms caused by viruses (virus-related symptoms). Bacterial-related symptoms include, for example, infection (eg infection of an organ) Such as liver, lung, stomach, brain, kidney, heart, ear, eye, nose, mouth, tongue, colon, membrane gland, gallbladder, ten's finger, rectum stomach, colorectal, intestine, vein, Respiratory system, vasculature, anorectal and anal pruritus, respiratory infection, upper respiratory tract infection, urinary tract infection, nosocomial infection, pseudomonas infection, coagulase-positive staphylococcal infection (eg skin infection, poisoning, acute infection) Endocarditis, septicemia, necrotizing pneumonia) \ 〇 〇 109 201143772 Post-prosthesis infection, with sepsis and pneumonia ❹), plague (eg lymphatic plague and pneumonia plague), anthrax (such as · skin charcoal, lung anthrax and gastrointestinal anthrax), Lyme disease, brucellosis, whooping cough, acute enteritis, respiratory tract Sense $, parrot fever, non-gonococcal urethritis, trachoma, neonatal inclusion body conjunctivitis, sexually recorded granuloma, false bribery colitis, gas gangrene: food poisoning, anaerobic cellulitis, diphtheria, Disease, neonatal < month capsule XA blood stasis knot inflammation, hemolytic uremic thin syndrome, rabbit fever,

Pneumonia, bronchitis, gastric ulcer, Legionnaires' disease, Pontiac fever, cephalopodosis, Lee's disease I, leprosy, tuberculosis, mycoplasma pneumonia, gonorrhea neonatal eye k, septic arthritis, epidemic Meningitis, Hua-Fei's syndrome (acute fulminant meningococcal bacteremia), Luoshanshan spot heat, typhoid fever type salmonellosis (typh〇id fever (eight)

Sal_eU〇sis), salmonellosis with gastroenteritis and colitis, bacterial dysentery/bacilli dysentery, cystitis, meningitis and septicemia, endometrial acupoints, otitis media, #sinusitis, syphilis, necrotic tendons Membrane, streptococcal pharyngitis, red fever, rheumatic fever, impetigo, erysipelas, calving fever and cholera. Symptoms associated with protists include, for example, cancer, sleeping sickness, and toxoplasmosis. + fungal-related symptoms include, for example, aspergillosis, blastomycosis, rickets, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, Brazilian bud disease, sporotrichosis, and joints Bacterial disease. Symptoms associated with the virus include, for example, virus-related symptoms including, for example, influenza, yellow fever, and AIDS. In certain embodiments, antibacterial agents or antibacterial agents are available in the organism t 110 201143772

HPP, or a pharmaceutical composition thereof. The method of delaying the treatment of the team includes administering the antibacterial or antibacterial agent to the HPP or its pharmaceutical composition through any field.

The eyes, lungs, and subcutaneous are administered by various unit dosage forms depending on the mode of administration. These include, but are not limited to, oral, enteral, buccal, vaginal, aerosol, transmucosal, transdermal, epithelial, and/or parenteral administration. The parenteral administration of the pharmaceutical composition refers to a route of administration generally associated with injection, including but not limited to intravenous, intramuscular, intraarterial, intrathoracic, intracapsular,

Intravenous injection and / or infusion. The HPP or a pharmaceutical composition thereof can be administered to an organism in the form of a preparation suitable for various administration routes. Formulations useful in the methods of the invention include one or more HPPs, one or more pharmaceutically acceptable carriers, and optionally other therapeutic agent components. The preparation may conveniently be presented in unit dosage form and may be prepared by any methods known in the art. The amount of active ingredient that can be combined with the carrier materials to produce a single dosage form will vary depending upon the organ to be treated and the particular mode of administration. The amount of HPP that can be combined with the carrier material to produce a single dose form will generally be the amount of hpp that produces a therapeutic effect. Typically in the percentage 'the amount ranges from about 1% to about 99% HPP, preferably from about 1 〇/〇 to about 20%. Methods of preparing these formulations or compositions include the step of combining HPP with one or f 111 201143772 accommodating carrier, and optionally one or more accessory ingredients. The preparation is usually prepared by intimately combining HPP with a liquid carrier, or a finely divided solid carrier, or both carriers, and then shaping the product if necessary. The dosage form suitable for oral administration may be a capsule or a cachet.

(aChetS) pills, tablets, keys (1〇zenges) (using a flavoring base, usually sucrose with gum arabic or tragacanth), powders, granules, or solutions or blends in aqueous or non-aqueous liquids t _, or oil-in-water or water-in-oil liquid emulsions, cuts or syrups, or pasties (using inert matrices such as gelatin and glycerin, or residual gum arabic) and/or bismuth: agents and analogues They each contain a predetermined amount of Hpp as an active knives compound and can also be administered by bolus, eiectuary, or bismuth. In oral solid dosage forms (eg, capsules, tablets, pills, dragees, powders, granules, and the like), the HPP is mixed with a carrier of one or more pharmaceutically acceptable ingredients, such as sodium citrate or dicalcium phosphate, and / or any of the following options + (1) fillers or supplements, such as starch, lactose, sucrose, glucose, glycerol, and / or citric acid; (2) binders, for example, carboxymethyl cellulose, bath Acid, gelatin, polyvinylpyrrolidone, sucrose, and/or gum arabic; (3) humectants, such as glycerol; (4) cleavage agents, such as agar, calcium carbonate, horse yam or tapioca, alginic acid , certain citrates, with sodium carbonate, (5) solution blockers, such as paraffin, (6) absorption accelerators, such as quaternary ammonium compounds; (7) humidifying agents, such as 'acetol and mono-hard fat Acid glycerides; (8) absorbents such as kaolin and bentonite; (9) lubricants such as talc, calcium stearate, 112 201143772::di, ethylene glycol, sodium lauryl sulfate, and mixtures thereof; ) color toner. In the case of capsules, tablets and pills, the substance may also contain a buffer. Solid compositions of a similar type are also used as fillers in soft and hard filled gelatin capsules using such excipients as lactose or nougat, as well as polymers: 7 alcohols and the like; The method of the mold is prepared by selectively using the second aid component. Compressed tablets can be used in "salt", for example, to solve two-dimensional substances, lubricants, inert diluents, preservatives, (for example, by acetaminophen (s〇dium with one (6):, τ:Iΐ fiber) Preparation of sodium or a surface active or dispersing agent. Molding can be carried out in a suitable machine by compressing a mixture of a powdered antibacterial agent or a peptide-like liquid diluent, such as a sugar-coated pill. Capsules, pills and granules, 2 shells are scoreed or prepared, such as enteric coatings and other coatings well known in the art. They can also be formulated to provide HPP retardation, for example, using multiple ratios of propylated The base cellulose and thus the release curve 'use other polymer matrices, using liposomal probiotic B. They can be sterilized by, for example, bacterial trapping of the diaphragm, or by adding a sterilizing agent to the mixture and the compound. : Immediately dissolved in sterile water, or other sterile injectable media, these compositions may also optionally contain paclfylng agents' and may selectively release HPP at specific sites of the delayed gastrointestinal tract. Group Examples thereof 113201143772 ... package include polymeric substances and waxes may also be .HPP the form of microcapsules, where appropriate also with - one or more of the above-described excipients.

Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, dispersions, and HPPs, which may contain inert diluents commonly used in the art, for example, water or six Agents, solubilizers and emulsifiers, such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzoic acid, propylene glycol, 13-butane, alcohols, oils (especially cottonseed oil) , peanut oil, corn oil, germ oil, eucalyptus oil, sesame oil and sesame oil), glycerin, tetrahydrofurfuryl alcohol (caffeol), fatty acid esters of polyethylene glycols and sorbitol, and mixtures thereof. The oral composition may contain, in addition to the inert diluent, an adjuvant, an emulsifier and a suspending agent, a sweetener, a flavoring agent, a coloring agent, a perfuming agent, and a preservative. The suspension, in addition to HPP, also contains a suspending agent, for example, eth〇Xylated lsostearyl alc〇h〇ls, polyoxyethylene sorbitol and sorbitol, microcrystalline cellulose, Oxygen (hydrogen) chemical fertilizer, bentonite, agar and tragacanth, and mixtures thereof. The formulation for rectal or vaginal administration may be a suppository which may be prepared by admixing one or more of the HPP with one or more suitable non-skin irritating excipients or carriers. For example, cocoa butter, polyethylene glycol, suppository mash or salicylic acid, which is solid at room temperature but liquid at body temperature, thus melts and releases the sputum active agent in the rectum or vagina (10). Formulations suitable for vaginal administration also include pessaries, tampon tampons, emulsions, gels, pastes, foams or sprays, 114 201143772, which are suitable for containing such carriers well known in the art . Formulations comprising a topical, transdermal, epidermal or dermal administration of a PP, a substance, a solution, a spray, an ointment, a paste, a milk (2), and a pharmaceutically acceptable carrier may be mixed; : Required: Any preservative, buffer or propellant (P-ellants). The ointment, Γη直直剂 and gel may contain excipients in addition to the HPP composition:

The class '«贞m powder, western yellow gum, fiber, 'yy, material, polyethylene glycol, linalosteroid, bentonite, aspartic acid, slippery and zinc oxide' or a mixture thereof. Powders and sprays may contain excipients such as lactose, talc, linalic acid, hydrazine hydroxide, hydrazine: 'b and polyamide powder, or mixtures of these, in addition to the HPP combination. Sprays may additionally contain > 〇 propulsion training, such as fluorocarbons and volatile unsubstituted hydrocarbons such as Dingyuan and C. The most preferred topical or transdermal formulations are pure water, solution 3 water bath, ethanol and aqueous solutions, and isopropanol and aqueous solutions. The most preferred preparations for topical or transdermal administration are pure water, solutions, aqueous solutions, ethanol and aqueous solutions, and isopropanol and aqueous solutions. ^ HPP or a pharmaceutical composition thereof can be optionally administered as an aerosol. This can be achieved by preparing an aqueous aerosol, liposome formulation or solid particles containing the HPP. Non-aqueous (e.g., 'fluorocarbon propellant) suspensions can also be used. Super-service can also be used. Aqueous aerosols are obtainable by co-formulation of the water = solution or suspension of the agent with conventional pharmaceutically acceptable carriers and stabilizers. The carrier and stabilizer vary depending on the needs of the particular compound but may include nonionic surfactants (Tween, Puni " IS i 115 201143772 Pluronics or polyethylene glycol", harmless proteins Such as serum globulin, sorbitol esters, oleic acid, lecithin, amino acids such as glycine, buffers, salts, sugars or sugar alcohols. Aerosols can usually be prepared by isotonic solutions. Transdermal patches can also be used to deliver HPP. The composition is prepared to the target. Such a preparation can be prepared by dissolving or dispersing the agent in a suitable medium. The absorption enhancer can also be used to increase the flow of the drug across the skin. The rate of such flow can be controlled by providing a rate controlling membrane. It is also possible to control the drug in a polymer matrix or gel by moon. Ophthalmic formulations, ophthalmic ointments, powders, solutions, and the like are also intended to be included in the scope of the present invention. Formulations for parenteral administration include Hpp and one or more sterile, isotonic or nonaqueous solutions, dispersions, suspensions, or rituals of Huagan. Reconstituted into a sterile injectable solution or sub-microbial powder before use. It may contain an antioxidant, a buffer, a bacteriostatic agent, an isotonic solution to keep the blood of the medicated injection, or a suspending agent or thickener. The aqueous and non-aqueous t-types which can be used in parenteral formulations include 'water, ethanol, polyols (eg, glycerol, propylene glycol, eucalyptus oils), and suitable mixtures thereof, such as vegetable oils. Olives, Erguang main injection with organic esters such as ethyl oleate. Can maintain proper flow 1 D, by using coating materials such as printing to maintain the required _, and by using = two over the dispersant The preparation for parenteral administration may further contain an adjuvant/humidifying agent, an emulsifier and a dispersing agent, and the anti-microbial action is added to the effect of the antibacterial and antifungal substances. And antifungal agents, for example, Niper rr τ 116 201143772 ^, gas butanol, benzene # sorbic acid, and the like. Also useful in combination: containing isotonic substances such as sugars, sodium gasification, and Similar to the substance by delaying absorption, such as monostearic acid And gelatin to prolong the absorption of pharmaceutical preparations for injection. Injectable preparations can be obtained by forming HPP: or in biodegradable polymers such as polylactic acid and polyacetate. The control of the release rate of the music may depend on the gift, and the nature of a particular polymer used. Examples of other biodegradable poly-substitutes include 'poly (original acid vinegar) and poly (acid needle preparation) The preparation may also be carried out by encapsulating HPP in a monthly = micro-tie with body tissue compatible. In certain embodiments, a therapeutically effective amount of anti-H antibacterial agent-related compound Hpp' or a pharmaceutical composition thereof It can be delivered to a disease or tumor site. It is well known in the field of pharmacology that the precise amount of Hpp can produce the most effective results in the treatment of a particular patient, depending on the number of cases listed here. For example, the activity of the body chat, the specific nature, the metabolic properties of the drug, the pharmacokinetics, the availability of the substance, the physiological symptoms of the administered organism (including race, age, sex, weight, diet, disease type and stage) , overall physical symptoms, reactivity to a variety of therapeutic treatments, the pharmaceutically acceptable carrier of the preparation, the route and frequency of the treatment, the severity or tendency of the disease caused by the target pathogenic microorganism. However, the above guidelines can be used as a basis for careful regulation of treatment. In order to determine the optimal dose for administration, it is necessary to carry out routine experiments consisting of measuring the administered organism and adjusting the dose. Inflammable test

Remington: The Sconce and Pracdce of Pharmacy (cLnaro [S] 117 201143772 ed. 20.sup.th edition, Williams & Wilkins PA' USA) (2000) 〇IV·Excellent antibacterial agents (such as antibiotics) and antibiotic-related compounds It is generally hydrophilic and therefore difficult to penetrate the skin membrane barrier. When antibacterial and antibacterial-related compounds are administered orally, they may be inactivated by First Pass metabolism. In the case of injection, administration of the antibacterial agent causes pain, and it is expensive to require frequent administration and consultation. In certain embodiments, since the HPP or HPC of the present invention is permeable to one or more layers of biological barrier, the Hpp or Hpc can be administered by topical administration (eg, topical or transdermal) without systemic administration (eg, oral or injection). In the case of administration, the site where the symptoms occur is reached. Topical administration and permeation of Hpp or Hpc allows HPP or HPC to achieve a local concentration of the agent (the level of the agen(4) at the same level as the local concentration of the system when the parent drug or drug is administered, = the amount or dose of HPP or HPC Far less than the amount of parent drug or drug administered systemically; in addition, systemic administration may not achieve higher local concentrations, or, if possible, systemic administration will require very high doses of the agent. HPP or HPC or The high local concentration of the parent drug after lysis makes it more effective in the treatment of a certain symptom, or more rapid than the systemic administration of the parent drug, and makes possible previous or unknown treatment possible. It can reduce the potential pain caused by systemic administration of the organism, such as side effects of the disc agent system exposure (4), gastrointestinal reactions or renal reactions. In addition, topical administration can pass HPP or HPC through a variety of biological barriers. For example, 'total circling, reaching the system' therefore does not require systemic administration (eg, and avoids pain associated with administration of the injection. [S] 118 201143772 In certain embodiments 'HPP in the present invention or HPC or pharmaceutical compositions can be administered by sedative (eg, orally or by injection). Hpp or Hpc or HPP or HPC active agents (such as drugs or metabolites) can enter the total loop faster than the parent drug' And reach the site of action of a certain symptom. In addition, Hpp or HPC can pass through the biological barrier (such as the blood-brain barrier, blood-broth barrier), and if only the mother music can not penetrate the biological barrier, Hpp or HPC can be Impossible or unknown treatments provide new treatments. For example, the high osmotic compositions of the antibacterial or antibacterial related compounds of the present invention (HPPs/HPCs) exhibit high permeation rates to the biological barrier (eg, The antibacterial agent or the antibacterial agent-related compound is at least about 10 times, about 50 times, about 100 times, about 200 times, about 3 times, about 1 time higher than when administered alone. No side effects were observed or observed in the organisms of PP or ΗPC, while side effects (such as chewing hearts) were observed in organisms using the antibacterial agent at the same dose. With the extensive use of antibacterial agents, due to pathogens Variation over time Drug resistance has become a common and serious problem. The antibacterial or antibacterial agent claimed by the present invention is aimed at high-permeability compositions of compounds (talking feet.) = high speed penetration of biological barriers such as biofilms, bacteria, mulch And other microbial cell walls to overcome the problem of drug resistance. Υ _ implementation of the 实施 2 embodiment is intended to better illustrate the invention of the protection, and should not be construed as limiting the invention in any way. Or, the specific combination of meat, - the knives are included in the scope of the present invention. The materials and methods should not limit the invention, but only (4) specific embodiments within the scope of the invention. 119 119 201143772 Creative work and without leaving the invention 2: Under the premise of the scope of the invention, materials and methods of the calculation group can be developed. It should be understood that various changes can be made using the present invention and are still included within the scope of the invention. Variations that are 'rejected' are included within the scope of the invention. - Example 1, Method for preparing HPP from parent drug The mother of the structure of the following structural formula F-C has a drug in some embodiments:

OH

Structural F - C

HPP that can be converted to a structure with the following structural formula L_1

F

Structural Formula L-1 includes stereoisomers and pharmaceutically acceptable salts thereof, of which:

The definitions of F T , L1 , L2 , and L4 are as described above; the transport unit of the antimony antibacterial or antibacterial agent-related compound. For example, T can be selected from the collection of the aforementioned compositions. In certain embodiments of the invention, the HPP having the structural formula L-1 may be obtained by a parent drug or a derivative of the parent drug having the following formula D (for example, a helium gas or a mixed anhydride of the parent drug compound): 201143772

