WO2005058875A1 - Composes de piperazine triazine, leur obtention, et preparations pharmaceutiques les contenant - Google Patents

Composes de piperazine triazine, leur obtention, et preparations pharmaceutiques les contenant Download PDF

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Publication number
WO2005058875A1
WO2005058875A1 PCT/CN2004/001368 CN2004001368W WO2005058875A1 WO 2005058875 A1 WO2005058875 A1 WO 2005058875A1 CN 2004001368 W CN2004001368 W CN 2004001368W WO 2005058875 A1 WO2005058875 A1 WO 2005058875A1
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aryl
fluorenyl
formula
hydrogen
substituted aryl
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PCT/CN2004/001368
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English (en)
Chinese (zh)
Inventor
Hualiang Jiang
Hong Liu
Xu Shen
Xingzu Zu
Mingyue Zheng
Mingfang Zheng
Xinquan Ji
Haibin Luo
Hongxia Guo
Xiaomin Luo
Jianhua Shen
Kaixian Chen
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Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences
Shanghai Leaddiscovery Pharmaceutical Company
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Publication of WO2005058875A1 publication Critical patent/WO2005058875A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
    • C07D251/40—Nitrogen atoms
    • C07D251/54—Three nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to the fields of medicinal chemistry and medicinal therapy, and particularly to piperazine triamidine compounds, a preparation method thereof, and a pharmaceutical composition containing such compounds.
  • inflammatory mediators such as rheumatoid arthritis, rheumatic fever, osteoarthritis
  • asthma chronic obstructive pulmonary disease
  • trauma trauma, burns, endotoxin shock
  • Alzheimer's disease and even heart failure are involved in inflammatory mediators.
  • a single mediator is not the entire cause of the pathophysiology of inflammatory disorders.
  • AA arachidonic acid
  • PGs prostaglandin
  • LTs leukotriene
  • C0X Cyclooxygenase
  • PGs prostaglandin
  • LTs leukotriene
  • the metabolism of AA has the following two pathways: (1) Cyclooxygenase (C0X) metabolic pathway, that is, AA is metabolized into PGs through a series of reactions under the catalysis of C0X; (2) Lipoxygenase (5-L0X) metabolism Pathway, that is, AA is metabolized into LTs under the catalysis of 5-LOX. Therefore, blocking the metabolism of M can inhibit the production of inflammatory mediators PGs and LTs, thereby achieving the purpose of treating or weakening inflammation.
  • C0X Cyclooxygenase
  • 5-LOX lipoxygenase
  • the first metabolic pathway includes the following series of reactions: Membrane phospholipids produce free arachidonic acid (AA) via ttl phospholipase A 2 (PLA 2 ), and AA via cyclooxygenases (COX-1 and COX-2) The effect is converted into prostaglandin G 2 (PG 2 ), and its peroxidase activity then converts its product to prostaglandin H 2 (PGH 2 ). Tissue-specific isoenzymes metabolize PGH 2 into other forms of prostaglandins Or thromboxane A 2 (TxA 2 ). At the same time, AA is metabolized to leukotrienes (LTs) by 5-lipoxygenase.
  • LTs leukotrienes
  • glucocorticoid anti-inflammatory drugs SAID
  • NSAID non-body anti-inflammatory drug
  • COX-1 is expressed in normal tissues and is a constituent protein of normal cells
  • COX-2 is an induced form of enzymes, mainly in inflammatory cells, such as endothelial cells, macrophages, synovial fibroblasts, It is expressed in dendritic cells, chondrocytes and osteoblasts, and has similar active binding sites to COX-1 to AA or NSAID
  • COX-2 can be induced by various factors in inflammatory tissues, and its level will be 8-10 The rate increased sharply, causing the contents of PGE 2 , PGI 2 and PGE in the inflammation site to increase, which promoted the inflammatory response and tissue damage.
