WO2002072049A1 - Compositions medicamenteuses servant a stimuler la croissance capillaire - Google Patents

Compositions medicamenteuses servant a stimuler la croissance capillaire Download PDF

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Publication number
WO2002072049A1
WO2002072049A1 PCT/JP2002/001740 JP0201740W WO02072049A1 WO 2002072049 A1 WO2002072049 A1 WO 2002072049A1 JP 0201740 W JP0201740 W JP 0201740W WO 02072049 A1 WO02072049 A1 WO 02072049A1
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WO
WIPO (PCT)
Prior art keywords
lower alkyl
oxide
dihydro
pyridine
hair
Prior art date
Application number
PCT/JP2002/001740
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English (en)
Japanese (ja)
Inventor
Wataru Uchida
Katsumi Sudoh
Yuzo Matsumoto
Original Assignee
Yamanouchi Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yamanouchi Pharmaceutical Co., Ltd. filed Critical Yamanouchi Pharmaceutical Co., Ltd.
Priority to JP2002571008A priority Critical patent/JPWO2002072049A1/ja
Publication of WO2002072049A1 publication Critical patent/WO2002072049A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems

Definitions

  • the present invention relates to a pharmaceutical composition for hair growth comprising an aromatic ring fused oxazine derivative or a salt thereof as an active ingredient.
  • Alopecia can be broadly classified into mild alopecia caused by abnormalities in the hair growth cycle and rapid alopecia due to physical or mental stress.
  • human scalp hair has 3 to 7 years of anagen, 2 to 3 weeks of regression, and 4 to 6 months of telogen.Repeats three cycles: the ability to maintain hair, especially caused by abnormalities in this hair growth cycle
  • mature alopecia also known as male pattern baldness or androgenic alopecia
  • the growth period is shortened and the telogen is prolonged gradually, and the hair, which is the anagen, is relatively reduced.
  • the hair shaft elongates due to cell division in the growth phase of hair matrix cells separated from Pavila cells, and is maintained buried in the outer root sheath during the telogen phase, and no elongation is observed. Consequently, shortening anagen and prolonging the telogen shorten terminal hair length.
  • the size of the follicle fluctuates with the hair cycle, and the follicle enlargement is observed especially during the transition from telogen to anagen.
  • the size of the anagen hair follicle at this time is the thickness and height of the hair shaft that differentiates from the hair mother cell! Because of the correlation, the hair follicles at the bald area in age-related alopecia are not sufficiently enlarged compared to normal hair follicles, and the hair follicles (hair ). In other words, age-related alopecia can be said to be a miniature dwarf due to shortening of the anagen phase in the hair cycle and shrinking of the hair follicle, and thinning of the hair.
  • age-related alopecia is due to the effects of male hormones, its frequency increases with puberty, adolescence and aging. Symptoms are so-called “balding”, and most of them have bald areas localized to the frontal and parietal regions. The bald spots may occur alone or simultaneously. As mentioned above, the terminal hairs shrink and regrown as they regrow, resulting in the receding of the hairline on the frontal region and the bald area on the parietal region, which gradually expand and fuse. Eventually, all of the hair is removed except for the back and temporal regions. Age-related alopecia is predominantly male, but also affects women and children. In that case, the hair on the frontal region, temporal region or parietal region becomes thinner as in men. It is extremely rare to have complete hair loss like a man.
  • minoxidil which was initially developed as an oral antihypertensive drug, has attracted attention as a post-marketing side effect of minoxidil.
  • K-channel openers those known for their hair-growth effects include pinacidil, nicorandil, cromakalim, and diazoxide (all disclosed in Japanese Patent Application Publication No. 10-203935), 4- [[(Cyanoimino) [(1,2,2-trimethylpropyl) amino] methyl] amino] benzonitrile (see Japanese Patent Application No. 2001-515034), spirocyclic benzopyran The imidazolines (see JP-A-6-510060) are fisted.
  • the present inventors have conducted intensive studies on the hair-growth activity of a compound having a ⁇ channel opening action. As a result, an aromatic-ring-fused oxazine derivative or a salt thereof having a completely different structure from minoxidil, which is currently commercially available and widely used as a therapeutic agent for alopecia, In addition, it was confirmed that Minoxidil had a hair-growth effect equivalent to or better than Minoxidil, and the present invention was completed.
