WO1989005803A1 - Derives de 3,4-dihydro-2h-1,3-benzoxazine et leur utilisation en medecine - Google Patents

Derives de 3,4-dihydro-2h-1,3-benzoxazine et leur utilisation en medecine Download PDF

Info

Publication number
WO1989005803A1
WO1989005803A1 PCT/JP1988/001306 JP8801306W WO8905803A1 WO 1989005803 A1 WO1989005803 A1 WO 1989005803A1 JP 8801306 W JP8801306 W JP 8801306W WO 8905803 A1 WO8905803 A1 WO 8905803A1
Authority
WO
WIPO (PCT)
Prior art keywords
dihydro
group
benzoxazine
compound
derivative
Prior art date
Application number
PCT/JP1988/001306
Other languages
English (en)
Japanese (ja)
Inventor
Soichi Sakane
Katsushi Eziri
Manzo Shiono
Yoshiji Fujita
Johji Yamahara
Original Assignee
Kuraray 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 Kuraray Co., Ltd. filed Critical Kuraray Co., Ltd.
Publication of WO1989005803A1 publication Critical patent/WO1989005803A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
    • C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
    • C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D265/16—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with only hydrogen or carbon atoms directly attached in positions 2 and 4

Definitions

  • the present invention relates to a novel compound having a 3,4-dihydro-2 -1,3,3-benzoxazine skeleton and a pharmaceutical use thereof.
  • the above-mentioned anti-peptic ulcer agent is a so-called aggressive anti-ulcer agent that attenuates the aggressive factor.] 5)
  • This type of anti-ulcer agent often has side effects, 0 the other hand has the disadvantage that you have with the easy to relapse and Ru quit, Oh also this has little it takes drawbacks defense type antiulcer agent to enhance the defense factor] ?, it was excellent for this type of anti At present, the development of ulcers is desired.
  • non-steady-state analgesic drugs have problems such as gastrointestinal tract side effects in anti-inflammatory drugs, and in the field of analgesic anti-inflammatory drugs, develop highly active drugs with few side effects.
  • tissue damage due to excessive production of reactive oxygen has been deeply involved in autoimmune diseases, inflammation, circulatory diseases and especially ischemic diseases. It has been clarified that the development of a drug effective against tissue damage due to active oxygen is also desired.
  • the purpose of the present invention is to provide an excellent anti-ulcer effect and an effect of improving dysuria.
  • Another object of the present invention is to provide a pharmaceutical use of the novel compound> that is, to provide a pharmaceutical composition containing the compound as an active ingredient.
  • R 1 is A Le key group, Table Wa heterocyclic group but it may also have to have a Rua rie group or substituent having a substituent group having a substituent, R 2, R 3 and R 4 each represent a hydrogen atom or a methyl group) 3,4-dihydro-2H-1,3-benzoxazine derivative or a pharmacologically acceptable salt thereof [hereinafter referred to as 3, 4 4-dihydro-2H-1,3-benzoxazine derivative (I)], and 2 a therapeutically effective amount of 3,4-dihydro-2H-1,3. -Achieved by providing a pharmaceutical composition comprising at least one benzoxazine derivative (I) and a pharmaceutically acceptable excipient o
  • R 1 represents an alkyl group having a substituent, an aryl group having a substituent, and a heterocyclic group optionally having a substituent.
  • R 1 an alkyl group having a substituent represented by R 1 will be described.
  • An alkyl group is, for example, methyl, ethynole-butane pinole, isopropynole, butynole, or isobutene.
  • the alkoxy group is, for example, methoxy, ethoxy, propoxy, isobroxoxy, butoxy, t-butoxy, silicone, etc. Mouth pentrox, etc.] 9, and the territory of the roxoxy group is! J ebenoki, p-chlorophenoxy, p-methoxy. Represented by Fenokishi.
  • Substituted amino groups include, for example, methylamino, dimethylamino, methylamino, (1—phenylenepiperidine-14-amino) amino. N, N — methylone N — N-methyl, N-C3, 4 — Dimethyl N-methyl)-Representative of N-methyl-mino, etc.