  • Classic NSAIDs such as aspirin, indomethacin, and diclofenac are selective inhibitors of COX and generally do not affect 5-LOX metabolism. They not only affect the synthesis of PGs that have protective effects on the gastric mucosa, but also because A single inhibition of COX-2 resulted in increased LOX metabolic activity, caused an AA metabolic imbalance, promoted an increase in the synthesis of LTs substances, thereby promoting the chemotactic aggregation of white blood cells and increasing vascular permeability. Therefore, Dr. Vane proposed: A full-functioning anti-inflammatory drug with low toxicity and side effects, which should simultaneously inhibit COX and 5-LOX. In fact, the research on dual COX-2 / 5-LOX inhibitors has been the focus of research on anti-inflammatory drugs by medical workers at home and abroad in recent years.
  • Computer-Aided Drug Design has become an important method and tool for modern drug research and development.
  • Computer-assisted drug design especially computer-assisted combinatorial chemical library design, has been incorporated into new drug research. Recycling can shorten the cycle of new drug research, save research and development costs, and improve the hit rate of new drug screening.
  • the combination of computer-aided drug design and other modern drug research methods will promote the rapid development of disciplines related to pharmacy and life sciences.
  • the CADD method has been widely used in the discovery and optimization of lead compounds, and some large international pharmaceutical companies have given full attention to the application of this technology in the research of new drugs.
  • Structural biology has also entered the applied research phase from the original basic research.
  • One of the main application fields is to study the interaction between drugs and target proteins at the molecular and atomic structure level, and to determine the crystal structure of drug-protein complexes.
  • the design of new compounds and the structural modification of lead compounds provide useful structural information.
  • research in this area has progressed rapidly, and structural biology techniques and methods have been successfully applied in the research of anti-AIDS drugs, anti-cold virus drugs and anti-cancer drugs.
  • Human genome sequencing has been completed and combined with bioinformatics, structural biology will play an important role in the discovery of new targets for drug action.
  • the inventors comprehensively used the three-dimensional structures of COX-1, COX-2 and 5-LOX (including COX-1 and COX-2 as crystal structures, and the three-dimensional structure of 5-L0X using homologous protein modeling method).
  • Computer-assisted drug molecular design, combinatorial chemistry, molecular biology, and structural biology methods to find lead compounds with dual inhibitors of COX-2 / 5-LOX and optimize their structure for their pharmacological effects.
  • the inventors have found piperazine-triazine compounds having a new structure for a good combination C0X-2 enzymes, the dissociation constant of 10-6 and mouse carrageenan paw edema model has a good anti-inflammatory effect, thus completing the this invention. Summary of the invention
  • An object of the present invention is to provide a piperazinetriazine compound having a dual inhibitory effect on COX-2 / 5-LOX.
  • Another object of the present invention is to provide a method for synthesizing piperazine triazine compounds by using trichloromethane as a raw material.
  • Another object of the present invention is to provide a pharmaceutical composition for treating inflammatory diseases containing a piperazinetriazine compound.
  • the present invention provides a piperazine triazine compound or a pharmaceutically acceptable salt thereof having the structure of the following general formula (I):
  • R is H, dC 4 fluorenyl, aryl, substituted aryl, arylfluorenyl, alkanoyl, aroyl, or C 3 -C 7 cyclofluorenyl;
  • X is NR 7 , 0 or S
  • R 3 is aryl, substituted aryl, arylfluorenyl, fluorenylaryl or C 3 -C 7 cycloalkyl;
  • R4 is hydroxy or ⁇ - ⁇ fluorenyl
  • R 6 is hydroxyl or -fluorenyl
  • R 7 is hydrogen, hydroxy or fluorenyl
  • R 8 is hydrogen, hydroxy, aryl, heteroaryl ring, heterocyclyl or C2-C6 alkenyl hydrocarbon.
  • compositions include propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, and the like.
  • inorganic bases such as sodium, potassium, calcium, aluminum salts, and phosphonium salts
  • organic bases such as methylamine salts , Ethylamine salts, ethanolamine salts, etc.