  • a pharmaceutical composition for hair growth comprising an aromatic condensed oxazine derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.
  • R 1 , R 2 and R 3 the same or different and a hydrogen atom or lower alkyl.
  • R 4 a hydrogen atom, lower alkyl or a group represented by the formula (II).
  • ⁇ hydrogen atom, lower alkyl, lower alkylene monoaryl, -CO-lower alkyl, carpamoyl which may be substituted by one or two lower alkyls, or two-port.
  • R 5 , R 6 , R 7 and R 8 the same or different and may be substituted with a hydrogen atom, halogen, lower alkyl optionally substituted with one or more halogen, -0-lower alkyl, cyano, nitro, one or two lower alkyl optionally substituted with Amino, -NHCO- lower ⁇ alkyl, -N (lower alkyl) CO- lower alkyl, -NHS0 2 - lower alkyl, -S0 2 - lower alkyl, or - S0 2 -Ariel. Or,
  • R 5 and R 8 a hydrogen atom.
  • R 6 and R 7 together with the adjacent two carbon atoms, at least two nitrogen source 5- or 6-membered heterocyclic ring which has a substituent and may further have an oxygen atom, a sulfur atom or a nitrogen atom.
  • R 5 , R 6 and R 8 identical or different, substituted by hydrogen atom, halogen, lower alkyl optionally substituted with halogen, -0-lower alkyl, cyano, nitro, one or two lower alkyls is optionally Amino, -NHCO- lower alkyl, -N (lower alkyl) CO- lower alkyl, -NHS0 2 - lower alkyl, -S0 2 - lower alkyl, or - S0 2 - Ariru.
  • R 7 absent or N-oxide together with X.
  • R 9 a group selected from the group consisting of a hydrogen atom and lower alkyl.
  • 1 to 4 groups may be present on the ring.
  • compositions for hair growth comprising the compound represented by the above general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient, preferably, 2- (3,4-dihydro-2,2-dimethyl -6-nitole -2H-1, 4-benzoxazine-4-ynole) pyridine 1-oxide (hereinafter referred to as “compound 1”), 2- (7,8-dihydro-6,6-dimethyl-6H) -[1,4] oxazino [2,3-/] [2,1,3] benzoxaziazol-8-yl) pyridine 1-oxide (hereinafter, referred to as “compound 2 J”) or 2- (6-cyano-3,4-dihydro-2,2-dimethyl-2H-1,4-benzoxazine-4-inole) pyridin 1-oxide (hereinafter, referred to as “compound 3”), or a pharmaceutical preparation thereof
  • the present invention relates to a compound represented by the above general formula (I), preferably compound 1, compound 2 or compound 3 for the production of a hair restorer and a hair restorer which is a therapeutic agent for Z or age-related alopecia. More preferably, it relates to the use of compound 3, or a pharmaceutically acceptable salt thereof.
  • the therapeutic efficacy of the compound represented by the above general formula (I), preferably compound 1, compound 2 or compound 3, more preferably compound 3, or a pharmaceutically acceptable salt thereof is provided.
  • a hair growth method comprising administering an amount to a patient, and a hair growth method which is a method for treating Z or age-related alopecia.
  • the present invention relates to a novel use of a benzoxazine derivative represented by the following general formula, which is disclosed in European Patent Applications EP432893 and EP500319.
  • K It is disclosed as a channel opener. Further, the detailed description of the invention in the publication describes that peripheral vasodilation based on K channel opening activity is useful for alopecia or dysplasia. However, there is no description that the compound is useful for those symptoms or has a hair-growth effect.
  • lower alkyl refers to C Les 6 alkyl; e.g. methylation, Echiru, propyl, isopropyl Honoré, butyl, tert- butyl, pentyl, neopentyl, hexyl and the like to, Preferably, it is methyl, ethyl, propyl, or isopropyl of C 1-3 alkyl.
  • “Lower alkylene” means C 1-6 alkylene, and specific examples include methylene, ethylene, propylene, dimethylmethylene, and 2,2-dimethylpropylene.
  • Aryl means a C 6-14 monocyclic to tricyclic aromatic ring which may have a substituent, and preferably phenyl, naphthyl and the like. Acceptable substituents include lower alkyl, -0-lower alkyl, rho, logen, nitro, cyano and the like.
  • Halogen includes, for example, fluorine, chlorine, bromine and iodine atoms. Accordingly, “lower alkyl optionally substituted with halogen” means the above “lower alkyl” which may be substituted or unsubstituted with the above “halogen”. Specific examples thereof include, in addition to the above “lower alkyl”, fluoromethyl, trifluoromethyl, trifluoroethyl, pentafluoroethyl, trichloromethyl and the like.