  • aryl groups include phenyl and naphthyl, and the substituents of these aryl groups include fluorine and Halogen atoms such as chlorine and bromine; lower metals such as methoxy, ethoxy, propoxy, impoxy> butoxy, t-butoxy, etc.
  • Heterocyclic groups include pyrrolidine, pyrazolyl, imidazolinole, imitazolinole, benzimitazole, oxazolinole, and bezine. ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ ,
  • the substituents possessed by these heterocyclic groups include benzyl, 0-cyclobenzene, p-cyclobenzene, p-methoxybenzene, 2 , 3, 4 1 Tri-methyl benzoin p-methyl benzene Ginore, Benzhydrinore, — f pyrinole) Veginore, 1 (p — Cloth mouth Feninole) Veginole, bis (p Zeninole) methinole, p — nitrobenzene ginole,-dimethyleneamine benzone ole, p-sine benzene enole, phenethyl, P-methodine Sifethylene 3 ⁇ 4 an arylalkyl group which may have any substituents; alkenyl phenols such as cinnamyl, 0-chloro Mouth fever, p — Chloro feninole, 0-Methoxy fever, p-Metfoxy, 2, 3,
  • Alkoxy bases include methoxy carbonyl, ethoxy carbonyl, brokoxy, etc. ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ 0 ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ 0 ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ 0 0 ⁇ ⁇ ⁇ ⁇ ⁇ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
  • An aryl group is represented by, for example, phenyl, naphthyl, etc., and these aryl groups are
  • the substituent may be a methoxy group; a carboxylic group; a methoxy group; a ethoxy group; an ethoxy group;
  • Nore Isopro Pokishika Nore Boninore, Butokishikaru Bonnore, t-butokishikarbonil, etc.
  • R 1 represents the piperazinyl Li isoxazolidinyl, Pi Li di Le> pyrimidone isoxazolidinyl, typified in etc.
  • piperazinyl La Gini Le examples include lower alkyl, methyltin, propyl, isopropynole, butynole, imbutinole, t-butynole and the like.
  • R 6 represents a hydrogen atom or a lower alkyl group
  • R 7 represents a substituted or unsubstituted lower alkyl group or a substituted or unsubstituted heteroalkyl group.
  • X 2 represents an alkylene chain which may have a side chain, and ⁇ , ⁇ , and ⁇ 4 are as defined above!
  • R 8 represents an aryl group which may have a substituent or a heterocyclic group which may have a substituent, and X 3 may have a side chain. Represents an alkylene chain, and R 2 and R 4 are as defined above.
  • R 9 represents a hydroxyl group, an alkoxy group or an amino group
  • X 4 represents an alkylene chain which may have a side chain.
  • R 2 and R 4 are as defined above.
  • X 5 represents an alkylene chain which may have a side chain.
  • R 11 is a heterocyclic group which may optionally have a ⁇ rie group or substituent having a substituent and Table Wa,, 11 3 and 1 4 are passing above)
  • R 12 represents an alkyl group which may have a substituent, and R 2 > R 3 , R 4 and X 3 are as defined above
  • 4-Dihydro 2H-1,3-benzoxazine derivatives and pharmacologically acceptable salts thereof have anti-ischemic effects, ameliorating effects on abnormal urination such as pollakiuria, It has pharmacological effects such as calcium antagonism and anticholinergic effects]
  • 3,4-dihydro 2H-1 represented by the general formulas ( ⁇ ) to Sir 3,4-Dihydroxy-2H-1'3_benzoxazine derivatives, including 3,3-benzoxazine derivatives and their pharmacologically acceptable salts
  • Class (I) has high antiperoxidation activity o
  • the pharmacologically acceptable salts of the 3,4-dihydro-2 2-1,3-benzoxazine derivative represented by the general formula (I) are hydrochloric acid, Salts of mineral acids such as sulfuric acid; methansulfonate, ⁇ -transencenolephonic acid Salts of organic sulfonates such as acetic acid, propionic acid, and oxalate Acid, konno, citric acid, maleic acid, fumanoleic acid, tartar Salts of organic carboxylic acids such as acid, linoleic acid, and citric acid; salts of alkali metals such as sodium and potassium; calcium and magnesium Nesium 3 ⁇ 4 which may include salts of earth metals, salts of aluminum, salts of zinc, etc.
  • the 3,4-dihydro-2H-1,3-benzoxazine derivative represented by the general formula (I) can be produced, for example, by the following method9.
  • the pharmacologically acceptable salt of the 3,4-dihydro-2H-1,3-benzoxazine derivative represented by the general formula (I) can be obtained by the usual salt formation reaction. easily prepared from the 3,4-dihydro-2H-1,3-benzoxazine derivative represented by the general formula (I) and a desired acid or base o