  • a preferred embodiment of the compound of formula (I) of the present invention is the following piperazinetriazine compound or a pharmaceutically acceptable salt thereof:
  • Ri is H, d-Ct alkyl, aryl, substituted aryl, aralkyl, d-alkanoyl, aroyl or C 3 -C 7 cyclofluorenyl;
  • R4 is hydroxy or ⁇ - ⁇ fluorenyl
  • R 6 is hydroxy or- ⁇ alkyl
  • Another preferred embodiment of the compound of formula (I) of the present invention is the following piperazine triazine compound or a pharmaceutically acceptable salt thereof: '
  • H d-fluorenyl, aryl, substituted aryl, arylfluorenyl, d-fluorenyl, aroyl, or C 3 -C 7 cycloalkyl;
  • R 2 is aryl, substituted aryl, aralkyl, C, -C 4 alkylaryl or C 3 -C 7 cyclofluorenyl;
  • RA is hydroxy or ⁇ - ⁇ alkyl
  • R 6 is hydroxy or ⁇ - ⁇ -
  • R 8 is hydrogen, hydroxy, aryl, heteroaryl ring, heterocyclyl or C2-C6 alkenyl hydrocarbon.
  • Yet another preferred embodiment of the compound of formula (I) of the present invention is the following piperazinetriazine compound or a pharmaceutically acceptable salt thereof:
  • H -C4 alkyl, aryl, substituted aryl, arylfluorenyl, fluorenyl, aroyl, or C 3 -C 7 cycloalkyl;
  • R 2 is aryl, substituted aryl, arylfluorenyl, C r C 4 alkylaryl, or C 3 -C 7 cyclofluorenyl;
  • 3 ⁇ 4 is an aryl group, a substituted aryl group, an arylfluorenyl group, a CC 4 fluorenyl group, or a C 3 -C 7 cyclofluorenyl group;
  • R 6 is hydroxy or CC 6 alkyl
  • Yet another preferred embodiment of the compound of formula (I) of the present invention is the following piperazinetriazine compound or a pharmaceutically acceptable salt thereof:
  • R is H, C fluorenyl, aryl, substituted aryl, aralkyl, -fluorenyl, aroyl or 3 ⁇ 4-. 7 Huanyuanji; R 2 is aryl, substituted aryl, arylfluorenyl, -alkaryl or C 3 -C 7 cyclofluorenyl;
  • RA is hydroxyl or 6 -fluorenyl
  • R 6 is hydroxy or-. 6 ⁇ ⁇ ;
  • R 8 is hydrogen, hydroxy, aryl, heteroaryl ring, heterocyclyl or C2-C6 alkenyl hydrocarbon.
  • Another preferred embodiment of the compound of formula (I) of the present invention is the following piperazinetriazine compound or a pharmaceutically acceptable salt thereof:
  • R is H, d- embankment group, an aryl group, a substituted aryl group, an aryl group embankment, dC 4 embankment acyl, aroyl, or C 3 -C 7 cycloalkyl group homes;
  • R 3 is aryl, substituted aryl, arylfluorenyl, C-alkaryl or C 3 -C 7 cyclofluorenyl;
  • F is hydroxy or 6 alkyl
  • R 6 is hydroxy or -3 ⁇ 4 ⁇
  • R 8 is hydrogen, hydroxy, aryl, heteroaryl ring, heterocyclyl or C2-C6 alkenyl hydrocarbon.
  • the present invention also provides a triazine compound represented by the following formula (II), wherein the compound of the formula (II) is an intermediate for preparing the compound of the formula (I).
  • R is fluorenyl, aryl, substituted aryl, arylfluorenyl, fluorenyl, aroyl or ⁇ -. 7 cycloalkyl;
  • R 2 is aryl, substituted aryl, arylfluorenyl, CrC 4 fluorenyl or C 3 -C 7 cycloalkyl;
  • X is NR 7 , 0, S;
  • R 3 is aryl, substituted aryl, arylfluorenyl, fluorenyl or C 3 -C 7 cyclofluorenyl;
  • Y is hydrogen, halogen or -C4 amide
  • the present invention also provides a triazine compound represented by the following formula (III), wherein the compound of the formula (III) is an intermediate for preparing the compound of the formula (I).