  • the term “5- or 6-membered heterocyclic ring having at least two nitrogen atoms and optionally having an oxygen atom, a sulfur atom, or a nitrogen atom” is specifically, for example, oxaziazole or thiadiazole , Triazole, pyrazine, oxaziazine and the like.
  • the compound of the present invention represented by the general formula (I) may contain an asymmetric carbon atom depending on the type of the substituent, and an optical isomer based on this may exist.
  • the present invention includes all mixtures and isolated forms of these optical isomers.
  • the compound of the present invention may form an acid addition salt.
  • the salt is included in the present invention.
  • inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, etc., formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, conodic acid, Acid addition salts with organic acids such as fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, P-toluenesulfonic acid, aspartic acid or glutamic acid, and the like.
  • the present invention includes various hydrates, solvates, and substances having crystalline polymorphs of the compound of the present invention and pharmaceutically acceptable salts thereof.
  • the compounds of the present invention include all compounds that are metabolized in vivo and converted into the compound having the general formula (I) or a salt thereof, so-called prodrugs.
  • Examples of the group that forms the prodrug of the present invention include those described in Prog. Med. 5: 2157-2161 (1985), and “Developing Pharmaceuticals”, 1990, Hirokawa Shoten, Vol. 7, Molecular Design 163-198. And the groups described in the above.
  • the compounds of the present invention represented by the general formula (I) particularly preferred are the 2- (3,4-dihydro- compounds described in JP-A-4-178375 and JP-A-5-70464.
  • the compound of the present invention represented by the general formula (I) can be easily obtained by the production method described in the above-mentioned JP-A-4-178375 or JP-A-5-70464, or according to it.
  • one or more active substances of the compound of the present invention represented by the general formula (I) are contained in an amount of 0.001 to 99.999% by weight based on the total amount of the hair restorer. It is more preferably 0.001 to 10% by weight, particularly preferably 0.003 to 3% by weight.
  • the drug of the present invention is generally used by using at least one compound of the present invention represented by the general formula (I) and a simple substance, excipient, and other additives usually used for formulation. Can be prepared by the following method.
  • Administration is oral, such as tablets, pills, capsules, granules, powders, and liquids; injections, such as intravenous and intramuscular injections; or parenteral, such as suppositories, nasally, transmucosally, and transdermally. May be used.
  • the one or more active substances comprise one or more inert diluents such as lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone. Mixed with magnesium metasilicate aluminate and the like.
  • the composition may contain additives other than an inert diluent, for example, a lubricant such as magnesium stearate, a disintegrant such as calcium cellulose dalycholate, a stabilizer such as ratatose, glutamic acid or It may contain an auxiliary agent for melting angle such as aspartic acid.
  • a lubricant such as magnesium stearate
  • a disintegrant such as calcium cellulose dalycholate
  • a stabilizer such as ratatose
  • glutamic acid glutamic acid
  • It may contain an auxiliary agent for melting angle such as aspartic acid.
  • tablets or pills may be coated with sugar coating such as sucrose, gelatin, hydroxypropylsenorellose, hydroxypropynolemethinole cellulose phthalate or the like, or with a gastric or enteric film.
  • Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs and the like, and commonly used inert diluents, such as purified water , Containing ethanol.
  • the composition may contain, in addition to the inert diluent, adjuvants such as wetting agents and suspending agents, sweetening agents, flavoring agents, fragrances, and preservatives.
  • Injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions.
  • Aqueous solutions and suspensions include, for example, distilled water for injection and physiological saline.
  • Non-aqueous solutions and suspensions include, for example, propylene glycol, polyethylene glycol and olive oil, vegetable oils, alcohols such as ethanol, polysorbate 80 and the like.
  • Such compositions may also contain adjuvants such as preserving, wetting, emulsifying, and dispersing agents, for example, stabilizing agents such as lactose, solubilizing agents such as glutamic acid-aspartic acid, and the like. .