  • the 3,4-dihydro-2H-1,3-benzo-aged xazine derivative (I) used is a compound having the above-mentioned scent.
  • the dose of the test compound and the ulcer coefficient in the rats to which the test compound was administered were compared with the ulcer index in the rats without injection.
  • a ddY male mouse (body weight: about 18 ?, group 8 ⁇ : L0 animals) was orally injected with a liquid in which the test compound was suspended in powder of Arabic rubber.
  • a 29 & brilliant blue solution (0.1 ⁇ 10 mouse body weight) was infused through the tail vein, and 60 minutes later, a 1-acetic acid aqueous solution (0. l ⁇ Zl09 mouse weight) was administered intraperitoneally o 5 minutes after the administration jl 5 minutes mouse The stretcin was observed and the analgesic effect was determined.
  • Table 4 and Table 5 show the dose of the test compound: the amount and the inhibition rate of Writiiing and Permeability in the administered mouse.
  • Ethanol linoleate-Tocopherol or the compounds (1) to (96) of the present invention are each added to the linoleic acid ester at a rate of 0.0 20 Addition and mixing to prepare a sample solution 0 20 m of these samples were taken under A0M conditions (97.8 ° C, aeration 2.33 ⁇ sec) and measured the time to reach a POV (peroxide value) of 100 meq / k ? o As a result, the POV of k "-tocopherol was 1.75 hours, Compound (3) was 2.8 hours o Similarly, compounds (1), (2) and (4)-(96) were all higher antioxidant properties than "-tocopherol" 0
  • test compound A predetermined amount of the test compound was suspended and administered orally to a ddY male mouse (body weight: 18; 8 to 10 animals per group) by suspending the compound in the end of a rabbi rubber. One hour later, 3.1 mg / mg of cyanobacterium was administered intravenously. After completion of administration of xianhicalum 180 Mice that did not stop breathing after more than a second were counted as survivors and the survival rate was determined. O The results are shown in Table 6.
  • a nutrient solution (Naa: 120.4 mM, K: .8 mM, aerated with 95% 02-5 ⁇ C02 mixed gas) was incubated at 37 ° C, and the mormot bladder section was kept at 37 ° C.
  • the 3,4-dihydro-2H-1,3-benzozoazine derivative (I) of the present invention has a remarkable anti-peptic ulcer effect, analgesic anti-inflammatory effect and anti-inflammatory effect.
  • the 3.4-dihydro-2H-1,3-benzoxazine derivative (I) of the present invention can be used for peptic ulcer disease, anti-inflammatory disease and the like. O It is useful as a therapeutic agent for various diseases such as cerebrovascular disorder, ischemic heart disease, and urinary abnormalities o
  • the dose of the 3,4-dihydro-2H-1,3-benzoxazine derivative (I) depends on the disease, the severity of the patient, the drug tolerance, etc.] 9 Varies, usually between 5 and 2000, preferably between 50 and 600 per adult per day, preferably in single or divided doses o
  • the mode of administration can be in any form suitable for administration.
  • compositions containing at least one o3,4-dihydroxy-2H-1.3-benzodiazine derivative U) may be any desired pharmaceutical carrier, Excipients-prepared by conventional means using any pharmaceutically acceptable excipients, etc.o
  • the formulation is digested Desirably, it is provided in a form suitable for absorption from tubes.
  • Oral tablets and capsules are in unit dosage form, and may contain binders such as syrup, labiramu, gelatin, solvit, tragacan.
  • Excipients polyvinyl pyrrolidone, etc .
  • excipients such as lactose, corn starch, calcium phosphate, sorbit, glycin, etc.
  • Lubricants such as magnesium stearate, talc, polyethylene glycol, silica, etc.
  • a disintegrant such as potato starch; or an acceptable wetting agent, such as sodium raurylsulfate, which may contain any conventional excipients. Coating may be performed in a manner well known in the industry.
  • Oral liquid preparations can be aqueous or oily suspensions, solutions, syrups, elixirs, etc., or with water or other suitable vehicles before use.