F

Wc

Structural Formula D and Structural Formula E (Compounds in Scheme :: t-l2-h

Structural formula E

Prepared by organic synthesis. Wherein Wc is selected from the group consisting of hydrazine H, halooxycarbonyl and substituted aryloxycarbonyloxy; ', 蛵 F Li, L2, L4 and T are as defined above. T-L2-H +

Knife Series 1. Preparation of HPP from the parent drug (I) In certain embodiments, Hpp having the structural formula L_ is prepared as in general case 1, wherein "is (4). Lower φ In certain embodiments, has the following structural formula F Master drug:

The structural formula F-N reacts with a compound having the following structural formula G: w'〆

Structural Formula G yields an HPP having the structural formula L:

121 201143772 Structural Formula L-1 wherein: includes stereoisomers and pharmaceutically acceptable salts F, L1, L2, L4, and TN are as defined above;

The transport unit of TT is an antibacterial agent or an antibacterial agent-related compound may be selected from the group consisting of w#〇R6 as described above; Μ optionally a collection of sodium, potassium I or other metals, optionally free of OH, halogen, The furnace has its π * said Wn base composition set (Scheme 2). Earth & base army

Scheme 2·Preparation of HPP from the parent drug (II) In certain cross-linking modes, Hpp having the structural formula L_i can be prepared by organic synthesis 'reactive reaction elements which can be unneeded before being connected to the transport unit and the functional unit Points such as -C(=0)〇H, _Nh2, _〇H, or _SH are protected. In some embodiments, the obtained protection Hpp can be further developed

Deprotected either partially or completely to obtain a protected Hpp or unprotected HPP, respectively. Preparation of 6-phenoxyacetamidine penicillin acid 2·diethylaminoethyl ester hydrochloride 39 g of penicillin V potassium salt was dissolved in i〇0m丨acetonitrile. An ethyl acetate mixture of 39 g of 2-bromo-indole, hydrazine-diethylethylamine hydrobromide was added to the reaction mixture. The mixture was stirred at room temperature for 16 hours. 39 g (0.15 mol) of 2-bromo-N,N-diethylethylamine hydrogenate and 3Og of sodium hydrogencarbonate were added to the reaction mixture. The mixture was stirred at room temperature for 12 hours. The solid was removed by filtration. 3.5 g of HCI dissolved in 50 π τ ^ 122 201143772 was added to the reaction mixture with stirring. Over the collection of solid products. After drying, 38 g of a hygroscopic product was obtained in a yield of 78.2%. Elemental analysis: C22H32C1N3〇5S; molecular weight: 486 〇. Calculated. /〇C : 54.37 ' Η : 6.64, N : 8.65 ' C1 : 7.29, 〇: 16.46, S : 6.60 ' Measured value % c: 54.32 ' Η : 6.68, Ν : 8.61, C1 : 7,32, 〇: 16.51 , S: 6.56. Preparation of ό_(2,6·dimethoxybenzamide) penicillin acid_2_diethylaminoethyl ester 10 salt 38 g of 6-(2,6-dimethoxybenzamide Penicillin acid was dissolved in 300 ml of gas. To the reaction mixture were added 2 〇 6 g of N N, dicyclohexylcarbodiimide, 11.7 g of N,N-didecylaminoethanol, and 2 g of 4·didecylamino ratio σ疋. The reaction was stirred at room temperature for 1 hour. Over the solids. The gas imitation layer was washed twice with 5% sodium hydrogen carbonate solution (2 x 100 ml) and then washed 3 times with water (3 Χ 1 〇〇 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. 3 · 5 g of vaporized hydrogen dissolved in ^ φ ethyl bond was added to the reaction mixture under stirring, and the solid was collected by filtration to produce ασ. After drying, 40 g of hygroscopic product was obtained with a yield of 77.5 %. Elemental analysis: C23H34C1N306S; molecular weight: 516.05. Calculated value % c : 53 53 , Η : 6.64, N : 8.14, C1 : 6.87, Ο : 18.60, S : 6 21, measured value % C : 53.49, Η : 6.68, Ν : 8.1 卜 C1: 6.9 〇, 〇 : 18 64 , S : 6.18. Preparation of ethyl phenyl phenyl phenyl phthalate 2 - diethylamino propyl hydride hydrochloride [S] 123 201143772 Take 43g of B. In 100 ml of acetonitrile. A mixture of 40 g of 2-bromo-N,N-diethylpropylamine hydrobromide in ethyl acetate was added to the reaction mixture. The mixture was stirred at room temperature for 16 hours. 40 g of 2-bromo-N,N-diethylpropylamine hydrobromide and 3 g of sodium hydrogencarbonate were added to the reaction mixture. The mixture was stirred at room temperature for 12 hours. Remove the solids. 3.5 g of HCl dissolved in 50 ml of diethyl ether was added to the reaction mixture with stirring. The solid product was collected by filtration. After drying, 35 g of hygroscopic product was obtained. Elemental analysis. C26H33CIN4O5S; molecular weight: 541.11. Calculate 0 value % C : 55.49 ' Η : 6.89, N : 10.35, C1 : 6.55,0 : 14.78, S : 5.92 'Measured value % C : 55.44 ' Η : 6.92, Ν : 10.32, C1 : 6.58,0 : 14.82 , S: 5.92. Preparation of 6-(5-mercapto-3-phenyl-2.isoxazoline·4-mercaptoamine) penicillin acid 4_foxidine ethyl ester hydrochloride 50g 6-(5-mercapto-3- Sodium phenyl-2-isoxazoline _4_nonylamino) penicillin sodium was dissolved in 100 ml of acetonitrile. An ethyl acetate mixture of 38 g of 4-acridine ethylbromohydrobromide was added to the reaction mixture. The mixture was stirred at room temperature for 16 hours. 38 g of 4-acridine ethylbromohydrobromide and 3 g of sodium hydrogencarbonate were added to the reaction mixture. The mixture was stirred at room temperature for 12 hours. The solid is removed by filtration. 3.5 g of HCl dissolved in 50 ml of diethyl ether was added to the reaction mixture with stirring. The solid product was collected by filtration. After drying, 3 〇g of hygroscopic product was obtained. Elemental analysis: C26H33ClN4〇5S; molecular weight: 549.08. Calculated value % C : 56.88 ' Η : 6'06, N : 10.20, C1 : 6.46, Ο : 14.57, S : 5.83 ' Measured value %C : 56.85, Η: 6.08, Ν: 10.19, C1: 6.47, rr L ο 124 201143772 Ο : 14.59,S : 5.82. 3-[[(aminocarbonyl)oxy]methyl]-7-methoxy-8-oxo-7-indole (2-thienylethyl hydrazide)amino)]·5·thia-1-azabicyclo _[4.2.0Buxin-2·ene-2-carboxylic acid 2-diethylaminoethyl ester hydrochloride preparation 41 g of 3-[[(aminocarbonyl)oxy]methyl]_7_decyloxy_8 _Oxo-7-[(2-nonylphenyl)amino)]_5_thia-1-azabicyclo-[42〇] sodium octa-2-ene-2-carboxylate dissolved in "( ^ 丨 acetonitrile. A mixture of 35 g 2 ^ ^ _ N, N _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ N,N_:ethylethylamine hydrogen/o-acid salt and 30 g of sodium hydrogencarbonate were added to the reaction mixture. The mixture was stirred at room temperature for 12 hours, and the solid was removed by filtration. 3 5 g dissolved in 5 〇m 丨 ether. HC1 was added to the mixed solution under stirring. The solid product was collected by filtration. After drying, 30 g of a hygroscopic product was obtained. Elemental analysis: C22H31C1N407S2; molecular weight: 563.08. Calculated value % c ·· 46.93, boxing. 5_55, N: 9.95, C1: 6.30' 〇: 19.89, S: 11.39, measured value % C : 46.91, Η : 5.57, N : 9.93 , C1 : 6.32, 0 : 19.91, S : 11.36. The antimony of other antibacterial or antibacterial-related compounds can also be synthesized by a similar method. Example 2 'Antibacterial or antibacterial agent-related compound ΗΡΡ shows compared with its parent drug The higher in vitro permeation rate of the human skin and the permeability of the parent drug to the human skin are measured by the in vitro improved 125 201143772 vertical test diffusion penetrator (Franz cells). The vertical test diffusion/permeability device (Franz cells) has two The chamber, the upper sample chamber and the bottom chamber, separate the human skin tissue (thickness 36 〇 _4 〇〇 μηι) from the top and the receiving chamber, and are separated from the front and rear regions of the thigh. The detected compound [2 ml, concentration 10%, 〇·2 Μ 酸盐 buffer solution pH 7.4] was added to the sample mouth of the vertical test diffusion permeameter (Franz cens). The junction chamber contained 10 ml of phosphate with pH 7.4. Buffer solution (0.2 M). The solution was stirred at 600 rpm. The amount of penetration of the compound into the skin was measured by high performance liquid chromatography-HPLC (HPLC). The results are shown in Figure iai, Figure 1 a2, Figure 1 a3, Figure 1 A4, Fig. 1b and Fig. 1c, the apparent flux values of the test compounds were calculated according to the slopes of Fig. 1a, Fig. la2, Fig. la3 and Fig. U4, and are summarized in Table 1a. According to Fig. 1b, the apparent Tongli values calculated from the slope of Fig. 1c are summarized in Table 1b and Table 1c, respectively. Since the minimum detection limit of the apparent flux value in this method is i

Pg/cm2/h, a parent drug with an apparent flux value equal to or less than 1 pg/cm2/h is considered to be undetectable infiltration of skin tissue. For parent drugs with small apparent flux values (eg penicillin V, penicillin 0), HPP has a detectable apparent flux value. For apparent flux values greater than! The parent drug of pg/cm2/h has a higher apparent flux value for their HPP. Therefore, the HPP of the antibacterial or antibacterial-related compound exhibits a higher penetration of skin tissue (340-600 times) than the parent drug. 〆平表 la. Permeation rate of HPPs and their parent drugs in vitro (ι [S1 126 201143772 HPP structure # HPPs HPP apparent flux value (mg / cm2 / h) The apparent flux of the parent drug ( Mg /cm2/h) P-83 6-phenoxyethylaminocyanine 0.72±0.06 Penicillium &lt;0.001 mycinic acid 2-diethylaminoglycolate V-ethyl ester hydrochloride P-84 allylthiol Penicillium 0.65 Penicillium &lt;0.001 acid 2-diindoleaminoethyl ± 0.05 thiol ester hydrochloride P-11 6-(2,6-dimethoxybenzene 0.52±0.07 methoxy &lt;0.001 carbamide) penicillin Acid 2- phenylqingdipropylaminoethyl ester salicylate P-2 6-(5-mercapto-3-phenyl-2-0.77±0.08 benzoic < 0.001 isoxazoline-4-indole Indoleamine, apoxia, penicillin, 4-acridine, sodium, ethyl acetate, hydrochloride, P-2, 6-[3-(o-phenyl)-5-0.85±0.05, adjacent gas &lt;0.001 thiol- 4-isoxazole Penicillium Amino] Penicillin 3-Aziridine Ethyl Acetate [s] 127 201143772 P-2 6-[3-(2,6-Diphenyl)-5-曱4-isoxazole guanamine amino] penicillin acid 1-acridine ethyl ester hydrochloride 0.58 ± 0.05 dichloro blue [&lt;0.001 P-3 6 - [ D (-) - a - gas - phenylethylamino) penicillin ethyl ester hydrochloride 0.82 ± 0.06 ampicillin &lt; 0.015 P-7 D - α - [(σ米嗤烧-2 -酉-1-yl)carbonylamino]benzylpenicillin 2 -tetrahydro α specific methyl ester hydrochloride 0.72±0.05 azlocillin &lt;0.001 P-85 6R-[2 -[3-(oxasulfonyl)-2-oxo-1-imidazolidineamino]-2-phenylethylamino]penicillin acid 1-tetrahydropyrroleethyl ester hydrochloride 0.79±0.07 Xilin&lt;0.001 P-1 6-D(-)-a-(4-ethyl-2,3-dioxo-1-° melon. Qinmethyl guanidine amino)-α-phenethyl hydrazine amino penicillin- 2-Diethylaminoethyl ester hydrochloride 0.74 ± 0.08 σ guaracillin &lt; 0.001 P-19 7-(2-thienyl oxime amino) 0.62 ± 〇. 〇 6 cephalosporin &lt; 0.001 128 201143772

_ cephalosporin-2-diethylaminoethyl ester hydrochloride p-86 7-[(hydroxyphenylethyl)amino]-3-[[(l-methyl-1H-tetrazole-5 -yl)thio]indolyl]-8-oxo-5-thia-1-rhamidobicyclo[4.2.0]oct-2-py-2-nonanoic acid 2-diethylaminoethyl ester hydrochloride 0.75±0_05 Cefmendoxime &lt;0.001 P-26 3-[[(aminocarbonyl)oxy]indolyl]-7-[[2-furyl(methoxyimino)ethinylamino]-8-oxygen -5-5-thia-1-azabicyclo[4.2.0] octa-2-fine-2-indoleic acid 2-diethylaminoethyl ester hydrochloride 0.67 ±0.04 cefuroxime &lt;0.001 P-14 3-[[(aminocarbonyl)oxy]indolyl]-7-decyloxy-8-oxo-7-[(2-thienylacetyl) gas group)]_5_thia-1-azabicyclo -[4.2.0]-octyl-2-fine-2 -nonanoic acid 2-diethyl 0.61±0.05 cefoxitin &lt;0.001

129 201143772 Aminoethyl ester hydrochloride P-62 7-[[[2-(Ethylaminomethyl)phenyl]ethinyl]amino]-3-[[[1-(ethoxycarbonylcarbonyl)] -1Η-tetrazol-5-yl]thio]indolyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-rebel 2-diethyl Base gas ethyl ester hydrochloride 0.52 ± 0.04 ceftriax &lt; 0.001 P-20 7-[(ethylaminophenyl ethinyl) amino]-3-chloro-8-milo-5-thia- 1-Azabicyclo[4.2.0]oct-2-ene-2-sodium 2-ethylglycolate hydrochloride 0.71±0.05 cefaclor &lt;0.016 P-29 3-[( Oxy)indolyl]-7-[[(2-acetamido-4-thiazolyl)(nonoxyimino)ethinyl]amino]-8-oxo-5-thia-1-rat Heterobicyclo[4.2.0]oct-2-pyridin-2-decanoic acid 2-diethyl0.73±0.06 cefotaxime&lt;0.018

130 201143772 Aminoethyl ester hydrochloride P-28 7-[[(2-Ethylamino-4-0.62 ± 0.05 cephalosporin &lt;0.010 thiazolyl) (oximeimino)ethylamino]amino]-8-oxygen -5-5-thia-1 -rhamidobicyclo[4.2.0]oct-2-ene-2-decanoic acid 2-diethylcarbylethyl ester hydrochloride a stagnation P-39 7-[[ [[(4-ethyl-2,3-two 0.57±0.04 cephalosporin &lt;0.015 oxo-1 - σ guanidine) carbonyl] amino](4-ethyl phenyl) ethinyl]amino]-3- [[(1-indolyl-1Η-tetrazol-5-yl)thio]indolyl]-8-oxo-5-thia-1-azabicyclo[4.2.0] 辛-2-kun- 2-Resin 2 -diethylaminoethyl ester hydrochloride 17 melon ketone P-46 7-[2-(2-Ethylene-based 4-0.51±0.03 cephalosporin &lt;0.001 thiazolyl)-2-( (Ζ)-曱 肟 肟 肟 imino)acetic acid amino]-3-(decyloxy oxime ester [s] 131 201143772 base)-8 -oxo-5-thia-1-azabicyclo[4.2.0 ] oct-2-ene-2-carboxylic acid 2-diethylaminoethyl ester hydrochloride P-45 7-[2-(2-acetamido-4-thiazole)-2-((Z)-B Oxycarbonylcarbonyloxy)imino]ethinylamino]-3-(vinyl)-8-oxo-5-thia-1-heterobicyclo[4.2.0]oct-2_fried-2 -竣2-diethylaminoethyl ester hydrochloride 0.58±0.05 Cefixime&lt;0.010 Table lb. p-endoprostanase inhibitor HPPs and their parent drug penetration rate in vitro (II) HPP structure # HPPs HPP Apparent flux value (mg /cm2/h) Apparent flux value of parent drug (mg /cm2/h) 1-4 [28-(2α,3β,5 〇0]-3-methyl 0·32±0.0 3 [2S-(2a,30,5 〇〇]-3-曱基&lt;0.001 [S] 132 201143772

-7-oxo-3-(1Η-1,2,3-azido-1-ylmethyl)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid 4 , 4-dimer 1 - π guadidine ethyl ester hydrochloride (tazobactam-PEE) • 7-oxo-3-(1Η-1,2,3 - abundance _ 1 -ylmethyl -4 -thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid 4,4-dioxygen salt (He. sittan) 1-3 (2S, 0.35 (2S, &lt;;0.001 5R)-3,3-di±0.03 5R)-3,3-dimethyl-7-oxomethyl-7-oxo-4-thia-1 -4-thia-1 Azabicycloazabicyclo[3.2.0]heptane[3.2.0]heptane-2-carboxylic acid-4,-2-carboxylic acid-4,4-dioxide 4-naphthalene, Ν- Diethyl (sulbactam) aminoethyl ester hydrochloride (Suba

133 201143772 Ketan-DEE), 1-2 (2R,5R,Z)-3 0.29 ±0·0 (2R,5R,Z)-3 &lt;0.001 -(2- via ethylene 2 -(2- via ethylene (7-oxo)-7-oxo-4-oxa-1- -4-oxa-1-azabicycloazabicyclo[3.2.0]-heptane [3.2.0 ]-heptane-2-carboxylic acid 4-indole-2-carboxylic acid (ketoethyl ester hydrochloride lavic acid) salt (clavulanic acid-PEE) 1-9 [(N-oxime oxycarbonyl 0.37 ± 0.0 [( N-oxime carbonyl < 0.001 amino group) methyl 3-amino) methyl]-phosphonic acid]-phosphonic acid mono-(4-nitrophenyl-(4-nitrophenyl)(Ν,Ν-二(S) is a salt of ethylaminomethyl) ester. Hydrochloride 1-33 [(Ν-卞 oxycarbonyl 0.25 ± 0.0 [(N-oxime carbonyl &lt; ]-phosphonate]-phosphonic acid mono-(3-0-sigma-based)-(3-anthracene sigma)