  • this Are sterilized by, for example, filtration through a pateria retaining filter, blending of a bactericide or irradiation. These can also be used by preparing a sterile solid composition and dissolving it in sterile water or a sterile injection solvent before use.
  • Transdermal preparations for parenteral administration include ointments, lotions, cataplasms, gels, creams, solutions, sprays, baths, patches and the like.
  • one or more active ingredients may contain one or more inert additives, for example, hydrocarbons such as petrolatum, squalane, liquid paraffin, higher alcohols such as stearyl alcohol, cetanol, and the like.
  • Lower alkyl esters of higher fatty acids such as isopropyl myristate and isopropyl palmitate; animal fats and oils such as lanolin; polyhydric alcohols such as glycerin and propylene glycol; polyethylene glycols such as McGolle 400 and McGoal 4000 Glycerin fatty acid esters such as glyceryl monostearate, sodium lauryl sulfate, polyethylene glycol monostearate, surfactants such as polyxethylene alkyl ether phosphoric acid, sorbitan sesquiate, etc., lactic acid, sodium taenoate, Sodium carbonate Beam, various salts such as anhydrous sulfuric Natoriumu, ethanol, ⁇ , resin, water and optionally by Paraokishi benzoate, para Okishi acid Echiru, Paraokishi propyl benzoate, is mixed with a preservative such as Paraokishi butyl benzoate.
  • a transdermal agent can be prepared by mixing 30.3 g of the compound, 30 mL of ethanol, and 50 mL of propylene glycol, and adding distilled water to a total volume of 100 mL.
  • the pharmaceutical composition for hair restoration according to the present invention may be a lotion, an emulsion, a cream, an ointment, a pack or the like, or a hair coating, a hair lotion, a hair term, a hair conditioner, a shampoo, It can be in the form of a hair restorer such as rinse, hair elixir, hair mist, and foam.
  • a hair restorer such as rinse, hair elixir, hair mist, and foam.
  • Excipients, pigments, female hormonal agents, antiandrogenic agents, and the like can be appropriately compounded within a range that does not impair the purpose of the present invention.
  • the daily dose is about 0.0001 to 50 mg / kg of active ingredient per body weight, preferably about 0.001 to 10 mg / kg, more preferably 0.01 to 1 mg / kg. It is administered once or in 2 to 4 divided doses. When administered intravenously, the daily dosage should be about 0.0001 to 1 mg / kg, preferably about 0.0001 to 0.1 mg / kg, of the active ingredient per body weight. Administration. In the case of transdermal administration, the daily dosage is about 0.01 to 200 mg, preferably about 0.01 to 100 mg, and more preferably about 0.01 to 10 mg of the active ingredient per person. It is administered once or more than once a day. The dose is appropriately determined depending on the individual case in consideration of symptoms, age, sex, and the like. Industrial applicability
  • the pharmaceutical composition for hair growth excellent or the pharmaceutical composition for the treatment of adolescent alopecia can be provided.
  • Table 1 shows the structures of Compound 1, Compound 2 and Compound 3 used in the following test examples. (table 1 )
  • Test Example 1 Test of hair growth effect of compound 1, compound 2 and minoxidil in mice Animals used: C3H / HeNCrj male mice (7 weeks old), 10 cases per group.
  • a shaved surface of about 2 cm ⁇ 2 cm was formed on the back of the mouse using an electric clipper and an electric shaver, and 0.1 mL of the test substance solution was applied once a day for 7 days.
  • Test Example 2 Test of hair growth effect of compound 3 and minoxidil in mice Animals used: C3H / HeNCrj male mice (5 weeks old), 10 cases per group.
  • the back of the mouse is about 2cmX using an electric palycan and an electric sealer.
  • a 2 cm shaved surface was prepared, and 0.1 mL of the test substance solution was applied once a day for 28 days.
  • the solution used was a 70% aqueous ethanol solution.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
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  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des compositions médicamenteuses servant à stimuler la croissance capillaire et contenant en tant que substance active des dérivés d'oxazine aromatique à cycles accolés ou des sels pharmaceutiquement acceptables correspondants.
PCT/JP2002/001740 2001-02-27 2002-02-26 Compositions medicamenteuses servant a stimuler la croissance capillaire WO2002072049A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2002571008A JPWO2002072049A1 (ja) 2001-02-27 2002-02-26 育毛用医薬組成物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2001-51593 2001-02-27
JP2001051593 2001-02-27