  • j for example, Soviet Le bit shea Lock up, main Ji Le Cellulose, gnorecose / sugar syrup, gelatin, hydroxethylenol cellulose, canolepo, cinnamate porcelain Emulsifiers, for example, lentin, monofluorinated sorbitan, arabia, etc.
  • Non-aqueous vehicles such as oil, fractionated coconut oil,?
  • Preservatives such as methyl-P-hydroxybenzoate, P-Hydrogen, Fluoro-Like, Ricoh Reno, Echinore, etc .; Preservatives Contains hydroxypropyl benzoate and sorbin 0
  • a 3,4-dihydro-2H-1,3-benzoxazine derivative (I) may be added to a physiological saline solution and a bud for injection.
  • Sugar solution ⁇ Soluble in any solvent
  • compositions generally contain 3,4-dihydro-2H-1,3-benzoxazine derivatives (I) in an amount of about 0.01, depending on the form and the like.
  • O can contain up to 50% by weight, preferably about 0.1-20% by weight o
  • Example 1 Trimethylinohydroquinone 6.08 f (40 mmo ⁇ .), Monoethanol Noreamine 2.56 (42 mmo ⁇ ), Parahonore Aldehi Do
  • Example 2 9 In Example 1, the monoethanolamine was replaced with 42 mmoz, and instead of J ?, benzylamine, 3—aminomine resin, and 4-amino Methyl pyridin, 3 — morpholinopropylamine, 21- (11-imidazolyl) ethylamine, 2-(3,4-dimethine) (Kisifenil) Ethylamine, 41-Amino Anbi, Ethyl perfume or 3-Aminopyridine were used except for 42 rao £.
  • X represents a methylene group or a group represented by the formula: CHsSSCH 2-
  • a suspension consisting of 2.52 (84 mmo) of sodium aldehyde, 3.53 of sodium bicarbonate and 50 of ethanol was heated to reflux for 8 hours.
  • Methylene chloride was added to the obtained reaction solution, which was washed with water and dried over anhydrous magnesium sulfate.
  • the obtained solution was concentrated under reduced pressure, and ethyl ether was added, and the formed crystals were separated by filtration.
  • the crystals are washed with a mixture of ethyl ether, hexane and hexane, dried under reduced pressure, and have the following physical property values of 3,4-dihydro-3--3-ethoxy.
  • Trimethylinohydroquinone 6.08 (40 nimo), r-amino dairy 4.3 3 (42 nimo ⁇ ), paraformaldehyde 2.52 ⁇ C 84 mmo ⁇ ), 3.53 ⁇ (42 mmo.)
  • Baking soda and 50 ⁇ ethanol 50 ⁇ were heated under reflux for 8 hours.
  • 1N Hydrochloric acid (42 ⁇ ) was added to the obtained reaction solution, and the formed precipitate was separated by filtration and washed sequentially with water, ethanol and ethyl ether.
  • Example 1 5 ⁇ 4 2
  • N ⁇ —dimethyl thiocyanamine 42 (instead of 2 mmo-d) ?? 2-[N-(3, 1-methylamine)-methylamine] etheramine, 3-[ ⁇ -1, (3, 4-dimension) (Kifen) 1>J> 1) Mouth pinoleamine, 1- (2-aminoethyl) 1-41 Bencinolehyperazine, 1— (2-aminoethyl) 1-4- (11-1 Phenazine, 1- (3-aminophenol), 11- (2-aminoethyl), 41-benzhydrinole-hyperazine, 1- (3-amino 4-Benzhydryl perazine, 1-1 (2-Aminoethyl)-4-1 (2,
  • Mouth Pinore et al 1 1 (2-Amino ethyl) 1 4 1 [bis [4-Fonore orofeninoren] Mechinore] Pigin, 1-1 (3-a) Mino bropinole)-1 [Vis (4-phenolic mouth fu-nore) methinole] piperazine or 1-1 (2-aminoethyl) 1-4-1 (4- The reaction, separation and purification were carried out in the same manner as in Example 10 except that 42 mmo of pyridine was used.
  • Example 10 In place of N, N-dimethylethylamine 42 mmo ⁇ in Example 10) 41-to-one-closed benzinoleamine, 2,4—di Gross vents, Min 4, Gen 4, Gen 4, Gen 4, Gen 4, Gen 4, Gen 4, Gen 4 , 31 phenoxy benzene amide, 4 trifluoro benzene benzene amide, 4 — nitro benzene amide, 4 1-Dimethylamine, 4-Dimethylaminopopendinolemin, 4-Diaminobenzylamine, 4-Diaminomethylbenzoic acid, 4-Ami Nomethylyl harm, harm, butyl perfume, furfuramine, tenylamine, 2— (imidazoline 1-yl) ethylamine, 2—bi b Li di Bruno Echinore A Mi emissions, 2 -.
  • a novel 3,4-dihydroxyl-2H-1,3-benzoxazine derivative [1] useful as a medicament.
  • 3,4-Hydrogen 2H—1,3—Benzoxazine derivatives [1] are clearly evident from the results of the aforementioned pharmacological tests. Has excellent anti-peptic ulcer action, analgesic / anti-inflammatory action, anti-peroxidation action, anti-ischemic action, anti-frequent urinary action, calcium antagonism action, and anti- or anti-cholinergic action. , And high safety.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