134 201143772 ci-acridine ethyl ester. Hydrazine hydrochloride sodium salt table lc. sulfonamides, hydrazine and quinolones HPPs and their parent drug penetration rate in vitro HPP structure # HPPs 表 apparent flux value ( Mg /cm2/h) Apparent flux value of parent drug (mg /cm2/h) S-1 4-(4-dimethylamino 0.18±0.03 4-aminobenzene &lt;0.001 butylbutyrate) Amino stone yellow amine benzene sulfonamide. Hydrochloric acid (p-amino salt (DMAB-p-aminobenzenesulfonyl benzene sulfonamide) amine) S-9 6-oxo 0.21 6-oxo &lt;0.001 -3-( 2-[4-(7V-a ratio ±0.03 -3-(2-[4-(0)-2-based gas continued to brew TV-0 than bit-2-yl)phenyl]-linked or continued Amino)cyclohexyl-1,4-yl)phenyl]diene carboxylic acid hydrazine, hydrazine-methyleneaminoethylaminopropyl)cyclohexane 135 201143772 ester. hydrochloride (sulfasalazine-DEPE) - ------1,4-dienic acid (sulphonium sulfonamide) T-15 1-cyclopropyl-6-fluoro 0.29±0.02 1-cyclopropyl &lt;0.001 -4-oxo -7-azine 6-fluoro-4-yl-yl-salin-3-deoxy-7-decanoate. hydrochloride salt-1-yl-(ciprofloxacin-BE) quinoline -3 -carboxylic acid (ciprofloxacin) S-11 1-ethyl-7-mercaptopurine.25±0.〇4 1-ethyl-7- &lt;0.001 -4-oxo-[1,8] Naphthylmethyl-4-oxopyridine-3-carboxylic acid N,N-substituted-indole,8] diethylaminoethylnaphthyridin-3-carboxylate hydrochloride (naphthyridic acid (naphthalene, acid-DEE) -----Citrate) Example 3 The rate at which HPPs penetrate the skin and/or blood-barrier barrier in vivo The rate of skin and blood-brain barrier of invasive nude mice infected with HPPs in vivo was investigated. The donor consisted of 1 ml of a solution of 20% dissolved in isopropanol selected from the group consisting of 6-(2,6-dimethoxybenzamide) penicillin-ethylaminoethyl ester hydrochloride, 6 -(5-methyl-3-phenyl-2-isoxazoline _ sulphate) phleic acid-2-diethylaminoethyl ester hydrochloride, 6_[3_(o-gas :^ 136 201143772 ))-5-Methyl-4-isoxamethylene carbamide] penicillin acid _2_diethylaminoacetate hydrochloride, methicillin, oxacillin and oxacillin. They were applied to the 10 cm2 portion of the back of the hairless mouse. After 2 hours, the mice were killed. The lg blood, lg liver, lg kidney, lg muscle, or lg brain, which had been uniformly processed, were added with 5 ml of sterol, centrifuged for 5 minutes, and then determined by HPLC (Table 2). Only the nude mice given the parent drug (methicillin, oxacillin and azoxycillin) did not detect the corresponding drug. The results show that the prodrug penetrates the blood-brain barrier well and the corresponding parent drug does not penetrate the skin. Permeation results of HPPs of intrinsic antibiotics in ships HPP (6-(2,6-dimethoxybenzamide) penicillin 2-ethylaminoethyl ester hydrochloride 6-(5-曱3-phenylisoindolyl-4-meramine) penicillin 2-ethylaminoethyl ester hydrochloride 6_[3-(o-phenylphenyl)-5-methyl_4_曱 曱 曱 ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ]詈 blood (^g/g) 27+/-6 28+/-5 25 +/.S Liver (Pg/g) 15+/-5 18+/-7 ^------ 14+/ -6 Kidney 15+/-5 16+/-5 12 +/_7 ----- Γ Γ- 1 L -J i 137 201143772 bg/g) Muscle (gg/g) 20 +/-5 22 +/ -5 20 +/-7 brain (pg/g) 11 +/- (5 8 +/-6 9 +/-5 Use 90 milk-producing cows. Dissolve in the breast in 10ml phosphate buffer solution at pH 7.4 6-phenoxyethyl hydrazine amino-monic acid 2-diethylaminoethane g-hydrochloride (penicillin v_dee), 6-(2,6-dimethoxybenzamide) penicillin 2_ Diethylaminoethyl ester hydrochloride (methicillin _DEE) or 7_[[(2_醯Amino_4_thiazolyl-milk-milk-based ethylamino]-oxo-oxo-5-thiazepine-azabicyclooctyl-2-butan-2-acid ethyl 2-diethylaminoacetate hydrochloride (Cefmenoxime-dee). After taking the prodrug for external use, take the milk sample analysis (Table 3). The knot can not be detected, this is also the right phase of the front ^ I (1) Le is very embarrassing The blood-milk barrier penetration rate ^, the blood W-brain barrier permeability makes these drugs highly valuable in the fine, thoracic 'prostate and other infections.

Penicillin V Methicillin---_____ The amount of parent drug measured in breast milk after external use----- pg/g 138 201143772 -DEE Cephalosporin-DEE Ceftizoxime 28 +/-6 pg/g Example 4 'jjpp of antibacterial or antibacterial-related compound showed higher bacterial cell wall permeation rate than its parent drug. 0.5 mmol of test compound (6-phenoxyethyl hydrazine aminopenicillin acid acridine ethyl ester hydrochloride Salt (penicillin V-PEE), penicillin V, 6_(2,6-dimethoxybenzene f decylamine) penicillin acid 2-tetrahydropyrrole methyl ester hydrochloride (methicillin _ -PME), methicillin ,7-[[(2-Ethylamino-4-thiazolyl)(methoxyimino)ethyl]yl]-8-oxo-5-thia-1-azabicyclo[4.2.〇 ] 辛_2_ ene-2 - oxo acid 2-ethylaminoethyl ethane hydrochloride (cephem sdee) or ceftizoxime was added to 100 ml of E. coli suspension and stirred for 3 minutes. Methods Escherichia coli was collected and washed three times with phosphate buffer of pH 7.4. Finally, 100 ml of acetonitrile was added to the E. coli pellet, and the suspension was heated at 60 °C for 2 minutes. The acetonitrile solution was collected, then The amount of the drug was determined by HPLC method. The results are shown in Table 4. Table 4: The amount of the drug into the Escherichia coli cells The acesulfame V V-DEE The methicillin methicillin-DPE head Run U sputum cephalosporin ° sitting -DEE cells in the drug 0.2 55 0.25 50 —--- 0.2 53 139 201143772 amount (mmol / gram wet cells)) Example 5, HPPs can be converted into its parent drug anti-spasm HPPs of agents or antibiotic-related compounds can be rapidly converted into antibacterial or antibacterial-related compounds as a parent drug in human plasma. The Hpp of 1 Omg of the antibacterial or antibacterial agent-related compound was dissolved in a phosphate buffer solution (〇 2M ) of 〇 1 w Φ pH 7.4. 1 ml of human plasma was preheated to 37 ° C and added to the solution, and the mixture was placed in a 37 π water bath. In the name of every 2, 0.2 ml of the mixture was taken out, and then 4 ml of methanol was added to the plasma protein. After centrifugation for 5 minutes, it was analyzed by high performance liquid chromatography. The results showed that most of the antibacterial or antibacterial-related compounds of 11卯5 could be converted into antibacterial agents or antibacterial-related compounds (Table 5). Table 5. The half-life of HPP in plasma HPP half-life of the parent drug (min) 8 +/- 1 6-phenoxyethyl amino-glycine 2-diethylaminoethyl ester hydrochloride penicillin V allyl sulfur Methyl penicillin-2-diethylaminoacetic acid hydrochloride Phytosin 0 8 +/- 1 6-(2,6-dioxabenzamide) Penicillin _2· 曱 西 10 +/-1 140 201143772 Diethylaminoethyl ester hydrochloride 6-(5-fluorenyl-3-peptidyl-2-isoxan*&gt;salt-4-mercaptoamine) penicillin acid diethyl Aminoethyl gluconate hydrochloride stupin sylvestre 12 +/- 1 6-[3-(o-o-glycol)-5-mercapto-4-isoxan alpha sylvestylamine penicillin-2- Diethylaminoethyl ester hydrochloride gas °Sylylene 8+/-1 6-[3-(2,6-diazabenyl)-5-mercapto-4-isoxanthine-ylamino] Penicillin-2-diethylaminoethyl ester hydrochloride Diclocillin 12+/-1 6-[D(-)-a-acetic acid aminophenylethylamino] chlorophytate-2-di Aminoethyl ester hydrochloride Ampicillin 10 +/- 1 Da-[(imidazol-2 keto-1-yl)carbonylamino] chlorhexidine-2 -diethylaminoethane Azlocillin 9+/-1 6R-[2-[3-(methyl sulphate)-2 - oxygen代-1-口米嗤院曱醯Amino]-2-phenylethylamino]penicillin-2-diethylaminoethyl ester hydrochloride mezlocillin 13+/-1 6-D(-)-a -(4-ethyl-2,3-dioxo-l-σ lysylamino)-α-phenethylaminocyaninic acid_2-diethylaminoethyl ester hydrochloride foxcillin 15+ /-1 7-(2-Thienyl oxime amino) cephalosporanic acid 2-diethylaminoethyl ester hydrochloride cephalosporin 9 +/- 1 7-[(hydroxyphenylethyl)amino]_3- [[(1_methyl_ih_ cephemen 10+/-1 141 201143772

Tetrakis-5-yl)thio]indolyl]azabicyclo[4.2.0]oct-2-ene-2-furic acid 2-diethylaminoethyl ester hydrochloride 3-[[(aminocarbonyl)U Methyl]^(methoxyimino)ethinylamino]·8_oxo_5_thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 2-diethyl Base aminoethyl ester hydrochloride Τ~---- multi-cefuroxime 8+/-1 3-[[(aminocarbonyl)oxy]methyl]-7-decyloxy_8_oxo·7·[ (2-thienylethenyl)amino)]_5_thia-1-azabicyclo-[4.2.0]oct-2-ene_2-carboxy oxime 2 - ethylethyl acetoacetate hydrochloride Cefoxitin 7 +/- 1 7_[[[2-(ethylideneaminomethyl)phenyl]ethinyl]amino]-3-[[[1-(ethoxycarbonylmethyl)) Η_tetrazole -5-yl]thio]indolyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid 2-diethylaminoacetate Cefrelide 9+/-1 7-[(Ethylaminophenylethenyl)amino]-3- gas-8-oxo-5-thia-1-azabicyclo[4.2.0] Oct-2-ene-2-carboxylic acid 2-diethylaminoethyl ester hydrochloride cefaclor 8 +/- 1 3-[(ethyloxy) fluorenyl]-7-[[ (2-B Amidino-4-thiazolyl)(methoxyimino)ethinyl]amino]_ 8-oxygen -5-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2.carboxylic acid 2-diethylaminoethyl ester hydrochloride cefotaxime +/- 10+/-1

142 201143772 7-[[(2-Ethylamino-4_thiazolyl)(曱oxyimino)ethinyl]amino]-8-oxo·5·thiazeto_ι_azabicyclo[4.2.0 ] oct-2-diethyl-2-acid 2-diethylaminoacetate hydrochloride cephalosporin.肟11+/-1 7-[[[[(4-ethyl-2,3-dioxo-1 -pyridazine)carbonyl]amino](4-ethylphenyl)ethyl)amino] -3-[[(l-fluorenyl-1H-tetrazol-5-yl)thio]indolyl]-8-oxo-5-thia-1-azabicyclo[4.2.0] octan-2 -ene-2-carboxylic acid 2-diethylaminoethyl ester hydrochloride cefotaxime 12+/-1 7-[2-(2-acetylamino-4_thiazolyl)-2-((Z) -methoxyimino)ethylamino]-3-(decyloxyhydra)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-dicarboxylic acid 2 -Diethylaminoethyl g-hydrochloride cefpodoxime 8 +/- 1 7-[2-(2-acetamido_4_thiazole)_2_((z)-ethoxycarbonylmethoxy) Imino]ethinylamino]_3_(vinyl)-8-oxo-5-thia-1-azabicyclo[4.2,0]oct-2-ene-2-carboxylic acid 2-diethylaminoethyl Ester hydrochloride Cefixime 9+/-1 Example 6. Minimum inhibitory concentration of hpps of antibacterial or antibacterial-related compounds (MlCs) according to the method disclosed in the research literature (jennifer μ. Andrews, Journal of Antimicrobial Chemotherapy 48 5 suppl. SI &gt; 5-16s] 143 201143772 (2001)) The minimum inhibitory concentration (mic) of the antibacterial agent and its prodrug was determined. The HPPs of these antibacterial agents were effective in overcoming the resistance to methicillin-resistant Staphylococcus aureus (MRS A) based on the results of minimum inhibitory concentrations (Tables 6a-6c). Table 6a. Minimum inhibitory concentration (MIC) (mg/L) of several antibacterial agents and their prodrugs against methicillin-resistant Staphylococcus aureus (MRSA). Penicillin V Penicillin V-PE E Penicillin Penicillium-PME cephalosporin σ sulcus sulphate sputum loss-DEE MIC (mg/L) 3524 1 2157 10 2786 0.5 Table 6b · Minimum antibacterial concentration MICs of various antibiotics plus p-lactamase inhibitors or their prodrugs ( Mg/L) antibiotics, large intestines, pneumonia, cray, gut, intestinal fragile, Bacillus cerevisiae, ceftriaxone 16 0.5 1 8 ceftriaxone / he 8/1 0.3/0.0375 0.3/0.03 4/0.5 σ sitting Batan 75 ceftrid Pine/He 2/0.25 0.05/0.006 0.1/0.01 1/0.125 Zoabatam-PEE 25 25 144 201143772

Table 6c. MiCs (mg/L) of Sulfonamides and Quinolones and Their Prodrugs Antibiotics Escherichia coli Staphylococcus aureus Enterococcus faecal Ester 10 64 55 DMAB-sulfamethoxazole 0.5 1 1 Cyclopropyl Sha Xing 10 128 2 Ciprofloxacin-BE 0.2 5 0.05 Naphthoquinone 6 158 64 Nalidixic acid-DEE 0.2 5 1 Ampicillin 6 0.3 5 68 Ampicillin/Ten: 3/0.375 0.1/0.0125 3/ 0.3 75 30/3.75 Batanamide/Xinyan/0.5; 0.5/0.06 0.01/0.001 0.05/0.0 5/0.625 Batan-DEE — 25 25 0625 Example 7, Antifungal or Antimicrobial Related Compounds Antifungal Activity According to Roether W. Reported method determination (R〇ether W. et al., Mykosen 27 (1) ' 14-28 (1984)) 6- oxoacetamido penicillin acid 2-diethylaminoethyl ester hydrochloride ( Penicillin v_dee), 6-(2,6-dimethoxybenzamide) penicillin 2-ethylaminoethyl ester hydrochloride (Pemonicacillin 145 201143772-DEE) or 7-[[( 2·Acetylamino|oxazolyl)(methoxyimino)ethinyl]amino]-8-oxo_5_thia-i-azabicyclo[4 2 〇]oct_2_ene_2 _carboxylic acid 2-ethylaminoethyl ester hydrochloride ( Antifungal activity of ceftizoxime_DEE). The results are shown in Table 7: Table 7. Minimum inhibitory concentration of antibacterial agent in vitro (nig/L) Pathogen penicillin V-DEE Methicillin-DEE Ceftizoxime-DEE Aspergillus nidulans 3 8 4 Hairy Bacteria 12 22 9 Sporozoites 2 8 2 Candida albicans 7 16 8 Aspergillus niger 3 9 4 Trichophyton tereus 2 12 4 Penicillium 2 9 3 Fusarium oxisporum 3 8 5 Fusarium aquaductum 2 10 3 Aspergillus 3 9 5 Example 8, HPPs of ρ·endamine antibiotics or related compounds were used for 146 201143772 Clinically treated mastitis 90 cows secreted with milk were selected. Bacteriological cure means that the sample taken from the money on the first and the 22nd day did not detect the bacteria. The clinical cure refers to the disappearance of clinical symptoms (the clinical symptoms are completely eliminated! The clinical cure after the day), in other words It is the recovery of food intake, rectal temperature &lt; 39.0 ° C, good systemic symptoms, disappearance of breast edema, normal milk properties, normal milk production. On the skin of the breast, the mouth of the breast 50 〇 111 § dissolved in 1 〇 11111) 1 ^ value of 7.4 in the tank acid salt buffer solution of 6-phenoxyethyl amino penicillin acid 2 - diethylaminoethyl ester hydrochloride ( Penicillin V_DEE), 6_(2,6-dimethoxybenzamine) penicillin acid 2_diethylaminoethyl ester hydrochloride (methicillin-DEE) or 7·[[(2-acetamidine) Amino-4 thiazolyl)(methoxyimino)ethinyl]amino]_8_ oxothia-1.azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 2-diethyl Aminoethyl ester hydrochloride (cefazodime-dee). The results are shown in Table 8a and Table 8b. The results indicate that these prodrugs can achieve good clinical cure rates and bacteriological cure rates. Table 8a: Clinical cure rate of new antibiotic prodrug for local administration of cow mastitis (22 days) Procurement rate of prodrug cows (%) Day 3 Day 8 Day 15 Day 22 Penicillin V-DEE ----- 30 50 90 93 97 147 201143772 Methotrexate-DEE 30 43 90 97 100 Ceftizoxime-DEE 30 53 93 99 100 Table 8b: Topical administration of novel antibiotic prodrugs to cow mastitis Bacteriology cure rate pathogen HPP penicillin V-DEE 曱oxypenicillin-DEE cephalosporin-DEE Staphylococcus aureus cows only 6 5 6 cure number (% cure rate) 4 (67%) 4 (80%) 5 (83%) __ S. cerevisiae cows only 10 10 11 Cure number (% cure rate) 8 (80%) 7 (70%) 9 (82%) E. coli cows only 8 10 8 Cure number (% Cure rate) ------- 7 (87.5%) ------- 8 (80%) 7 (87.5%) Cows only