  • R is 11, Ci-C 4 fluorenyl, aryl, substituted aryl, aralkyl, Cr C 4 acyl, aroyl or C 3 -C 7 cycloalkyl;
  • 2 is aryl, substituted aryl, arylfluorenyl, -alkaryl or C 3 -C 7 cyclofluorenyl;
  • Y is hydrogen, halogen, amino Cr fluorenyl
  • Z is hydrogen, halogen, amino C, -C 4 fluorenyl;
  • the present invention provides the following preparation method of a piperazine triazine compound represented by formula (I) or a pharmaceutically acceptable salt thereof:
  • R is H, fluorenyl, aryl, substituted aryl, aralkyl, -fluorenyl, aroyl or C 3 -C 7 cyclofluorenyl;
  • R 2 is aryl, substituted aryl, arylfluorenyl, dC 4 alkylaryl or C 3 -C 7 cyclofluorenyl;
  • X is NR 7 , 0 or S
  • 3 ⁇ 4 is an aryl group, a substituted aryl group, an arylfluorenyl group, a cc 4 fluorenyl group, or a c 3 -c 7 cyclofluorenyl group;
  • F is hydroxyl or 6 -fluorenyl
  • R 7 is hydrogen, hydroxy or CrQs alkyl
  • the method mainly includes the following steps: (1) Combining the formula (IV)
  • the reaction described in step (1) is usually carried out in an inert solvent at 20-100 ° C.
  • the solvent used may be THF, Et 2 0, DMF, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, dioxane and the like.
  • the base used is selected from organic bases including pyridine, triethylamine, 4-dimethylaminopyridine (DMAP), diisopropylethylamine, and inorganic bases including sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide .
  • the reaction described in step (2) is also performed in an inert solvent at 20-10 CTC.
  • the solvent used may be THF, Et 2 0, DMF, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, dioxane and the like.
  • the base used is selected from organic bases including pyridine, triethylamine, 4-dimethylaminopyridine (DMAP), diisopropylethylamine, and inorganic bases including sodium carbonate: potassium carbonate, sodium hydroxide, potassium hydroxide .
  • the polar organic solvent used in step (3) is selected from the group consisting of ethanol, methanol, ethyl acetate and tetrahydrofuran
  • the base used is selected from the group consisting of pyridine, triethylamine, 4-dimethylaminopyridine (DMAP), and diisopropyl
  • Organic bases of ethylamine and inorganic bases including sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide.
  • the products obtained in steps (1), (2), and (3) can be purified by appropriate methods such as column chromatography and recrystallization, respectively, to obtain pure products.
  • Another aspect of the present invention relates to a pharmaceutical composition for preventing and / or treating an inflammatory disease, the pharmaceutical composition comprising a piperazine triazine compound represented by formula (I) or a pharmaceutically acceptable salt thereof and at least one pharmacy It is an acceptable carrier which can be used for in vivo treatment and is biocompatible.
  • the pharmaceutical composition can be prepared into various forms according to different routes of administration.
  • the pharmaceutical composition of the present invention can be used for preventing and / or treating inflammatory diseases.
  • the pharmaceutical composition according to the present invention which can be used for preventing and / or treating inflammatory diseases refers to an effective dose of the compound of the formula I of the present invention or a pharmaceutically acceptable salt or hydrate thereof and one or more suitable pharmacological With carrier.
  • This pharmaceutical carrier includes, but is not limited to: ion exchangers, alumina, aluminum stearate, lecithin, serum proteins such as human albumin, buffer substances such as phosphate, glycerol, sorbic acid, potassium sorbate Partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyethylene Pyrrolidone, cellulose material, polyethylene glycol, sodium carboxymethyl cellulose, polyacrylate, beeswax, lanolin.