Dérivés de 3,4-dihydro-2H-1,3-benzoxazine représenté par la formule générale (I), dans laquelle R1 représente un groupe alkyle substitué, un groupe aryle substitué ou un groupe hétérocyclique éventuellement substitué, et R2, R3 et R4 représentent chacun un atome d'hydrogène ou un groupe méthyle. Ces dérivés, ainsi que leurs sels acceptables en pharmacologie, permettent de soigner l'ulcère peptique ou de traiter le dysurie.
PCT/JP1988/001306 1987-12-24 1988-12-23 Derives de 3,4-dihydro-2h-1,3-benzoxazine et leur utilisation en medecine WO1989005803A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP32873187 1987-12-24
JP62/328731 1987-12-24

Publications (1)

Publication Number Publication Date
WO1989005803A1 true WO1989005803A1 (fr) 1989-06-29

Family

ID=18213545

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1988/001306 WO1989005803A1 (fr) 1987-12-24 1988-12-23 Derives de 3,4-dihydro-2h-1,3-benzoxazine et leur utilisation en medecine

Country Status (1)

Country Link
WO (1) WO1989005803A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5424321A (en) * 1993-12-08 1995-06-13 Alcon Laboratories, Inc. Compounds having both potent calcium antagonist and antioxidant activity and use thereof as cytoprotective agents
WO1996026924A1 (fr) * 1995-02-28 1996-09-06 Suntory Limited Derives d'arylpiperidine et d'arylpiperazine et medicaments contenant lesdits derives
US5646149A (en) * 1993-12-08 1997-07-08 Alcon Laboratories, Inc. Compounds having both potent calcium antagonist and antioxidant activity and use thereof as cytoprotective agents
US5691360A (en) * 1993-12-08 1997-11-25 Alcon Laboratories, Inc. Compounds having both potent calcium antagonist and antioxidant activity and use thereof as cytoprotective agents
US6482946B1 (en) 1999-11-05 2002-11-19 Dow Global Technologies Inc. High char yield benzoxazine compositions
WO2007012580A1 (fr) * 2005-07-26 2007-02-01 Basf Aktiengesellschaft Utilisation de tetrahydrobenzoxazines comme agents stabilisants
WO2007078335A3 (fr) * 2005-12-21 2007-11-29 Decode Genetics Inc Inhibiteurs de biaryl-azote-heterocycle de lta4h pour traiter l'inflammation
US9178237B2 (en) 2010-12-14 2015-11-03 Samsung Electronics Co., Ltd. Conductive composition and method of preparation, polymer thereof, and electrode, electrolyte membrane and fuel cell including the composition or polymer
WO2021115380A1 (fr) * 2019-12-10 2021-06-17 上海挚盟医药科技有限公司 Composé à effet neuroprotecteur, son procédé de préparation et son utilisation
CN115335366A (zh) * 2020-03-12 2022-11-11 卢森堡科学技术研究院 苯并噁嗪衍生物的类玻璃高分子
WO2023038044A1 (fr) * 2021-09-08 2023-03-16 株式会社カネカ Composition de benzoxazine et son utilisation