148 201143772 The number of cures) 7 (78%) 6 (85.7%) 7 (87.5%) The cure rate of Enterobacteriaceae cows only 7 6 (85.7%) —i_____ 6 (75%) 6 5 (83.3 %) Example 9. Prodrug of antibacterial agent against Mycobacterium tuberculosis activity #6-year-old female mice (balb/c claw 1. 6) were infected by air-borne means 2.21 ± 〇.15乂1〇3匚? 11 Mycobacterium tuberculosis 113711¥. After 20 days, the mean CFU of the lungs was 8 23 ± 〇 27 x 1 〇 7 cfu, followed by drug treatment. Group A was a blank control group (n=2〇), and group B mice were treated with isoniazid/moxifloxacin/pyrazinamide (〇18/〇22/1 2mm〇l/kg, orally) for 45 days. Group C mice were treated with isoniazid/moxifloxacin/pyrazinamide (0·1 8/0.22/1.2 mmol/kg, orally) for 9 days, and group D mice were treated with n_(n_ φ methyl-benzene. Alanine) Isoniazid (prodrug - isoniazid, administered by N-methylphenylalanine and isoniazid to 'transdermal administration') / cyclopropyl_7_[(is,6S)- 28--Azabicyclo[4.3.0]nonane-8-yl]-6-fluoro-8-methoxy-4-oxo-quinoline_3_decanoate (prodrug-moxifloxacin) /Pyrazinic acid N,N-diethylaminoethyl (prodrug _pyrazine acid) (0.18/0.22/1.2111111〇1/1^' transdermal administration) for 45 days, the prodrug of the Qiu group mice ·Isophorin / prodrug - moxifloxacin / prodrug _ | 1 than olfactory acid (0.18 / 0.22 / 1.2mmol / kg, transdermal drug delivery) treatment for 9 days, group F mice with #药-I smoke Plough/prodrug-moxifloxacin)/prodrug-pyridoxine 2 (0.06/0.07/0.4mmol/kg, transdermal administration) for 45 days, sputum group for mice with 149 201143772 prodrug - isoniazid / former Medicine - moxifloxacin / life more l / king / then Le - bismuthazine acid (0.06/0.07/0.4mm 〇l/kg, transdermal administration) for 9 days. After the treatment was stopped, the mice continued to be cultured for 9 days (without medication), and then the treatment was performed after the death: the rate of negative lung culture was cured. The result showed that the prodrug was superior to the parent drug and the transdermal drug was effective ( Tables 9a and 9b).

Drug combination blank group (A) before treatment 45 days after treatment death after 90 days 8.23±0. 27 χ1〇7 death 3.23±0.35 103 .23 soil 0.35 isoniazid / moxifloxacin / pyrazinamide

0.18/0.22/1.2mmol/kg, orally

Isoniazid / moxifloxacin / ° ratio 11 qinamide 0.18 / 0.22 / 1.2mmol / kg, oral prodrug - isoniazid / prodrug - moxifloxacin / prodrug - 〇 σ 秦 酸 acid, 0.1 8 / 0.22/1.2mmol/kg, transdermal [S] 150 201143772 Prodrug - Isoniazid / Prodrug - Moxifloxacin / Prodrug - 0 ratio. Qin acid, 0.18/0.22/1.2 mmol/kg, transdermal 0 prodrug-isoniazid/prodrug-moxifloxacin/prodrug-π-pyrazine acid, 0.06/0.07/0.4mmol/kg, transdermal 4.23 0.55 Prodrug - Isoniazid / Prodrug - Moxifloxacin / Prodrug - Deuterium 11 Qin Acid, 0.06 / 0.07 / 0.4mmol / kg, transdermal 0 Table 9b. Cure rate results cure rate (%) Group treatment After 45 days of treatment, 90 days after treatment, blank group (A) 0/20 (0) 0/20 (0) isoniazid / moxifloxacin / pyrazinamide 2/20 (10) 0.18/0.22/1.2mmol/kg, mouth Isoniazid/moxifloxacin indoxazolamide 5/20 (25) 151 201143772 0.18/0.22/1.2mmol/kg, oral prodrug-isoniazid/prodrug-moxifloxacin/prodrug-pyridin Usaic acid 0-18/CK22/l, 2mmol/kg, transdermal 18/20 (90) prodrug - isoniazid / prodrug - moxifloxacin / prodrug azine acid 0.18/0.22/1.2mmol/kg, Transdermal 20/20 (100) Prodrug - Isoniazid / Prodrug - Moxifloxacin / Prodrug - β than citric acid 0 '06 / 0.07 / 0.4mmol / kg, transdermal 10 / 20 (50) Prodrug - Isoniazid / Prodrug - Moxifloxacin / Prodrug - ° phenazine acid, 0 '06 / 0.07 / 0.4mmol / kg, transdermal 20 / 20 (100) Example 1 〇, treatment of adult tuberculosis (children cut back Amount) 4〇mg N-(N-Mercapto-phenylalanine) isoniazid hydrochloride (prodrug _ isoniazid) / 50mg 1-cyclopropyl-7-[(ls,6S)-2 , 8-diazabicyclo[4.3.0] 壬院-8-yl]-6-fluoro-8-oxime-4-oxo-quinoline-3-carboxylic acid butyl ester hydrochloride (prodrug- Moxifloxacin)/4〇mg 2-pyrazinium n'N-diethylaminoethyl ester hydrochloride (prodrug-2-pyrazinecarboxylic acid) is dissolved in 3 ml of water and applied to the patient's chest or The skin of any other part of the body (near the infected organ), twice a day in the morning and evening, for 90 days or until recovery. Example 11 'treatment of leprosy or Hansen's disease in adults (HD) (child ... 152 201143772 child lower dose) 30 mg 4 - dimethyl gas based butyl amine base - 4 '- gas based benzene $ wind (prodrug Dapsone) / 50mg 1-cyclopropyl·7-[-(18,68)-2,8-diazabicyclo[4 3 〇] 壬-8-yl]-6-fluoro-8- Oxy-4-oxo-quinoline-3-carboxylic acid butyl ester hydrochloride _ (prodrug - moxifloxacin) / 15mg 2 (4-dimercaptoaminobutyric acid thiobenzoate π sitting (prodrug - benzene) Imidazole) is dissolved in 3 ml of water and applied to the skin of the patient's chest or any other part of the body (near the infected organ) twice a day, morning and evening for 6 months or until recovery. Example 12, treatment of ear infections 2 〇 mg 6-phenoxyacetamidine penicillin acid 2-diethylaminoethane hydrochloride is dissolved in 1 ml of water and applied to the patient's skin close to the infected ear (near the infected organ) 'every morning and evening twice' 2 weeks or until rehabilitation. Example I3, treatment of lower respiratory tract infection in adults (children's lowering agent • 8 〇 mg D-a_[(imidazolidine-2-one-1-yl)carbonylamino]benzylpenicillin 2-four Hydropyrrole methyl ester hydrochloride dissolved in 3 ml Apply to the skin of the patient's neck or chest (near the infected organ) twice a day in the morning and evening for 2 weeks or until recovery. Example 14 'Treatment of upper respiratory tract infection in adults (lower dose for children) 8〇^ng 6-D(-)-a_(4·ethyl 2,3_dioxosinoxazinylcarbonylamino)a phenethyl hydrazine aminopenicillic acid _2_diethylaminoethyl ester hydrochloride dissolved in 153 201143772 Apply 2 ml of water to the skin of the patient's neck (near the infected organ) twice a day in the morning and evening for 2 weeks or until recovery. Example 15 Treatment of upper respiratory tract infection in adults (lower dose for children) 30 mg3-[ [(Aminocarbonyl)oxy]methyl]_7_methoxy_8-oxothiophenylethyl)amino)]·5-thia-1-azabicyclo[4 2 〇]oct-2-ene • 2 Carboxylic acid 2·diethylaminoethyl ester hydrochloride is dissolved in 2 ml of distilled water and sprayed into the patient's mouth or nose, once in the morning and evening, for 2 weeks or until the sweet recovery. Example 16, Treatment of meningitis in adults (lower dose in children) 80 mg 6-D(-)-a-(4-ethyl-2,3-dioxo-1-pyridazinylamino)-a-benzene Ethylaminopenicillin acid 2_diethylaminoethyl ester hydrochloride is dissolved in 3 ml of distilled water and applied to the skin of the patient's neck and head, once every morning and evening for 2 weeks or until recovery. Example 17, treatment of diarrhea-type dysentery (children's dose reduction) 80 mg of 7-(2-mercaptoethylamino) cephalosporanic acid 2-diethylaminoacetamide salt I salt in 3 mi of distilled water and applied to patients On the skin near the navel, every morning and evening, for 2 weeks or until recovery. Example 18, treatment of breast infection 5 〇 mg ?·[(Zhao phenethyl)amino]·3_[[(1-methyl-lH-izgazole _5_ soil) claw] thiol] oxo-5_ Thia small azabicyclo[4 2 〇] 辛_2_烤_2_"

t b. J 154 201143772 Carboxylic acid 2-diethylaminoethyl ester. The hydrochloride salt is dissolved in 2 mi of distilled water and applied to the skin around the patient's breasts 'every morning and evening, for 2 weeks or until recovery. Example 19, treatment of male or female reproductive system infection (children's dose reduction) 8 〇 mg 3-[[(aminocarbonyl)oxy]indolyl]_7_[[2_furanyl(oxiranimido)ethylamino] -8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-acid 2-ethylaminoethyl g hydrochloride salt dissolved in 3 ml of water 'will It is applied to the patient's affected area, once in the morning and evening, for 2 weeks or until recovery. [Simple description of the diagram] Figure lal shows 6_phenoxyethylaminopenicillin-2-diethylaminoethyl ester isolated from human skin tissue isolated in a vertical test diffusion permeameter (Franz ceUs) (; n=5) Hydrochloride (A), propylene thiomethyl penicillin acid 2_didecylaminoethyl ester hydrochloride (B) '6-(2,6-dimethoxybenzamide;) penicillin-2 -diethylaminoethyl ester hydrochloride (c), 6_(5_mercapto_3_phenyl_2_isoacesulfame-4-indoleamine) penicillin acid_4_狐德定乙g Hydrate (d), 6-[3-(o-chlorophenyl)-5-methyl-4-isoxazolecarbamidine] penicillin acid _3_ acridine ethyl ester hydrochloride (E), 6-[3-(2,6-diphenyl)-5-methyl-4-isoxazolecarbamoyl]penicillin _ 1 _ acridine ethyl ester hydrochloride (F ), penicillin V (G) ), the cumulative total amount of penicillin 0 ( Η ), methicillin (j ), benzoxazole, penicillin (j ), phthalic acid (Κ), and penicillin (B). In each of the examples, the carrier solution was a phosphate buffer solution (0.2 M) of pH 7.4. Figure la2 shows 6_[D(_)_a_aminophenethylamine]penicillin ethyl ester hydrochloride of human skin tissue isolated by a vertical test diffusion permeameter (Franz ceUs) 155 201143772 (n=5) A), Da-[(imidazol-2-one-indolyl)carbonylamino]benzylpenicillin-2-pyrrole methyl ester hydrochloride (B), 6r_[2_[3_(methylsulfonyl)-2-oxo -1--1-imidazolidinecarboxamido]_2_phenethylamino]penicillin acid pyrrole ethyl ester hydrochloride (C), 6-D(1)-a-(4_ethyl_2,3_dioxo _丨_呱azinemethyl)-a-phenethyl hydrazine, penicillin acid diethylaminoethyl ester hydrochloride (D), 7-(2-thienyl oxime amino) cephalosporanic acid 2-di Cumulative total amount of ethyl ester hydrochloride (E), ampicillin (F), azlocillin (G), mezlocillin (h), _ guarcillin (I) and cephalosporin (1) . In each case, the carrier solution was a phosphate buffer solution (〇 2M) of pH 7.4. Figure 1 a3 shows 7_[(hydroxyphenylethyl)amino]-3-[[(l-曱基·1Η-) of human skin tissue isolated by a vertical test diffusion permeameter (Franz) (n=5) Tetras-5-yl)thio]methyl]_8_oxo_5_thiazepinebis(4.2.0]oct-2-ene-2-sodium 2-ethylaminoethyl ester Acid salt (Α), 3-[[(aminocarbonyl)oxy]indolyl]_7_[[2_furanyl(phosphonium imino) anthraceneamino]-8_oxo-5-thia-1 -azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 2-2-diaminoethyl ester hydrochloride (Β), 3_[[(aminocarbonyl)oxy]methyl methoxy-8 _oxo·7_[(2·嗟 基 醯 醯)amino)]_5_thia-1-ylheterobicyclo-[4.2.〇]_oct-2·ene·2_carboxylic acid 2_diethyl Aminoethyl ester hydrochloride (C) '7·[[[2_(Ethylaminomethyl)phenyl]ethinyl]amino]3_[[Π-(ethoxycarbonylindolyl)·1Η_tetrazole _5 yl] thio] fluorenyl] oxo-5-thiathiazepinebicyclo[42〇]octyl-2-ene-2-hydronic acid 2_diethylaminoethane hydrochloride (D), 7_[(乙苯苯苯醯)Amino]·3·Ga-8-oxo sulphur+azabicyclo ring (1) 辛^缓酸^二

Is] 156 201143772 Accumulation of ethyl acetate hydrochloride (E), ceftimedo (F), cefuroxime (G), cefoxitin (H), ceftrid (1), and cefaclor (J) Total amount. In each case, the carrier solution was a phosphate buffer solution (〇 2 M) of pH 7_4. Figure la4 shows 3_[(ethoxycarbonyl)methyl]_7-[[ (2-ethylamino)_4 of human skin tissue isolated by vertical test diffusion osmosis apparatus (n-5) _thiazolyl)(methoxyimino)ethinyl]amino]-8.oxo_5_thiazepine_azabicyclo[4.2.〇]oct_2_ene_2_carboxylic acid 2_ Diethylaminoethyl ester hydrochloride (A), 7-[[(2-acetamido-4-4 thiazolyl)(曱 oxyimino)ethinyl]amino]_8_oxo_5_sulfur Hetero-1_azabicyclo[4.〇]oct-2-ene-2-carboxylic acid 2-diethylaminoethyl ester hydrochloride (B), ethyl-2,3-dioxo-y _ oxazine)carbonyl]amino]_(4_acetoxyphenyl)ethyl hydrazide]amino]-3-[[(l-fluorenyl-1H-tetrazol-5-yl) thio] fluorenyl] ·8_oxo_5_thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 2-diethylaminoethyl ester hydrochloride (C ) ' 7-[2- (2-Ethylamino-4-indolyl)_2-((ζ)-曱 亚 亚 ) ) ) 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯 醯_丨·Azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 2-diethylaminoethyl ester hydrochloride (D), 7-[2-(2-Ethylamino-4- Thiazole)-2-((Z)-ethoxycarbonylcarbonyloxy Imino] ethanesulfonyl]-3-(ethyl:fcfyl)-8-oxo-5-thiato_methane-heterobicyclo[42.0]oct-2-ene-2-deconazole 2-one Ethylaminoethyl ethane hydrochloride (E), cephalosporin. The cumulative total amount of cefotaxime (G)' cefotaxime (H), cefpodoxime (1), and cefixime (J). The carrier solution was a pH 7 4 phosphate buffer solution (0.2 M). Figure lb shows [2S-(2a,3p,5a)]-3-mercapto-7-oxo-r 157 201143772 ·3-(1Η·1'2,3·azidomethyl)_4•thio Azabicyclo[3,2,〇]heptane-2-carboxylic acid 4,4-dioxide (tazobactam, curve f), [2S-(2ct,3p,5a)]-3-A Base oxo·3_(1Η_12 3 azidomethyl)_4_thio-1-azabicyclo[3,2,〇]heptane-2-carboxylic acid-dioxide^ acridine ethyl ester hydrochloride (Taxazole &amp; ΡΕΕ, curve A), (2S, 5r)_3,3-dimethyl-7-oxo-4·thia+azabicyclo[3·2〇]Gengyuan_2_slow acid _4,4· sodium dioxide (sulbactam, curve G), (2S, 5R)_3,3-dimethyloxo-4-thia-1-azabicyclo[3,2,〇]g Sodium alkane-2-carboxylate·4,*•di-oxide Ν, Ν-diethylaminoethyl hydrazine hydrochloride (sulbactam _dee, curve) (2R, 5R, Z) 3-(2- ^乙浠基)_7_氧代_4_oxato_ι_aza-bicyclo[3.2.0]-heptane-2-carboxylic acid (clavulanic acid_curve, (211,511,2)_3_( 2_ via vinyl) _7_oxo_4_oxathiazepine-bicyclo[32.〇]_heptane l-acid 4-51 melon 疋 曰 曰 曰 ( ( ( ( ( ( ( Curve c), [(N_卞oxyaminoamino) Sodium]-phosphonic acid mono-(4-nitrophenyl) ester sodium salt (curve n, [(anthracene oxycarbonylamino) fluorenyl]-phosphonic acid nitrophenyl) (n, N-diethyl Aminoguanidino). hydrochloride (curve D) '[(N-oximeoxycarbonylamino)methyl]-phosphonic acid mono-(3-«-pyridyl) ester sodium salt (curve j) and [( The cumulative total amount of N_卞 oxycarbonylamino)methylphosphonate pyridyl) 〇-acridinyl) ester hydrochloride (curve E) through the human skin in the Franz pool (n=5). The carrier solution was 〇 2M phosphate buffer solution at pH 7.4. Figure lc shows the curve as 4_amino sulfonamide (p-amino sulfonamide 'E) ' 4-(4-dimercaptoaminobutyl decyl) amino benzene sulfonamide hydrochloride (DMAB-p-amino group) Phenylxanthine, a), 6-oxo-3-(2-[4-(7V-0) deg-2-ylsulfonyl) stupid]-linked amino) cyclohexanthene, 4-dienecarboxylic acid '6_oxo S S i 158 201143772 -3-(2-[4-('° pyridine-2· sulfamoyl) phenyl] hydrazine amino) cyclohexyl hydrazine —diene carboxylic acid (sulfasalazine, F), 6_oxo_3_(2_[4_(Λ^pyridine-2-aminosulfonyl)phenyl]-linked amino)cyclohexanyl, 4_ Bismuth diene carboxylate, hydrazine-diethylaminopropyl ester hydrochloride (sulphonium sulfapyridine pyridine) (1) 艮Β), 丨_cyclopropyl _6· fluoro-4-oxo-7- Pyridazin-1-yl-quinolinecarboxylic acid (ciprofloxacin, G), cyclocyclopropyl-6-gas-4-oxo-7_, guzinyl-3-3-decanoate hydrochloride ( Ciprofloxacin-BE' C), 1-ethyl-7-mercapto-4-oxo-[U]naphthyridin-3carboxylic acid (naphthyridinic acid, hydrazine), 1-ethyl-7- The cumulative total of thiol-4-oxo-[L8]naphthyridinium-3-carboxylic acid succinyldiethylaminoethyl sulfonium salt (Qin sulphate) passed through the human skin in the Frannz pool Quantity (n=5). What is the carrier solution? 1^ value 74 〇.2M phosphate buffer solution. [Main component symbol description]