  • composition of the compound of the present invention can be administered in any of the following ways: oral, spray inhalation, rectal, nasal, buccal, topical, parenteral, such as subcutaneous, intravenous, intramuscular, intraperitoneal, intrathecal , Intraventricular, intrasternal, and intracranial injections or infusions, or with the aid of an explanted reservoir.
  • oral or intramuscular injection, intraperitoneal or intravenous administration are preferred when treating inflammation.
  • the dosage and method of use of the compounds of the present invention depend on many factors, including the age, weight, sex, natural health, nutritional status, intensity of the compound's activity, time of administration, metabolic rate, severity of the condition, and Subjective judgment of the treating physician. If the recommended dose is 5mg ⁇ 10mg / kg daily, the maintenance amount can be reduced to 3mg / kg per R. Capsule: 0.25g / capsule. Injection 0.25g / 5ml. Oral solution: 5g / 50ml. BRIEF DESCRIPTION OF THE DRAWINGS
  • Figure 1 shows the binding kinetics of piperazine triazines and cyclooxygenases (COX-1 and COX-2).
  • the instrument used was BIACORE3000, and the analysis software was Kinetic Analysis in the Application Wizard.
  • the cyclooxygenase 2 protein was fixed on the CM5 chip.
  • the concentration of piperazine triazine compounds tested was: 0.625, 1.25, 2.5, 5.0, and 10.0. ⁇ M.
  • UV lamp ( ⁇ : 254 ⁇ ) develops color; use 100 mesh to 200 mesh for column chromatography.
  • Column chromatography silica gel (produced by Qingdao Ocean Chemical Plant).
  • the prepared 0.525 g of crude product was dissolved in an appropriate amount of methanol to obtain a clear solution; it was slowly dropped into a large excess of piperazine hexahydrate in a methanol solution, stirred at room temperature for 0.5 hours, and then refluxed for 5 hours. After evaporating most of the methanol, a sufficient amount of water was added to obtain an emulsion. A clear white precipitate appeared when quantitative sodium chloride was added, and the crude product was obtained by suction filtration.
  • Example 5 Except for using 4-aniline-6- (4, -sulfonylaminophenylamino) -1,3,5-triazine instead of aniline disubstituted tripolychlorazine, the procedure was carried out in Example 5 to obtain the title compound. The rate is 88%.
  • the title compound was obtained in the same manner as in Example 5 except that 4-aniline-6- (4'-methylaniline) -1,3,5-triazine was used instead of aniline disubstituted tripolychlorazine.
  • the yield was 64 °. /. .
  • the title compound was obtained in the same manner as in Example 5 except that 4-aniline-6- (3'-methoxyaniline) -1,3,5-triazine was used instead of aniline disubstituted tripolychlorazine.
  • the yield was 75. % '.
  • Biacore 3000 was used to study the interaction of piperazine triazines with cyclooxygenases (COX-1 and COX-2)
  • BIACORE3000 (BIACORE AB, Uppsala, Sweden) (Amersham), binding experiments of compounds with cyclooxygenase (COX-1 and COX-2) were performed at room temperature.
  • the chip and buffer solution are as follows: CM5 chip, EDC, NHS, ethanolamine, HBS-EP (purchased from BIACORE AB (Uppsala, Sweden)) 0
  • the test inflammatory agent was 0.2% Carrageenin.
  • Fifty healthy mice weighing 22 to 25 g were selected and randomly divided into groups: piperazine triazine compounds 50 mg / kg, intragastrically or intraperitoneally; indomethacin 10 mg / kg, intragastrically; negative control Groups were given the same volume of saline.
  • the right foot plantar of mice was injected subcutaneously with 20 ⁇ carrageenan.
  • the left and right feet were cut along the ankle joint and weighed.
  • the administration group, the control group, and the positive group were compared. Differences in the drug control group were calculated by statistical analysis to obtain the average, SD, p-value and percent inhibition.
  • Table 2 The experimental results are shown in Table 2.
  • the preparation method of the piperazinetriazine compound of the present invention has the advantages of mild reaction conditions, abundant raw materials and easy availability, simple operation and post-treatment, and the like.