Publications (1)

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WO2002072049A1 true WO2002072049A1 (fr) 2002-09-19

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PCT/JP2002/001740 WO2002072049A1 (fr) 2001-02-27 2002-02-26 Compositions medicamenteuses servant a stimuler la croissance capillaire

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7378415B2 (en) 2004-09-30 2008-05-27 Roche Palo Alto Llc Benzoxazine and quinoxaline derivatives and uses thereof
CN102977117A (zh) * 2012-11-26 2013-03-20 盛世泰科生物医药技术(苏州)有限公司 一种6-溴-2,2-二甲基-2h-吡啶并[3,2-b][1,4]恶嗪-3(4h)-酮的合成方法
US9539260B2 (en) 2011-12-22 2017-01-10 Novartis Ag Dihydro-benzo-oxazine and dihydro-pyrido-oxazine derivatives

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0432893A2 (fr) * 1989-11-08 1991-06-19 Yamanouchi Pharmaceutical Co. Ltd. Dérivés de benzoxazine, leur préparation et compositions pharmaceutiques les contenant
US5278158A (en) * 1991-02-18 1994-01-11 Yamanouchi Pharmaceutical Co., Ltd. Oxazinobenzazole compounds

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0432893A2 (fr) * 1989-11-08 1991-06-19 Yamanouchi Pharmaceutical Co. Ltd. Dérivés de benzoxazine, leur préparation et compositions pharmaceutiques les contenant
US5278158A (en) * 1991-02-18 1994-01-11 Yamanouchi Pharmaceutical Co., Ltd. Oxazinobenzazole compounds

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7378415B2 (en) 2004-09-30 2008-05-27 Roche Palo Alto Llc Benzoxazine and quinoxaline derivatives and uses thereof
US9539260B2 (en) 2011-12-22 2017-01-10 Novartis Ag Dihydro-benzo-oxazine and dihydro-pyrido-oxazine derivatives
US9763952B2 (en) 2011-12-22 2017-09-19 Novartis Ag Dihydro-benzo-oxazine and dihydro-pyrido-oxazine derivatives
CN102977117A (zh) * 2012-11-26 2013-03-20 盛世泰科生物医药技术(苏州)有限公司 一种6-溴-2,2-二甲基-2h-吡啶并[3,2-b][1,4]恶嗪-3(4h)-酮的合成方法

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