159

Claims (1)

201143772 VII. Patent application scope: or a combination of high permeability of antibacterial agent phase 阙 compound; a functional unit; a connector; and a transport unit; the functional unit is covalently connected to the transport unit through the linker. The moiety containing an antibacterial or antibacterial agent-related compound has a protonatable amino group; and the linker contains a chemical bond which is cleaved after the high permeability composition has permeated through a layer of biological barrier.夕 2. If you apply for a patent range! The high permeability composition of the present invention, wherein the bond is selected from the group consisting of a covalent chemical bond '(iv), a sulfur _, a uranium bond, a sulphur vinegar bond, a carbonated vinegar bond, a urethane bond, and a hydrazine bond.曰埏 The high permeability composition of claim 1, wherein one of the antimicrobial agents or the antibacterial agent-related compound can be converted into an antibacterial agent or an antibacterial agent-related compound by lysis of the cleavable bond. 4. The high permeability composition of claim 1, wherein the unit comprises a lipophilic derivative of a portion of a beta-nemoamine antibiotic or a ρ-lactam antibiotic related compound. The high-permeability composition of claim 4, wherein the lipophilic derivative is selected from the group consisting of carbonated vinegar, hydrazine, amide, uric acid vinegar, N-_nich domain, (10), Sulphur scale m dance vinegar, will be amine. 6. The high permeability composition according to claim 4, wherein the P-endoamine antibiotic or the intrinsic antibiotic related compound is selected from the group consisting of β-(tetra)amine antibiotics, p_inner axis Antibiotic metabolites and agents that can be metabolized into beta-endoleamine antibiotics and analogs thereof. 7. The high permeability composition of claim 1, wherein the protonatable amino group is selected from the group consisting of substituted and unsubstituted 'grades: substituted and unsubstituted secondary amino groups, and substituted and unsubstituted The di-ammonia 8. The high-permeability group of the invention as recited in claim 7 wherein the protonatable amino group is selected from the group consisting of: W-1, structural formula W-2, structural formula w_3, knot, , '. Structure W-5, Structure W_6, Structure, Name W-8, Structure W-9, Structure w_ •, K-11, Structure W_12, Structure w: Structure W-14 , structural formula W_15, structural re-formation knot -V W-17 and structural W-18, % 161 201143772 Structural Formula W-1 Structural Formula W-2 Structural Formula W-3 Structure W-4 Structure W-5 Structure W-6 Xin Structure W-7 Structure W-8 Structure W-9 Structure W-10 Structure W-11 Structure 162 201143772 W- 1 2 Structure w- 1 3 Structure W- 1 4 Structure W- 1 5 Structural Formula W-16 Structural Formula W-17 Structure # Formula W-18, including stereoisomers and pharmaceutically acceptable salts thereof, wherein: HA is selected from the group consisting of: none, hydrochloric acid, hydrobromic acid, hydrogen iodine Acid, nitric acid, sulfuric acid, sulfurous acid, phosphonic acid, sub-acid, wall acid, isonicotinic acid, acetic acid, lactic acid, salicylic acid, citric acid, tartaric acid, pantothenic acid, acid tartaric acid, ascorbic acid, succinic acid, maleic acid , gentianic acid f 163 201143772 (gentisinic acid), fumaric acid, gluconic acid, gluconic acid (glucaronic acid), sugar acid, citric acid, benzoic acid, glutamic acid, mineral acid, acetyl acid, benzene sulfonic acid , p-toluenesulfonic acid and pamoic acid; R is selected from the group consisting of: no, hydrazine, CH 2 COOR 6 , substituted and unsubstituted hydrocarbyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, substituted and Unsubstituted alkoxy groups, substituted and unsubstituted polyfluorohydrocarbyl groups, substituted and #unsubstituted il-hydrocarbyl groups, substituted and unsubstituted alkenyl groups, substituted and unsubstituted alkynyl groups, substituted and unsubstituted aryl groups, and Substituted and unsubstituted heteroaryl, wherein any of R Wherein CH2 may be replaced by hydrazine, S, P, NR6 or any other pharmaceutically acceptable group; R1 - R2 may be independently selected from the group consisting of hydrazine, substituted and unsubstituted hydrocarbon groups, substituted and unsubstituted rings, respectively. Hydrocarbyl, substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted alkoxy, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, and substituted and unsubstituted Heteroaryl; R5 is selected from the group consisting of hydrazine, -CONH2, CH2CH2OR6, CH2CH2N(CH3)2, CH2CH2N(CH2CH3)2, C1, F, Br, I, substituted and unsubstituted hydrocarbyl groups, substituted and unsubstituted Cycloalkyl, substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted alkoxy, substituted by 164 201143772 unsubstituted cycloalkoxy, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, Substituted and unsubstituted hydrocarbon carbonyls, substituted and unsubstituted hydrocarbon amino groups, -COW, LJ-L4-L2-W and W; R6 is selected from the group consisting of ruthenium, F, Cl, Br, I, Na+, K+, COR5 , 2-oxo-1-imidazolidinyl, phenyl, 2-oxo-1-°m2-(i-oxo-l-imidazolidinyl), phenyl ( Mouth 11611&gt;^1), 5-indanyl (5_111(1&amp;11&gt;^1), 2,3-dihydro-hydrogen-inden-5-yl (2,3-dihydro-lH-inden- 5-yl), 4-cyano-1,5-naphthyridin-3-yl, substituted and unsubstituted hydrocarbyl, substituted and unsubstituted cycloalkyl, Substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted | and unsubstituted alkoxy, substituted and unsubstituted cycloalkoxy, substituted and unsubstituted Aryl, substituted and unsubstituted heteroaryl, -C(= Ο) - W, L 1 - L 4 - L 2 - W and W; R 1 1 -1 6 are each independently selected from the group consisting of: , CH 2 C Ο Ο R i !, substituted and unsubstituted hydrocarbyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted alkoxy, substituted and unsubstituted polyfluoro Hydrocarbyl, substituted and unsubstituted halohydrocarbyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted u L 〇i 165 201143772 and unsubstituted aryl and substituted and unsubstituted heteroaryl Li is selected from the group consisting of: None, 0, S -0-L3-, -S-L3-, -N(L3)-, -n(l3)-ch2-o, -n(l3)-ch2-n(l5)-, -o-ch2-o... -o-ch(l3)-o, and _s-ch(l3)-o; l2 is selected from the following groups: none, o, s, -o-l3-, _s_l3-, _n(l3)·, -n (l3)-ch2-o, -n(l3)-ch2-n(l5)-, -〇-ch2-o-,-0-CH(L3)-0,-S-CH(L3)-0- , -O-L3-, -N-L3-, -S-L3-, -N(L3)-L5 - and L 3, /OL3 n,ol3 N|/ L4 are selected from the group consisting of C = 0, C = S, -c - L5 -, one c and ο -P - ο -l5 - 01-3 ; Lu for each L 1, L 2, and L 4, L 3 and L 5 They may be independently selected from the group consisting of: none, hydrazine, CH2C(=0)0L6, substituted and unsubstituted hydrocarbyl groups, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted heterocycloalkyl groups, substituted and unsubstituted aryl groups. , substituted and unsubstituted heteroaryl, substituted and unsubstituted hydrocarbyloxy, substituted and unsubstituted hydrocarbylthio, substituted and unsubstituted hydrocarbylamino, substituted and unsubstituted polyfluorohydrocarbyl, and substituted and unsubstituted a halogenated hydrocarbon group in which any carbon or hydrogen atom can be substituted by hydrazine, S, P, NL3 or any accepting group, respectively, in a step of s 166 201143772; L6 can be independently Selected from the group consisting of H, OH, Cl, substituted and unsubstituted hydrocarbyl groups, substituted and hydrocarbyl groups, substituted and unsubstituted heterocyclic hydrocarbon unsubstituted aryl groups, substituted and unsubstituted substituted and unsubstituted hydrocarbyloxy groups, substituted a hydrocarbonthio group, a substituted and unsubstituted hydrocarbon ammonia Φ an unsubstituted polyfluorohydrocarbon group and a substituted and non-hydrocarbon group, wherein any carbon atom or hydrogen is further deuterated, s, N, P(0)0L6 c^c, chl6, Cl6l7, aryl, 3-like group substituted; L7 may be independently selected from the group consisting of H, OH, Cl substituted and unsubstituted hydrocarbyl, substituted and I hydrocarbyl, substituted and unsubstituted heterocyclic hydrocarbon unsubstituted aryl , substituted and unsubstituted substituted and unsubstituted alkoxy groups, substituted hydrocarbonthio groups, substituted and unsubstituted hydrocarbons, ammonia unsubstituted polyfluorohydrocarbon groups, and substituted and unsubstituted fe groups, wherein any carbon atom or hydrogen is further S, N, P(0)0L6 CeC, chl6, cl6l7, aryl, a substituted group; and other pharmaceutically acceptable F, B r, I, unsubstituted ring, substituted and heteroaryl, and Substituted, substituted and substituted halogen atoms may be respectively CH=CH, 隹aryl or ring, F, B r , I, unsubstituted cyclo, substituted and heteroaryl, and unsubstituted, substituted and substituted halo, respectively, CH = CH, fluorene or ring 167 201143772 W is selected from the group consisting of hydrazine, substituted and unsubstituted hydrocarbon groups, substituted and unsubstituted cyclic hydrocarbon groups, substituted and unsubstituted heterocyclic hydrocarbon groups, substituted and unsubstituted alkoxy groups, substituted and unsubstituted alkenyl groups, and substituted groups. And unsubstituted alkynyl groups, substituted and unsubstituted aryl groups, substituted and unsubstituted heteroaryl groups, structural formula Wa, structural formula W-1, structural formula W-2, structural formula W-3, structural formula W- 4. Structural formula W-5, structural formula W-6, structural formula W-7, structural formula W-8, structural formula W-9, structural formula W-1, structural formula W-1, structural formula W- 12. Structural formula W-13, structural formula W-14, structural formula W- 1 5. Structural formula W- 1 6. Structural formula W- 1 7 and structural formula W- 1 8. Structural Wa, Structural Formula W-1, Structural Formula W-2, Structural Formula W-3 168 201143772 Structure W-4 Structure W-5 Structure W-6 Structure W-7 Structure W-8 Structure W-9 Structure W- 1 0 Structure W- 1 1 Structure, W-1 2 HA Structure w- 1 3 Structure W- 1 4 Structure W- 1 5 169 201143772 Structure W-16 Structure W-17 Structure 9. A highly permeable composition having the following chemical structure: The structural formula L - 1 includes stereoisomers thereof and pharmaceutically acceptable salts thereof, wherein: F contains a part of a β-endoamine antibiotic or an antibiotic-related compound, which contains a structural formula selected from the group consisting of structural formula F _ 1, structural FP-1, structural FP-2, structural FP-3, structural FP-4, structural FP-5, structural FP-6, structural F Ρ - 7, structural F Ρ - 8, structural formula F Ρ - 9, structural formula F Ρ - 1 0, structural formula FP-1 1, structural formula FP-12, structural formula FP-13, structural formula FP-14, structural formula FP-15, structure Formula FP-16, structural formula F Ρ - 1 7. Structural formula F Ρ - 1 8. Structural formula F Ρ - 1 9. Structural formula FP-20 &gt; Structural formula F Ρ - 2 1. Structural formula F Ρ - 2 2. Structural type FP-23, structural type FP-24, structural type FP-25, structural type F Ρ - 2 6. Structural formula F Ρ - 2 7. Structural formula F Ρ - 2 8. Structural formula F Ρ - 2 9. Structural Formula F Ρ - 3 0, Structural Formula F Ρ - 3 1. Structural Formula FP-32, Structural Formula FP-33, Structural Formula FP-34, Structural Formula FP-35 &gt; Structural Formula F Ρ - 3 6 , Structural Formula F Ρ - 3 7. Structural Formula r 170 201143772 FP - 3 8. Structural Formula FP - 3 9. Structural Formula FP - 40, structural FP-41, structural FP-42, structural FP-43, structural FP-44, structural FP-45, structural FP-46, structural FP-4, structural FP - 4 8. Structural FP - 4 9. Structural FP-50 'Structural FP-5 1. Structural FP-52, Structural FP-53, Structural FP-54, Structural FP-55, Structural FP -56 'Structural FP - 5 7. Structural FP - 5 8. Structural FP-59 'Structural FP - 60 0, Structural FP - 6 1. Structural formula • FP-62, structural FP-63, Structural type FP-64, structural type FP-65 'Structural type FP-66, structural type FP-67, structural type FP-68, structural type FP-69, structural type FP-70, structural type FP-7 1, structure Formula FP-72, structural FP-73, structural FP-74, structural FP-75, structural FP-76, structural FP-7, structural FP-7, structural FP-7 Structural formula FP-8 0, structural FP-8 1, structural FP-82, structural Lu FP-83, structural FP-84, structural FP-85, structural FP-86, structural FI-1 Structural FI-2, Structural FI-3, Structural FI-4, Structural FI-5, Structural FI-6, Structural FI-7, Structural FI-8, Structural FI - 9. Structural formula FI - 1 0, structural formula FI-1 1, structural formula FI-12, structural formula FI-13, structural formula FI -1 4. Structural formula FI - 1 5. Structural formula FI - 1 6. Structure Formula FI - 1 7. Structural formula FI - 1 8. Structural formula FI - 1 9. Structural formula FI - 2 0, Structural formula FI - 2 1. Structural formula FI - 2 2. Structural formula FI - 2 3. Structural formula FI - 2 4, structural type FI - 2 5, structural formula f 171 201143772 FI - 2 6. Structural type FI - 2 7. Structural type FI - 2 8. Structural type FI - 2 9. Structural type FI - 3 0. Structural FI-3, structural FI-32, structural FI-33, structural FS-Bu structure FS-2, structural FS-3, structural FS-4, structural FS-5, structural formula FS - 6, structural FS - 7, structural FS - 8, structural FS - 9, structural FS - 1 0, structural FS - 1 1, structural FS-12 'structural FS - 1 3, structure Formula FS - 1 4, Structural Formula FS - 1 5, Structural Formula FS - 1 6. Structural Formula FS - 1 7. Structural Formula • FS - 1 8. Structural Formula FS - 1 9. Structural Formula FS - 2 0. Structure Formula FT-1, structural FT-2, structural FT-3, structural FT-4, structural FT-5, structural FT-6 Structural Formula FT-7, Structural Formula FT-8, Structural Formula FT-9, Structural Formula FT-10, Structural Formula FT-1 1 &gt; Structural Formula FT-1, Structural Formula FT-1, Structural Formula FT- 1 4. Structural formula FT- 1 5, and structural FT- 1 6, Structural Formula F - 1 Structural Formula F P - 1 Structural Formula FP-2 172 201143772 Structural FP-3 Structural FP-4 Construction FP-5 Structural Formula FP-6 Structural FP-7 Structural FP-8 173 201143772 Structural FP-9 Structural Formula F P - 1 0 Construction F P - 1 3 Structural Formula F P - 1 4 Structural formula F P - 1 5 Structural formula F P · 1 6 174 201143772 HA NH2 h2j LTL4-L2-R5 L31 ^34^32-^6 Structural Formula F - 1 7 Structural Formula FP- 1 8 丫3 Yi Vi Structural FP-1 Structural FP-20 Υ3 VT&gt; Structural formula FP-22 FP-2 1 structure 175 201143772 Structural FP-23 structure Structural FP-25 Construction FP-26 Reference Structural FP-27 Structural Formula F P - 2 8 176 201143772 Structural FP-29 Structural Formula F P - 3 0 Structural formula # Structure F P - 3 1 FP-32 Structural formula F P - 3 3 FP-34 177 201143772 Structural FP-35 Structure FP-36 Structural Formula F - 3 7 Structural Formula Structural Formula F - 3 9 Structure 178 201143772 Style FP-40 Structural Formula F - 4 1 Structure FP-42 Structural FP-43 Structure FP-44 Structural FP-45 structural formula [!j 1 179 201143772 FP-46 FP-48 FP-50 Structural Formula F P - 5 1 Structural Formula 180 201143772 FP-52 Structural FP-55 Construction FP-56 Structural FP-57 181 201143772 Structural Formula F - 5 9 Structure FP-60 Structural Formula F P - 6 1 Structure FP-62 Ν 182 201143772 Structural FP-63 Structural FP-64 Structural FP-65 FP-66 183 201143772 Structure FP-69 type FP-70 structure Structural Formula F P - 7 1 FP-72 Structural Formula χ5, H3C, 〇', ',, ',,, ..rv Structural