  • the piperazine triamidine compounds of the present invention have strong anti-inflammatory activity in computer virtual screening and cyclooxygenase (COX-1 and COX-2) binding experiments and various experimental animal models, and can be used as anti-inflammatory drugs. They have a highly selective blocking effect on COX-2.
  • the compound of the present invention can inhibit the mouse carrageenan foot swelling model, and the intensity of the action increases with the administered dose.
  • Compound Ic was effective by intraperitoneal injection of 6.25 mg / kg, and effective by oral administration of 25 mg / kg.
  • the compounds of the present invention have very low toxicity.
  • the compound of the present invention can be used for preparing a medicament for treating an inflammatory disease.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Rheumatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pain & Pain Management (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur des composés de pipérazine triazine, et leurs sels pharmacocompatibles, de formule (I) dans laquelle: R1 est hydrogène, C1-C4alkyle, aryle, aryle substitué, aralkyle, C1-C4alkanoyle, aroyle ou C3-C7cycloalkyle; R2 et R3 sont respectivement, aryle substitué, aralkyle, C1-C4alkaryle ou C3-C7cycloalkyle; X est N; R7, O, S; R4 et R6 sont respectivement hydroxyle ou C1-C6alkyle; R5 est hydroxyle, C1-C6alkyle, -C(O)R8,-(CH2)mR8,-CH2CH=CHR8,-C(O)OR8,--C(O)OR8 ou S(O)2R8, m est 0,1,2 ou 3; R7 est hydrogène, hydroxyle ou C1-C6alkyle; R8 est hydrogène, hydroxyle, aryle, hétéroaryle, un radical hétérocyclique ou C2-C6alcényle. Lesdits composés de pipérazine triazine se sont avéré être des inhibiteurs de l'époxy synthase (COX-1 et COX-2), ayant un effet curatif fin et préventif sur les inflammations cliniques, lors de criblages virtuels informatisés, d'expériences combinées sur l'époxy synthase (COX-1 et COX-2), et d'essais pharmacologiques. L'invention porte également sur l'obtention desdits composés et sur des préparations pharmaceutiques les contenant.
PCT/CN2004/001368 2003-12-19 2004-11-29 Composes de piperazine triazine, leur obtention, et preparations pharmaceutiques les contenant WO2005058875A1 (fr)

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CNA2003101227211A CN1629157A (zh) 2003-12-19 2003-12-19 哌嗪三嗪类化合物、其制备方法及药物组合物
CN200310122721.1 2003-12-19

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Cited By (1)

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Publication number Priority date Publication date Assignee Title
WO2007095812A1 (fr) * 2006-02-27 2007-08-30 Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences Composés triazine [1,3,5] substitués, procédés de préparation et utilisations de ceux-ci

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Publication number Priority date Publication date Assignee Title
KR102310128B1 (ko) 2014-07-14 2021-10-06 주식회사 포스코 트리아진-피페라진 골격을 갖는 알파-헬릭스 유사체 및 이의 제조방법

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US4722806A (en) * 1982-02-19 1988-02-02 The B. F. Goodrich Company Alkylated polyalkylenepolyamines, substituted oxo-piperazinyl-triazines and UV light stabilized compositions
US4654384A (en) * 1983-01-14 1987-03-31 Ciba-Geigy Corporation Basic water-soluble bis-(β-azo-α-naphtholamino)-triazine compounds
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US5519121A (en) * 1994-03-03 1996-05-21 Bayer Aktiengesellschaft Triazinyl-amino bridge-containing disazo dyestuffs
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WO2003066099A1 (fr) * 2002-02-05 2003-08-14 Yamanouchi Pharmaceutical Co., Ltd. Derives de 2,4,6-triamino-1,3,5-triazine

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WO2007095812A1 (fr) * 2006-02-27 2007-08-30 Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences Composés triazine [1,3,5] substitués, procédés de préparation et utilisations de ceux-ci

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