formula FP-73 FP-74 184 201143772 Structural FP-75 Structural FP-76 Structural FP-77 structure Construction FP-80 Ch3 185 201143772 Structural Formula F P - 8 1 Structure FP-8’2 Y3- CHs ch3 Λ h2c Structural Formula F - 8 3 Structural Formula FP-84 Structural F P - 8 5 ik Construction FP-86 ^I^ X-w s 186 201143772 Structural FI - 1 Structural FI - 2 Structure Structural FI-5 Structural Type FI-4 Structural type FI-6 Structural formula Construction FI-8 Structural Formula FI - 9 187 201143772 Structural FI - 1 Ο Type FI-1 1 Structural FI - 1 2 Type FI-13 Structure F I - 1 4 Type FI-1 5 188 201143772 Structural FI - 1 6 Structural FI- 1 7 _ Structural Formula F I - 1 8 Type FI-19 Structural type FI-20 FI-2 1 189 201143772 Structural FI-2 2 type FI-23 structure Structural type FI-2 4 Type FI-25 Structure Φ Structure type FI-2 6 type FI-27 190 201143772 type FI-29 Structural Formula F I - 3 0 Structure Structural Formula F I - 3 2 Type FI-33 Structure F S - 1 type FS-2 [s] 191 201143772 Structural FS-3 Structural FS-4 FS-6 Structure FS-8 construction F S - 7 0-Re Υι [s] 192 201143772 Structural Formula FS-9 FS- 1 0 FS-13 Structural Formula F S - 1 4 Structural Formula F S - 1 5 Structure FS-16 193 201143772 Structural Formula F S - 1 7 Structural Formula F S - 1 8 Structural F S - 1 9 Construction FS-20 Structural FT- 1 ❿ FT-3 XX Structural FT-4 Structural FT-5 Structure 194 201143772 Structural FT-9 Structural FT- 1 0 195 201143772 Structural FT- 1 1 Structural FT- 12 Structural FT- 1 3 Structural formula FT-14 Structural formula FT-15 Structural formula FT-16, including its stereoisomers and pharmaceutically acceptable salts thereof; Y is selected from the group consisting of H, OH, NHCHO, NHC (= 0) R6, 0C ( = 0) CH3, 0C ( = 0) R6, OCH3, OC2H5, OR6, CH3S03, R6S03, N02, CN, CF3, OCF3, OC2F5, OC3F7, F, Br, I, Cl and substituted and unsubstituted oxygenated 196 201143772 Π \Selected from the following group: knot structure NS - 3, crusting structure NS - 1, structural NS - 2, construction NS - 4, and structural NS - 5 : ζ Conclusion Χ1 Construction NS-4 197 201143772 ' z Λ1 Structural formula NS - 5 Xi is selected from the group consisting of H, OH, OCH3, OC2H5, OR6, C( = 0)NH2, ch2oc( = o)nh2, ch2oc( = o )ch3 , ch2oc( = o)ch6 , • oc( = o)ch3, oc( = o)r6, CH2OCH3, CH3, C2H5, R6, Cl, F, Br, I, HC = CHCH3, HC = CH2, CH2OCH3 , CH2OR6 , S(CH2)n-NHR7, structural formula X^l, structural formula X ! - 2, structural formula X i - 3, structural formula X i - 4, structural formula X i - 5, structural formula X ! 6, structural formula X! - 7, structural formula X! - 8, structural formula X! - 9, structural formula X i -1 0, structure ^ formula X ! -1 1, structural formula X ! -1 2, structural formula X i - 1 3, structural formula X!-14, structural formula Xi-15, structural formula X! -1 6. Structural formula X! - 1 7. Structural formula X, -1 8. Structural formula X ! -1 9 Structural formula X i - 2 0, structural formula X i - 2 1 , structural formula Χ γ 22 , structural formula X ! -23, structural formula X i - 2 4 , structural formula X ! - 2 5 , structural formula X i - 2 6, structural formula X! - 2 7, structural formula X! - 2 8, structural formula X! - 2 9, structural formula X 1 - 3 0, structural formula X ! - 3 1, structural formula X ! - 3 2 Structural formula X i - 3 3 Structural formula X ! - 3 4, knot [ 198 201143772 Construction X ! - 3 5 , Structural formula X i · 3 6, Structural formula X ! - 3 7 , Structural formula X! -38, Structural formula Xr39, Structural formula X - 4 0, Structural formula X ! - 4 1. Structural formula X i - 4 2. Structural formula X i - 4 3. Structural formula X ! - 4 4. Structural formula X i - 4 5. Structural formula X!- 46, structural formula Xr47, structural formula X i - 4 8, structural formula X i - 4 9, structural formula X i - 5 0, structural formula X, - 5 1, structural formula X! - 5 2, structural formula X! - 5 3. Structural formula Xr54, structural formula 55^55, structural formula X ! - 5 6. Structural formula X i - 5 7. Structural formula X ! - 5 8. Structural formula X i - 5 9. Structural formula X ! - 6 0, Structural formula X ! - 6 1. Structural formula Xi- 62. Structural formula Xr63, structural formula X! - 6 4. Structural formula X i - 6 5. Structural formula X, - 6 6. Structural formula X i - 6 7. Structural formula X ! - 6 8. Structural formula X ! - 6 9. Structural Xi-70, structural Xi-71, structural formula X i - 7 2. Structural formula X ! - 7 3. Structural formula X i - 7 4. Structural formula X ! - 7 5. Structural formula X ! - 7 6. Structural formula X , - 7 7. Structural formula Χ γ78, Structural formula 79^79, structural formula X i - 8 0, structural formula X i - 8 1 and structural formula X 1 - 8 2, Structure X 1 -1 Structural Formula X 1 - 2 Structural Formula X 1 - 3 199 201143772 Formula X i - 6 Structural Formula X Structural Formula X X2 Structural formula X 1 - 9 \ N=:N H2C-IN, -R5 'u Structural formula X 1 -1 〇 H2C——N Rs Structural formula X i -1 1 Structural formula X i - 1 2 200 201143772 Xi-13 Structure X 1 -1 4 Structural formula X ! -1 7 Structural formula X ! -1 8 201 201143772 Structure X ! -1 9 Structure X ! - 2 0 Formula X ! - 2 1 Structure X ! - 2 2 Structure X ! - 2 3 Structure X ! - 2 4 [S] 202 201143772 -γ3 Structural Formula X 1 - 2 5 Structural Formula X ! - 2 6 Υι Configuration X i - 2 7 Structural Formula X i - 2 8 H2 /C, R&amp;0 ch〆 R60 CH \〇 NH-AA structure Χ,-29 HN——AA H3C\h/^ o NhM knot 203 201143772 OMe H2 structure Χ,-33 Structure X ! - 3 4 Formula X!-37 Structural Formula X i - 3 8 204 201143772 Γ2 Xi-39 Structure X i - 4 0 Structural formula X i - 4 1 Structural formula X ! - 4 2 Structural formula X!-43 Structural formula Xr44 Structural formula Xr45 Y2 Re r5 c^=c Yi Y2 Nhr7 structure type X!-46 structure type X i - 4 7 205 201143772 Ο 丫3 ο 〇〆 ch2 R5 R5 y2 ύ3 Viy2 Rs, 丫4 Structure X!-48 nr8 o nhr7 , Xs- Xi^X NR38 y2 o nr37 Construction X i - 5 0 Vi Structural formula X i - 5 1 Formula X i - 5 2 Structural Formula X ! - 5 3 Structural Formula Xj-54 ^L7 206 201143772 Style X i - 5 5 Structure X ! - 5 6 Structure X!-57 〇r8 N YiC Structure Structure X i - 5 9 Y2 structure structure X i - 6 1 # Υι Formula X1 - 6 2 Structure Χι_63 Structure Χι·64 207 201143772 Formula X]-65 X35 Χ5 208 201143772 Construction X ! - 7 3 Structure X , - 7 4 Formula Xr79 209 201143772 so2nh2 Formula X!_81 Structural formula X i - 8 2 ; 1 together with Y is R6OCH2C(R5)=, or itself selected from the group of sub-groups: R600CCH(NHR7)(CH2)nC(=0)NH·, R6OOCCH( NHR7)(CH2)nSC( = 0)NH-, CF3SCH2C( = 0)NH-, cf3ch2c( = o)nh-, CHF2SCH2C( = 0)NH-, CH2FSCH2C( = 0)NH-, nh2c( = o) Chfs-ch2c( = o)nh-, r7nhch(c( = o)ow)ch2sch2c( = o)nh-, R7NHCH(L1-L4-L2-W)CH2SCH2C( = 0)NH- 'CNCH2SCH2C( = 0) NH- ' CH3(CH2)nC( = 0)NH- &gt; [s] 210 201143772 R7N = CHNR7CH2CH2S-, r7n = c(nhr7)nhc( = o)-, r7n = c(nhr7)nhc( = o) Ch2, CH3C(C1) = CHCH2SCH2C( = 0)NH-, (CH3)2C(OR6)-, CNCH2C(=0)NH-, CNCH2CH2S-, R7HN = CH(NR7)CH2CH2S-, ch2 = chch2sch2c( = o Nh-, CH3CH(OH)-, CH3CH(OR8)- &gt; CH3CH(Y1)- '(CH3)2CH- 'CH3CH2-, CH3(CH2)nCH = CH(CH2)mC( = 0)NH-, Wherein n or m is a rational number greater than 0, structural formula Rs-1, structural formula Rs-2, structural formula Rs-3, structural formula Rs-4, structural formula Rs-5, structural formula Rs-6, structural formula Rs- 7. Structural formula Rs-8 211 201143772 Structural formula R s - 9, structural formula R s - 1 0, structural formula R s - 1 1. Configuration Rs-12, structural formula Rs-13, structural formula Rs-14, structural formula R s - 1 5 , structural formula R s - 1 6 , structural formula R s - 1 7 , structural formula R s - 1 8, Structural formula R s · 1 9 , structural formula R s - 2 0, structural formula Rs-2 1, structural formula Rs-22, structural formula Rs-23, structural formula Rs-24, structural formula Rs-25, structural formula Rs -26. Structural formula R s - 2 7. Structural formula R s - 2 8. Structural formula R s - 2 9. Structural formula Rs-30, structural formula Rs-3 1. Structural formula Rs-32, structural formula « R s - 3 3, structural formula R s - 3 4, structural formula R s - 3 5, structural formula R s - 3 6. structural formula R s - 3 7. structural formula R s - 3 8. structural formula R s - 3 9. Structural formula R s - 4 0, structural formula R s - 4 1. Structural formula Rs-42, structural formula Rs-43, structural formula Rs-44, structural formula Rs-45 [Si 212 201143772 And structural Rs-46, 丫3 structural formula Rs-3 structural formula Rs-4 Structural formula Rs-5 CONH structural formula Rs-6 213 201143772 Structural formula Rs-9, structural formula R s - 1 0 CONH structure Rs-ll structure Rs -1 2 214 201143772 Structure Rs-13 OCHO • A%-^c〇nh Structure R s - 1 4 or7 Y1 CONH Γ3 structure formula Rs- 1 5 structural formula Rs- 1 6 Formula Rs-1 7 Structural Formula Rs-1 8 'CONH- , NHRr C H2 215 201143772 Structural Formula Rs-19 Structural Formula Rs-20 ?-c〇Nh Structural formula Rs-2 1 Structural formula Rs-22 Rs-2 3 structural formula Rs-24 Structural formula Rs-25 Structural formula Rs-26 216 201143772 Formula Rs-27 Structural Formula Rs-28 Y2 structure R s - 2 9 structural formula R s - 3 0 Rs-31 CONH- COOW structure structure R s - 3 2 217 201143772 Ch3 Ch3 Ch3 Structure CONH Rs-35 Structural formula R s - 3 6 Rs-37 Structural Formula R s - 3 8 218 201143772 Υι Υι Y3 Y2 Rs-39 structural formula Rs-40 Structural formula R s - 4 1 Structural formula Rs-42 219 201143772 Structural formula Rs-43 Structural formula Rs-44 Structural Formula Rs-45 Structural Formula R s - 4 6 ; W is selected from the group consisting of hydrazine, substituted and unsubstituted hydrocarbon groups, substituted and unsubstituted cyclic hydrocarbon groups, substituted and unsubstituted heterocycloalkyl groups, substituted and unsubstituted Alkoxy groups, substituted and unsubstituted alkenyl groups, substituted and unsubstituted alkynyl groups, substituted and unsubstituted aryl groups, substituted and unsubstituted heteroaryl groups, structural formula Wa, structural formula W-1, structural formula W -2, structural type W-3, structural type W-4, structural type W-5, structural type W-6, structural type W-7, structural type W-8, structural type W-9, structural type W-1 0, structural formula W- 1 1, structural formula W- 1 2, structural formula W- 1 3, structural formula W- 1 4, 220 201143772 Structural formula W-1, structural formula W- 1 6, structural formula W- 1 7 and structural formula W- 1 8, Structural Wa, Structural Formula W-1, Structural Formula W-2, Structural Formula W-3 Structure W-4 Structure W-5 Structure W-6 Structure W-7 Structure W-8 Structure W-9 221 201143772 Structure w-10 Structure W-11 Structure W-1 2 Structural formula w-13 Structural formula W-14 Structural formula W- 1 5 Structural formula W-16 Structural formula W-17 Structural formula W- 1 8 ; Z is selected from the group consisting of CH2, S, SO, S02, NH, NR6, CHCH3, CHCH2CH3, CR6, R6, -c(=o) and 0 ; rrta 222 201143772 AA represents any amino acid; each m and η can be independently selected from the group consisting of 0 and an integer; ΗΑ is selected from the group consisting of: no, hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, sub Sulfuric acid, phosphonic acid, phosphorous acid, phosphoric acid, isonicotinic acid, acetic acid, lactic acid, salicylic acid, citric acid, tartaric acid, pantothenic acid, acid tartaric acid, ascorbic acid, succinic acid, maleic acid, gentian acid, Yanhu Russoic acid, gluconic acid, glucaronic acid, sugar acid, citric acid, benzoic acid, glutamic acid, phthalic acid, sulfonic acid, benzoic acid, p-toluene acid and pamoic acid; R is selected from the group consisting of: none, hydrazine, CH2C(=0)0R6, substituted and unsubstituted hydrocarbyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted | alkoxy , substituted and unsubstituted polyfluorohydrocarbyl, substituted and unsubstituted il hydrocarbyl, substituted and Substituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl, wherein any CH2 in R can be oxime, S, P, NR6 or any other pharmaceutically acceptable Substituted accepting groups; R 1 - R3 may be independently selected from the group consisting of hydrazine, substituted and unsubstituted hydrocarbyl groups, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted heterocycloalkyl groups, substituted and unsubstituted Hydrocarbon 223 201143772 oxy, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl; R5 and R35 may each independently be selected from Group: Η, c( = o)nh2, CH2CH2OR6, CH2CH2N(CH3)2, CH2CH2N(CH2CH3)2, Cl, F, Br, I, substituted and unsubstituted hydrocarbyl, substituted and unsubstituted cycloalkyl, substituted and Unsubstituted heterocycloalkyl, substituted and unsubstituted alkoxy, substituted and unsubstituted cycloalkoxy, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted hydrocarbon Carbonyl, substituted and unsubstituted hydrocarbon amino groups, -C(=0)-W, IM-L4-L2- W and W; R6, R3 6 and R46 can be independently selected from the group consisting of hydrazine, F, Cl, Br, I, Na+, Κ+, C(=0)R5, 2-oxo-1-I imidazole Alkyl, phenyl '2-oxo-1 -imidazolidinyl (2-0X0 -1-imidazolidinyl) 'phenyl (phenyl), 5-indanyl (5-丨11(1311)^1), 2 ,3-dihydro-monohydro-l-inden-5-yl, 4-hydroxy-l,5-na--3-yl- 4-hydroxy- l,5-naphthyridin-3-yl), substituted and unsubstituted hydrocarbyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl And take $ s 224 201143772 and unsubstituted alkoxy groups, substituted and unsubstituted oxy groups, substituted and unsubstituted aryl groups, substituted and substituted heteroaryl groups, -c(=0)-w, Lrl^- LKW and R7 and R37 can be independently selected from the group consisting of Η, F, Br, I, CH3NHC(= 0)CH2CH(NHR8)C( = r5n = c(nhr6)nhc( = o)-, c( = o) ch3, C(=0)R6, PO(OR5)〇R6, substituted and unsubstituted hydrocarbyl, substituted and unsubstituted cycloalkyl, substituted 0 substituted heterocyclo, substituted and unsubstituted hydrocarbyl, substituted and unsubstituted Substituted alkenyl, substituted and unalkynyl, substituted and unsubstituted aryl, substituted substituted heteroaryl, substituted and unsubstituted hydrocarbon substituted and unsubstituted hydrocarbon amino, LM-L4-L2-W C ( = 0)-W ; R8 and R38 can be independently selected from the group consisting of Η, F, • Br, I, CH3, C2H5, CF3, CH2CH2F, CH2CH2C1, CH2CH2Br, CH2CH2I, CH2CHF2, CH2CF3 - CH2F, CH2C CH2 ch2i, ch2nr6r7, ch(nhr7)ch2c( = o)nh2, c3h7, c4h C5Hh, r6, c( = o)r6, c( = o)nh2, ch2c( = o)nh2, CH20C( = 0)NH2 , PO(OR5)OR6, C(CH3)2C(=0)0R6, ch(ch3)c(=o)or6, ch2c(=o)or6, cyclic hydrocarbons not taken; w, o), generation And oxy-substituted and unsubstituted, and C1, Br, 9, 225 201143772 C(=0)-W, LM-L4-L2-W and W, substituted and unsubstituted hydrocarbyl, substituted and unsubstituted cycloalkyl, Substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted polyfluoroalkyl, substituted and unsubstituted hydrocarbyloxy, substituted and unsubstituted hydrocarbylamino, substituted and unsubstituted polyfluorohydrocarbyl, substituted and unsubstituted il Hydrocarbyl and substituted and unsubstituted hydrocarbons R 1 1 - R 1 6 are each independently selected from the group consisting of: none, hydrazine, # CI^CPCOORh, substituted and unsubstituted hydrocarbyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, substituted And unsubstituted alkoxy groups, substituted and unsubstituted polyfluorohydrocarbyl groups, substituted and unsubstituted halohydrocarbyl groups, substituted and unsubstituted alkenyl groups, substituted and unsubstituted alkynyl groups, substituted and unsubstituted aryl groups, And substituted and unsubstituted heteroaryl; ▲ X is selected from the group consisting of: none, C(=0), 0C(=0), CH2, CH, S, NH, NR6, and Ο; Group: none, H, CH2(CH2)nOR8, Cl, F, Br, I, N02, CN, CF3, C2F5, C3F7, OCF3, OC2F5, NH2, NHR6, CH3, C2H5, R6, c( = o)nh2 , CH20C(=0)NH2, CH2C(=0)0R5, CH2(CH2)nN(CH3)2, CH2(CH2)nS03R5, substituted and unsubstituted polyfluoroalkyl, substituted and unsubstituted hydrocarbyl, substituted and unsubstituted Substituting 226 201143772 for a hydrocarbonthio group, a substituted and unsubstituted hydrocarbon amino group, and a substituted and unsubstituted alkoxy group; x3 is selected from the group consisting of: none, H, N3, S03w, F, CM, Br, OH, OCH3, or6 , ch3, r6 c( = o)ow, OW, LiH-W and I; X4 is selected from the group consisting of: none, N, CH and CYl; X5 and X35 are each independently selected from the group consisting of: none, c( = o), 0C ( = 0), CH2, CH, S, Ο and NR5; # X6, X36 and X46 can be independently selected from the following groups: none, C(=0), 0C(=0), CH2, CH, S, 0 and NR5 ; X 7 can be independently selected from the following groups: none, C (= O), 0C (= 0), CH2, CH, S, ο, and nr5: Yi, Y31, Y2, Y32, Y3, and Y4 are independent Selected from the following groups: Η, OH, OW, 0C (= 0) W, LJ-L4-L2-W, 0C (= 0) CH3, CH3, C2H5, C3H7, C4H9, • R6, S03R6, CH2OR6, ch2oc ( = o)r6, CH2C( = 0)0R8, OCH3, OC2H5, OR6, CH3S02, R6S02, CH3S03, R6S03, N02, CN, CF3, OCF3, CH2(CH2)nNR5R6, CH2(CH2)nOR6, CH(C( = 0)NH2)NHR6, CH2C( = 0)NH2 F, Br, I, Cl, CH = CHC( = 0)NHCH2C( = 0)0W, CH = CHC( = 0)NHCH2L1-L4-L2-W ' Nr8c(=o)r5, so2nr5r8, c(=o)r5, SR5, m 227 201143772 Substituted and unsubstituted polyfluorohydrocarbyl, substituted and unsubstituted hydrocarbyloxy, substituted and unsubstituted hydrocarbylthio, substituted and Unsubstituted hydrocarbon amino Substituted and unsubstituted polyfluorohydrocarbyl groups, substituted and unsubstituted hydrocarbyl groups and substituted and unsubstituted hydrocarbon carbonyl groups; L1 and L 3 i may be independently selected from the group consisting of: none, 0, S, -〇-l3 -, -s-l3-, -n(l3)·, -n(l3)-ch2-〇, -N(L3)-CH2-N(L5)-,-0-CH2-0-, # -0 -CH(L3)-0 and -S-CH(L3)-0-; l2 and l32 can be independently selected from the group consisting of: none, o, s, -〇-l3-, -s-l3-, - n(l3)-, -n(l3)-ch2-o, -N(L3)-CH2-N(L5)-, -0-CH2-0-, -0-CH(L3)-0, -S -CH(L3)-0-, -0-L3-, -N-L3-, -S-L3-, -N(L3)-L5 - _L 3, L 4 and L 3 4 can be used individually Selected from the following group: C = 〇, C = S, 0 • 〇L3 OL3 N* -C——L5——, ^ and 〇l3 ; for the parent Li, L31, L2, L32, L4 and L 3 4, L 3 and L 5 may each independently be selected from the group consisting of: none, H, CH 2 C (= 0) 0 L 6 , substituted and unsubstituted hydrocarbyl groups, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted heterocycloalkyl groups, substituted and unsubstituted Substituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted alkoxy, t 228 201143772 substituted and unsubstituted hydrocarbonthio, And unsubstituted hydrocarbon amino groups, substituted and unsubstituted polyfluorohydrocarbon groups, and substituted and unsubstituted hydrocarbyl groups, wherein any carbon or hydrogen atom may be further further substituted by 0, S, P, NL3, or any other pharmaceutically acceptable Substituted by a accepting group; L6 may be independently selected from the group consisting of H, OH, Cl, F, Br, I, substituted and unsubstituted hydrocarbyl groups, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted heterocycloalkyl groups, substituted And _ unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted hydrocarbyloxy, substituted and unsubstituted hydrocarbylthio, substituted and unsubstituted hydrocarbylamino, substituted and unsubstituted polyfluoro a hydrocarbon group and a substituted or unsubstituted halogenated hydrocarbon group, wherein any carbon atom or hydrogen atom may be further further by 0, S, N, P(0)0L6, CH=CH, C3C, CHL6, CL6L7, aryl, hetero An aryl or a cyclic O group is substituted; L7 can be independently selected from the group consisting of H, OH, Cl, F, Br, I, substituted and unsubstituted hydrocarbyl groups, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted Heterocyclic hydrocarbon groups, substituted and unsubstituted aryl groups, substituted and unsubstituted heteroaryl groups, Substituted and unsubstituted alkoxy groups, substituted and unsubstituted hydrocarbonthio groups, substituted and unsubstituted hydrocarbon amino groups, substituted and unsubstituted polyfluorohydrocarbon groups, and substituted and unsubstituted halogenated hydrocarbon groups, any carbon atom or hydrogen Atomic separable|JL 229 201143772 further substituted by hydrazine, s, N, P(0)0L6, CH=CH, C tri C, CHL6, CL6L7, aryl, heteroaryl or cyclic group; and any CH2 The group can be replaced by hydrazine, S or NH. 10. The highly permeable composition according to claim 9 having a structure selected from the group consisting of structural formula P-1, structural formula P-2, structural formula P-3, structural formula P-4, Structural formula P-5, structural formula P-6, structural formula P-7, structural formula P-8, structural formula P-9, structural formula P-1, structural formula P-1, structural formula P-1 Structural formula P -1 3 , structural formula P -1 4 , structural formula P - 1 5 , structural formula P - 1 6 , structural formula P - 1 7 , structural formula P - 1 8 , structural formula P - 1 9, Structural formula P - 2 0, structural formula P - 2 1, structural formula P - 2 2, structural formula P - 2 3, structural formula P - 2 4, structural formula P - 2 5, structural formula P - 2 6, structure Formula P - 2 7, Structural Formula P - 2 8, Structural Formula P - 2 9, Structural Formula P - 3 0, Structural Formula P - 3 1, Structural Formula P - 3 2. Structural Formula P - 3 3. Structural Formula P - 3 4, structural formula P - 3 5, structural formula P - 3 6, structural formula P - 3 7, structural formula P - 3 8, structural formula P - 3 9, structural formula P - 4 0, structural formula P - 4 1. Structural formula P-42, structural formula P-43, structural formula P-44, structural formula P-45, structural formula P-46, structural formula P-47, structural formula P-4, structural formula P - 4 9 Structural formula P - 5 0, structural formula P - 5 1. Structural formula P - 5 2. Structural formula P - 5 3. Structural formula P - 5 4. Structural formula P-55, structural formula P-56, structural formula P-57, structure ί α 230 201143772 Formula P - 5 8. Structural formula P - 5 9. Structural formula P - 6 0, Structural formula Ρ - 6 Bu structure Ρ - 6 2. Structural formula Ρ - 6 3. Structure Ρ - 6 4. Structural formula P-65, structural formula P-66, structural formula P-67, structural formula P - 6 8. Structural formula P - 6 9. Structural formula P - 7 Ο, structural formula Ρ - 7 1. Structural formula 7 - 7 2. Structural formula Ρ - 7 3. Structural formula Ρ - 7 4. Structural formula Ρ - 7 5. Structural formula Ρ - 7 6. Structural formula Ρ - 7 7. Structural formula Ρ - 7 8 , Structural formula Ρ - 7 9. Structural formula Ρ - 8 0, Structural formula Ρ - 8 1. Structural formula Ρ - 8 2. Structural formula Ρ - 8 3. Structure • Formula Ρ - 8 4. Structural formula Ρ - 8 5 , Structural formula Ρ - 8 6. Structural formula I - 1, structural formula I - 2, structural formula I - 3, structural formula I - 4, structural formula 1-5, structural formula 1-6, structural formula 1-7, Structural Formula 1-8, Structural Formula I-9, Structural Formula I-1, Structural Formula I-1, Structural Formula I-1, Structural Formula I-1, Structural Formula I-1, Structural Formula I - 1 5, structural formula I -1 6. Structural formula I - 1 7. Structural formula I -1 8. Structural formula I - 1 9. Structural formula I - 2 0, structural formula I - 2 1. Structure I I - 2 2. Structural formula I - 2 3. Structural formula I - 2 4. Structural formula I - 2 5. Structural formula I - 2 6. Structural formula I - 2 7. Structural formula I - 2 8. Structural formula I - 2 9, structural formula I - 3 0, structural formula I - 3 1, structural formula I - 3 2, structural formula I - 3 3, structural formula S - 1, structural formula S - 2, structural formula S - 3, Structural formula S - 4, structural formula S - 5, structural formula S - 6, structural formula S - 7, structural formula S - 8, structural formula S - 9, structural formula S - 1 0, structural formula S - 1 1, Structural formula S - 1 2, structural formula S - 1 3, structural formula S - 1 4, structural formula S - 1 5, structural formula S - 1 6. Structural formula S -1 7. Structural formula S - 1 8. Structure Formula 231 201143772 S - 1 9. Structural formula S - 2 0, structural formula T-1, structural formula T-2, structural formula Τ-3, structural formula Τ-4, structural formula Τ-5, structural formula Τ- 6. Structural formula Τ-7, structural formula Τ-8, structural formula Τ-9, structural formula Τ-1 0, structural formula Τ-1, structural formula Τ-1, structural formula Τ-1, structural formula Τ - 14, structural Τ - 1 5, and the structure Τ - 1 6, Structural formula -1 Structure P-2 Structural formula P-5 [SI 232 201143772 Structural formula P-7 Structural formula P-8 Structural formula P-9 Structural formula P -1 0 Structural formula P -1 1 Structural formula P -1 2 Structural formula P -1 4 Construction P -1 3 233 201143772 Construction P -1 7 Structural Formula P -1 8 Structural formula P -1 9 Structural formula P - 2 0 234 201143772 Structural Formula P - 2 1 Structural Formula P - 2 2 Y' Structural formula P-23 Structural formula P-24 Structural formula P - 2 6 Structural formula P - 2 5 Rt 0~~*R〇 Ri ^ .N-CH? 〆 \ R, ch2 c /丫" Structure P-27 235 201143772 Structural formula P - 3 1 Structural formula P - 3 2 Structural formula P - 3 3 Structural formula P - 3 4 Structural formula P - 3 5 Structural formula P - 3 6 236 201143772 s, x5, -r7 nv O' ORe /s / \ i2 〇 'ORe 0-Re s, x6, Structural formula P - 3 7 Structural formula P - 3 8 Structural formula P - 4 1 Structural formula P-42 HA H?N \ OR, 0-Rs Structural P-43 Structural P-44 237 201143772 Structural P-45 Structural P-46 Structural formula P-47 Structural formula P-49 Structural formula P - 5 1 238 201143772 Structural formula P - 5 3 Structural formula P - 5 5 Structural formula P - 5 6 Structural formula P - 5 7 Structural formula P - 5 8 Structural formula P-59 Structural formula P-60 239 201143772 Structural formula P - 6 1 Structural formula P-62 Structural P-64 Structural P-64 Υ2 Η Λ Ο—Re Ν Structure Ρ-65 Structure Ρ 66 240 201 143772 Γ2 Η: X-W Structural P-67 Structural Formula P-68 _ Structural formula P-70 Structural formula P-69 ^1x5 Structural formula P - 7 1 241 201143772 P-74 Structural formula P-75 242 201143772 Structural formula P - 8 1 Structural formula P - 8 2 Structural P-83 Structural Formula P-84 243 201143772 Structural formula P-8 5 Structural formula P - 8 6 Structural formula 1-4 Structural formula 1-5 Structural Formula I - 8 Structural Formula I · 9 244 201143772 Structural Formula I -1 ο Structural Type ι -11 Configuration I - 1 4 Structural Formula I -1 5 Structural Formula I -1 6 Structural Formula I - 1 7 245 201143772 Structural Formula I - 1 9 Structural Formula I -1 8 Structural formula 1-23 Structural formula 1-22 Structure 1-25 Structure 1-24 Structural formula 1-26 246 201143772 Structural Formula I - 2 8 Structural Formula 1-29 Structural Formula I - 3 0 Structural Formula I - 3 1 w 247 201143772 Structural S-3 Structural S-4 Χβ Structural S-6 , Xs, Structure S-7 Structural S-8 Structural S - 9 Structural S - 1 0 s. j J 248 201143772 Structural formula S - 1 1 Structural formula S - 1 2 Structural formula S - 1 3 S- 1 6 Structural formula S _ 1 7 Structural formula S - 1 8 249 201143772 Structural S - 1 9 Structural S - 2 0 Structure type T-4 structure type 结构-5 structure type Τ-6 formula Structural type Τ-8 250 201143772 Structural formula T-9 Structural formula Τ-10 Structural formula τ-11 Structural formula -12 Structure Τ-13 Τ-16, including its stereoisomers and pharmaceutically acceptable salts thereof; wherein each of m and η may be independently selected from the group consisting of 0 and the integer structure 251 201143772, and R!-R2 may be independently selected from the group consisting of Lower group: anthracene, substituted and unsubstituted hydrocarbon groups, substituted and unsubstituted cyclic hydrocarbon groups, substituted and unsubstituted heterocyclic hydrocarbon groups, substituted and unsubstituted alkoxy groups, substituted and unsubstituted alkenyl groups, substituted and unsubstituted Alkynyl, substituted and unsubstituted aryl and substituted and unsubstituted heteroaryl; R5 is selected from the group consisting of hydrazine, -CONH2, CH2CH2OR6, • CH2CH2N(CH3)2, CH2CH2N(CH2CH3)2, C1, F , B r, I, substituted and unsubstituted hydrocarbyl groups, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted heterocycloalkyl groups, substituted and unsubstituted hydrocarbyloxy groups, substituted and unsubstituted cyclohydrocarbyloxy groups, substituted And unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted hydrocarbon carbonyl, substituted and unsubstituted hydrocarbon amino, • -COW, hH-W and W; R 5 and R 3 5 respectively Independently selected from the group consisting of Η, C(=0)NH2, CH2CH2OR6, CH2CH2N(CH3)2, CH2CH2N (CH2C H3)2, Cl, F, Br, I, substituted and unsubstituted hydrocarbyl groups, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted heterocycloalkyl groups, substituted and unsubstituted hydrocarbyloxy groups, substituted and unsubstituted Cycloalkoxy, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and not 252 hydrocarbon hydrocarbon carbonyl, substituted and unsubstituted hydrocarbon amino group, -C(=0)-W ' L1-L4-L2-W W ; R6, R36 and R46 can be independently selected from the group consisting of Η, F, Cl, Br, I, Na+, K+, C(=0)R5, 2-oxo-1 - 2-oxo-l-imidazolidinyl, phenyl, 5-indanyl, 2,3-dihydro-*~~rat-in-5 (2,3-dihydro-lH-inden-5-yl), 4-hydroxy-1,5-naphthyridin-3-yl, 4-hydroxy-l, 5-naphthyridin-3-yl And unsubstituted hydrocarbyl groups, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted heterocycloalkyl groups, substituted and unsubstituted alkenyl groups, substituted and unsubstituted alkynyl groups, substituted and unsubstituted alkoxy groups, substituted and Unsubstituted cycloalkyloxy, substituted and unsubstituted aryl, substituted and unsubstituted Base, -C(=0)-W, IM-L4-L2-W and W; R7 may be selected from the group consisting of H, F, Cl, Br, I, CH3NHC(=0)CH2CH(NHR8)C( = 0), r5n = c(nhr6)nhc( = o)-, c( = o)ch3, c( = o)r6, po(or5)or6, substituted and unsubstituted hydrocarbyl, substituted and unsubstituted cycloalkyl , substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted alkoxy, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted LJ 253 201143772 Heteroaryl, substituted and unsubstituted hydrocarbon carbonyl, substituted and unsubstituted hydrocarbon amino, LM-L4-L2-W and C(=0)-W; R8 and R38 may each independently be selected from the group consisting of Η: , F, Cl, Br, I, CH3, C2H5, CF3, CH2CH2F, CH2CH2C1, CH2CH2Br, CH2CH2I, CH2CHF2, CH2CF3, CH2F-CH2CM, CH2Br, CH2I, CH2NR6R7, • ch(nhr7)ch2c(=o)nh2, C3H7 , C4H9, C5Hh, r6, c( = o)r6, c( = o)nh2, ch2c( = o)nh2, ch2oc( = o)nh2, PO(OR5)OR6, c(ch3)2c( = o) Or6, ch(ch3)c( = o)or6, ch2c(=o)or6, C(=0)-W, and W, substituted and unsubstituted hydrocarbyl, substituted and Unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted polyfluorohydrocarbyl, substituted and unsubstituted hydrocarbyloxy, substituted and unsubstituted hydrocarbylamino, substituted and unsubstituted polyfluorohydrocarbyl , substituted and unsubstituted ii-hydrocarbyl and substituted and unsubstituted hydrocarbon carbonyl; W is selected from the group consisting of hydrazine, substituted and unsubstituted hydrocarbyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, Substituted and unsubstituted alkoxy groups, substituted and unsubstituted alkenyl groups, substituted and unsubstituted alkynyl groups, A 254 201143772 and unsubstituted aryl groups, substituted and unsubstituted heteroaryl groups, structural formula Wa, structures Formula W-1, structural formula W-2, structural formula W-3, structural formula W-4, structural formula W-5, structural formula W-6, structural formula W-7, structural formula W-8, structural formula W - 9, structural formula W-1 0, structural formula W-1 1, structural formula W-12, structural formula W-13, structural formula W-14, structural formula W-1, structural formula W-1, structure W- 1 7 and structural W- 1 8, Structural Wa, Structural W-1, Structural W-2, Structural formula W-3 Structure W-4 Structure W-5 Structure W-6 255 201143772 Structure W-7 Structure W-8 Structure W-9 Structure W-10 Structure W-11 Structure HA Structural formula w-13 Structural formula W-14 Structural formula W- 1 5 256 201143772 Structure W- 1 6 Structure W- 1 7 Structure W- 1 8. X is selected from the group consisting of: none, C (= 0), 0C (= 0), CH2, CH, S, NH, NR6, and Ο; X2 is selected from the group consisting of: none, hydrazine, CH2(CH2)nOR8, Cl, F, Br, I, N02, CN, CF3, C2F5, C3F7, OCF3, OC2F5, NH2, NHR6, CH3, C2H5, R6, c ( = o) nh2, CH20C (= 0) NH2, CH2C (= 0) OR5, CH2(CH2)nN(CH3)2, CH2(CH2)nS03R5, substituted and unsubstituted polyfluorohydrocarbyl, substituted and unsubstituted hydrocarbyl , substituted and unsubstituted hydrocarbonthio, substituted and unsubstituted hydrocarbon amino, and substituted and unsubstituted alkoxy; X4 is selected from the group consisting of: N, CH, and CYi; X5 and X35 are each independently selected from the group consisting of · none, c(=o), 0C(=0), CH2, CH, S, 0, and NR5; X6, X36, and X46 can be independently selected from the group consisting of: none, C, and 0) , 0C ( = 0), CH2, CH, S, 0, and NR5; X 7 can be independently selected from the following groups: none, c (= O), 0C (= 0), CH2, CH, S, ο, and Nr5; r 257 201143772 Υι, Y31, Υ2, Υ32, Υ3 and Υ4 are each independently selected from the group consisting of H, OH, OW, 0C (= 0) W, LM-L4-L2-W, 0C (= 0) CH3 , CH3, C2H5, C3H7, C4H9, R6, S03R6, CH2OR6, ch2oc(=o)r6, CH2C(=0)0R8, OCH3, OC2H5, OR6, ch3so2, r6so2, ch3so3, r6so3 , N02, CN, CF3, OCF3, CH2(CH2)nNR5R6, CH2(CH2)n〇R6 CH(C( = 0)NH2)NHR6, • CH2C( = 0)NH2, F, Br, I, Cl, ch = chc( = o)nhch2c( = o)ow, CH-CHC( = 0)NHCH2L1-L4-L2-W ' NR8C( = 0)R5, S02NR5R8, C( = 0)R5, SR5, substituted and unsubstituted Polyfluoroalkyl, substituted and unsubstituted alkoxy, substituted and unsubstituted hydrocarbonthio, substituted and unsubstituted hydrocarbon amino, substituted and unsubstituted polyfluoroalkyl, substituted and unsubstituted halogenated hydrocarbon and Substituted and unsubstituted hydrocarbon carbonyl; Z is selected from the group consisting of CH2, S, SO, S02, NH, NR6, CHCH3, CHCH2CH3, CR6, R6, -c(=o) and o; AA stands for any amino acid; From the following groups: no, hydrochloric acid, hydrogen acid, hydrogen moth acid, nitric acid, sulfuric acid, sulfurous acid, phosphonic acid, sub-acid, acid, isonicotinic acid, acetic acid, lactic acid, salicylic acid, lemon t 258 201143772 acid , tartaric acid, pantothenic acid, acid tartaric acid, ascorbic acid, succinic acid, maleic acid, gentian acid, fumaric acid, gluconic acid, glucaronic acid, sugar acid, formic acid, benzoic acid, Acid, formazanic acid, phthalic acid, benzenesulfonic acid, p-benzoic acid and pamoic acid; R is selected from the group consisting of: no, hydrazine, CH2C (= 0) 0R6, substituted and unsubstituted hydrocarbyl groups , substituted and unsubstituted cycloalkyl, #substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted hydrocarbyloxy, substituted and unsubstituted polyfluorohydrocarbyl, substituted and unsubstituted il hydrocarbyl, substituted and unsubstituted Alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl and substituted and unsubstituted heteroaryl, wherein any CH2 in R can be pharmaceutically acceptable by hydrazine, S, P, NR6 or any other Substituting a group; # Rs and Y together are R6〇CH2C(R5)=, or are themselves selected from the group consisting of: R600CCH(NHR7)(CH2)nC(=0)NH-, R6OOCCH(NHR7)(CH2) nSC( = 0)NH-, CF3SCH2C( = 0)NH-, CF3CH2C( = 0)NH-, 259 201143772 chf2sch2c( = o)nh-, ch2fsch2c( = o)nh-, nh2c( = o)chfs-ch2c ( = o)nh-, r7nhch(c( = o)ow)ch2sch2c( = o)nh-, R7NHCH(L1-L4-L2-W)CH2SCH2C( = 0)NH- 'CNCH2SCH2C( = 0)NH-, CH3(CH2)nC( = 0)NH-, R7N = CHNR7CH2CH2S-, R7N = C(NHR7)NHC( = 0)- ' R7n = c(nhr7)nhc( = o)ch2, CH3C(C1) = CHCH2SCH2C( = 0)NH-, (CH3)2C(OR6)-, CNCH2C( = 0)NH-, CNCH2CH2S-, R7HN = CH( NR7)CH2CH2S-, ch2 = chch2sch2c( = o)nh-, CH3CH(OH)-, 260 201143772 CH3CH(OR8)- 'CH3CH(Y,)- ' (CH3)2CH- 'CH3CH2-, CH3(CH2)nCH = CH(CH2)mC 卜0)NH-, where n or m is a rational number greater than 0, structural formula Rs-1, structural formula Rs-2, structural formula Rs-3, structural formula Rs-4, structural formula R s - 5, structural formula R s - 6, structural formula R s - 7, structural formula R s - 8, structural formula Rs-9, structural formula Rs-10, structural formula Rs-1, structural formula Rs-12, structure Formula Rs-13, structural formula Rs-14, structural formula Rs-1, structural formula Rs-1, structural formula Rs-1, structural formula R s - 1 8, structural formula R s - 1 9, structural formula R s - 2 0, structural formula Rs-2 1, structural formula Rs-22, structural formula Rs-23, structural formula Rs-24, structural formula Rs-25, structural formula Rs-26, structural formula R s - 2 7 , structural formula R s - 2 8 , structural formula R s - 2 9, structural formula rri L a J 261 201143772 R s - 3 0, structural formula R s - 3 1, structural formula R s - 3 2, structural formula Rs -33, structural formula Rs-34, structural formula Rs-3 5. Structural formula R s - 3 6. Structural formula R s - 3 7. Structural formula R s - 3 8. Structural formula R s - 3 9. Structural formula R s - 4 0, structural formula R s - 4 1. Structural formula Rs-42, structural formula Rs-43, structural formula Rs-44, structural formula Rs-45 and structural formula Rs-46, 262 201143772 Structural Formula Rs-3 Structural Formula Rs-4 Structural formula Rs-5 Structural formula Rs-6 263 201143772 Structural formula Rs-9, Structural formula R s - 1 0 Formula Rs-1 1 Structural Formula R s - 1 2 CONH- h2 R7 ′ structure Rs-13 OCHO Yi Structure R s - 1 4 OR7 Yi CONH CONH structure R s -1 5 Structural formula R s - 1 6 264 201143772 Structural formula Rs-1 8 Υι CONH NHRy H2 Structural formula Rs-21 Structural formula R s - 2 0 ^-CONH Structural Formula Rs-2 2 265 201143772 Style Rs-2 3 Structural Formula Rs-24 Structural formula R s - 2 5 Structural formula R s - 2 6 266 201143772 Type R s - 2 9 Structure R s - 3 0 Formula Rs-31 r^^r^N, CONH——COOW Structure Structure Rs-32 Rs-33 structural formula Rs-34 Rs-35 structural formula R s - 3 6 267 201143772 COOH Rs-37 Structure Rs-38 Y1 V1 Formula R s - 3 9 Structural Formula R s - 4 0 268 201143772 Structural formula Rs-43 Structural formula Rs-44 The structural formula Rs-45 has the structural formula Rs-46; R!b 16 is independently selected from the group consisting of: none, hydrazine, CI^COOR! i, substituted and unsubstituted hydrocarbon groups, substituted and unsubstituted cyclic hydrocarbon groups, substituted and unsubstituted Substituted heterocycloalkyl, substituted and unsubstituted hydrocarbyloxy, substituted and unsubstituted polyfluorohydrocarbyl, substituted and unsubstituted functional hydrocarbyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted And unsubstituted aryl and substituted and unsubstituted heteroaryl; 269 201143772 L1 and L 3! can be independently selected from the group consisting of: none, Ο, S, -Ο - L 3 ' -S-L3-, -N(L3)-, -N(L3)-CH2_〇, -n(l3)-ch2-n(l5)-, -o-ch2-〇-, -o-ch(l3)-o and - S-ch(l3)-o-; L2 and L32 can be individually selected from the group consisting of: none, o, s, -0-L3-'-S-L3-, -N(L3)-, -N( L3)-CH2-0, -N(L3)-CH2-N(L5)-, -0-CH2-0-, -0-CH(L3)-0, -S-CH(L3)-0-, -0-L3-, -N-L3-, -SL]-, -N(L3)-L5- and L3, L4 and L34 may each independently be selected from the group consisting of c = o, c = s, NT 01-3 /〇l3 N 〇p 〇l5 C L5 ^ C and ol3 ; for each L!, L3 1, L 2, L 3 2 , L4 and L 34. L3 and L5 may each independently be selected from the group consisting of: none, hydrazine, CH 2 C (= Ο) OL 6, substituted and unsubstituted hydrocarbon groups, substituted and unsubstituted cyclic hydrocarbon groups, substituted and unsubstituted heterocyclic hydrocarbon groups. , substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted hydrocarbyloxy, substituted and unsubstituted hydrocarbylthio, substituted and unsubstituted hydrocarbylamino, substituted and unsubstituted a fluorohydrocarbyl group and a substituted or unsubstituted halohydrocarbyl group, wherein any carbon or hydrogen atom may be further substituted with 0, S, P, NL3, or any other pharmaceutically acceptable group, respectively; 270 201143772 L6 may be independently selected from the group consisting of :H, OH, Cl, F, Br' I, substituted and unsubstituted hydrocarbyl groups, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted heterocycloalkyl groups, substituted and unsubstituted aryl groups, substituted and unsubstituted Heteroaryl, substituted and unsubstituted alkoxy groups, substituted and unsubstituted hydrocarbonthio groups, substituted and unsubstituted hydrocarbon amino groups, substituted and unsubstituted polyfluorohydrocarbon groups, and substituted and unsubstituted halogenated hydrocarbon groups, any of which Carbon or hydrogen atoms can be separately The step is substituted by 0, S, N, P(0)OL6, CH=CH, CeC, chl6, cl6l7, aryl, heteroaryl or cyclic group; L7 can be independently selected from the group consisting of H, OH, Cl , F, Br, I, substituted and unsubstituted hydrocarbyl groups, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted heterocycloalkyl groups, substituted and unsubstituted aryl groups, substituted and unsubstituted heteroaryl groups, substituted and Unsubstituted alkoxy groups, substituted and unsubstituted hydrocarbonthio groups, substituted and unsubstituted hydrocarbon amino groups, substituted and unsubstituted polyfluorohydrocarbon groups, and substituted and unsubstituted halogenated hydrocarbon groups, wherein any carbon or hydrogen atom may be used. Further substituted by hydrazine, s, N, P(0)0L6, CH=CH, CeC, chl6, cl6l7, aryl, heteroaryl or cyclic groups; and any CH2 group may be deuterium, S or NH Replace. 271 201143772 11. A pharmaceutical composition comprising a composition of the ninth to permeable form of the patent application and a pharmaceutically acceptable carrier. The pharmaceutical composition of the above-mentioned patent scope U is a pharmaceutically acceptable carrier which is polar. 13. If the pharmaceutical composition described in the application of U.S. The acceptable carrier for use is selected from the group consisting of: alcohol, bismuth, vinegar, water, and aqueous solution: 14 specific: a method of permeating the barrier: including administering the drug as described in claim 11 to the biological barrier. combination. A method for transposing hpp of an antibacterial agent or an antibacterial agent-related compound, comprising the steps of: U covalently attaching a functional unit containing an antibacterial agent or an antimicrobial-related compound to a transport unit forming composition by a linker 2) The test composition is administered to a biological system or biological month 3) to determine if the test composition has the desired properties or characteristics. 16. The method of claim 15, wherein the quality is selected from the group consisting of: / 1) the ability of the test composition to penetrate the biological barrier, 2) the test composition is converted to a parent drug or active agent Ability; 3) penetration rate of the test composition; 272 201143772 4) efficiency of the test composition; and 5) effect of the test composition. 17. The use of the scope of application of the patent application, comprising the steps of: administering the composition of the nine items to any of the compositions described in the screening organisms; 1) claiming the ninth organism; 2) detecting the presence, location or amount of the composition and the substance in the organism to detect the symptoms caused by the composition. The method of item 17, wherein the composition 18. is marked with a mark as claimed in the patent application. 19. The use of the composition of claim U in the screening of organisms comprises the following steps: 1) administering any of the compositions described in claim U to an organism; Detecting the presence, location or amount of the composition in the organism; and 3) the symptoms elicited by the composition detected in the organism. 20. The method of claim 19, wherein the composition is labeled. [S] 273 201143772 21. Use of a composition for the treatment of a symptom using a composition of claim 9 wherein the symptom comprises pain, injury, or symptoms associated with a microorganism. 22. Use of an antibacterial agent for treating a condition using a composition of the scope of the application of the scope of the invention, wherein the symptom is selected from the group consisting of pain, injury and microbiological related symptoms. 23. The method of claim 21, wherein the microbial-related symptoms are selected from the group consisting of bacterial-related symptoms, protozoa-related symptoms, and fungal-related symptoms and symptoms caused by the virus. The method of claim 23, wherein the bacterial-related symptoms are selected from the group consisting of infection, plague, bubonic plague and pneumonic plague, anthrax anthrax, pulmonary anthrax and gastrointestinal charcoal, Lyme disease, Brucellosis, pertussis, acute enteritis, respiratory infection, crane crane fever, non-gonococcal shoulder inflammation, trachoma, neonatal inclusion body conjunctivitis, sexually transmitted lymphogranuloma, pseudomembranous colitis, gas septic disease, food poisoning Anaerobic fungus bee: two diseases, neonatal meningitis, hemorrhagic colitis, red syndrome of lytic urinary tract, rabbit fever, pneumonia 'branched gas field= disease:: Tiac heat, hook end Helicobacter pylori, Lee's rod two two =:,: _, mycoplasma pneumonia, gonorrhea, neonatal eyelids owe, epidemic meningitis, Hua Fu's comprehensive 274 201143772 meningococcal bacteremia), Luo Rocky mountain spotted fever, typhoid fever type salm〇neu〇sis, salmonellosis with gastroenteritis and colitis, bacterial disease/bacteriosis, cystitis, meningitis and septicemia, Endometritis, middle , Sinusitis, syphilis, necrotizing fasciitis, streptococcal pharyngitis, m red hot, hot wind ^, impetigo, erysipelas, puerperal fever and cholera. 25. The method of claim 24, wherein the infection symptom is selected from an infection of an organ of the lower group: liver, lung, stomach 'brain, kidney, dirty ear, nose, mouth, tongue, Colon, pancreas, gallbladder, + two-neck, rectum stomach, colorectal, intestine, vein, respiratory system, vascular, anorectal and anal pain, respiratory infection, upper respiratory tract, urinary tract Infection, nosocomial infection, pseudomonas infection, : solid enzyme-positive staphylococcal infection, skin infection, poisoning, acute endocarditis, septicemia, necrotizing pneumonia, post-prosthetic infection, accompanied by septicemia Opportunistic infections of illness and pneumonia. The method of claim 23, wherein the protozoan-related symptoms are selected from the group consisting of a disease, a sleeping sickness, and a toxoplasmosis. The method described in claim 23, wherein the fungal related disease = from the following group: Aspergillosis, blastomycosis, sputum bacillus, candidiasis, disease, cryptococcosis, histobacterial disease, Brazilian bud disease , Yezi,,, 糸 病 接合 and zygomycosis. The method of claim 23, wherein the virus-related symptoms are selected from the group consisting of influenza, yellow fever, and AIDS. [S] 276