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3462266A (en) * 1967-09-05 1969-08-19 Eastman Kodak Co Photographic color diffusion transfer processes and elements
JPS6340153A (ja) * 1986-08-06 1988-02-20 Konica Corp 色素画像の堅牢性が改良されたハロゲン化銀写真感光材料

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3462266A (en) * 1967-09-05 1969-08-19 Eastman Kodak Co Photographic color diffusion transfer processes and elements
JPS6340153A (ja) * 1986-08-06 1988-02-20 Konica Corp 色素画像の堅牢性が改良されたハロゲン化銀写真感光材料

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Vol. 107, No. 7, 17 Aug. 1987 (17.08.87), (Columbus, Ohio, U.S.A.), AUGUSTO RIVERA et al., "Synthesis of benzoxazines. Part I", see Abstract No. 58947h, REV. COLUMB. QUIM., 1 3(2), 14-20 (1984). *
CHEMICAL ABSTRACTS, Vol. 58, (1963), (Columbus, Ohio, U.S.A.), W.J. BURKE et al., "Mono-1,3-benzoxazines from hydroquinone", see Abstract No. 11351a, J. ORG. CHEM., 28, 1098-1100 (1963). *
CHEMICAL ABSTRACTS, Vol. 60, (1964), (Columbus, Ohio, U.S.A.), CARL WEATHERBEE et al., "Alkylaminomethylhydroquinones and related compounds", see Abstract No. 439h, Trans. Illinois State Acad. Sci., 56(1), 12-18 (1963). *

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5424321A (en) * 1993-12-08 1995-06-13 Alcon Laboratories, Inc. Compounds having both potent calcium antagonist and antioxidant activity and use thereof as cytoprotective agents
US5646149A (en) * 1993-12-08 1997-07-08 Alcon Laboratories, Inc. Compounds having both potent calcium antagonist and antioxidant activity and use thereof as cytoprotective agents
US5691360A (en) * 1993-12-08 1997-11-25 Alcon Laboratories, Inc. Compounds having both potent calcium antagonist and antioxidant activity and use thereof as cytoprotective agents
WO1996026924A1 (fr) * 1995-02-28 1996-09-06 Suntory Limited Derives d'arylpiperidine et d'arylpiperazine et medicaments contenant lesdits derives
EP0757986A1 (fr) * 1995-02-28 1997-02-12 Suntory Limited Derives d'arylpiperidine et d'arylpiperazine et medicaments contenant lesdits derives
EP0757986A4 (fr) * 1995-02-28 1997-04-16 Suntory Ltd Derives d'arylpiperidine et d'arylpiperazine et medicaments contenant lesdits derives
US5723475A (en) * 1995-02-28 1998-03-03 Suntory Limited Arylpiperidine and arylpiperazine derivatives and medicament containing the same
US6482946B1 (en) 1999-11-05 2002-11-19 Dow Global Technologies Inc. High char yield benzoxazine compositions
US9840608B2 (en) 2005-07-26 2017-12-12 Basf Se Use of tetrahydrobenzoxazines as stabilisers
WO2007012580A1 (fr) * 2005-07-26 2007-02-01 Basf Aktiengesellschaft Utilisation de tetrahydrobenzoxazines comme agents stabilisants
US10294350B2 (en) 2005-07-26 2019-05-21 Basf Se Use of tetrahydrobenzoxazines as stabilisers
AU2006274052B2 (en) * 2005-07-26 2011-05-12 Basf Se Use of tetrahydrobenzoxazines as stabilisers
US9062267B2 (en) 2005-07-26 2015-06-23 Basf Se Use of tetrahydrobenzoxazines as stabilisers
US9951204B2 (en) 2005-07-26 2018-04-24 Basf Se Use of tetrahydrobenzoxazines as stabilizers
US9217115B2 (en) 2005-07-26 2015-12-22 Basf Se Use of tetrahydroberizoxazines as stabilisers
WO2007078335A3 (fr) * 2005-12-21 2007-11-29 Decode Genetics Inc Inhibiteurs de biaryl-azote-heterocycle de lta4h pour traiter l'inflammation
US7750012B2 (en) 2005-12-21 2010-07-06 Decode Genetics Ehf Biaryl nitrogen-heterocycle inhibitors of LTA4H for treating inflammation
US9178237B2 (en) 2010-12-14 2015-11-03 Samsung Electronics Co., Ltd. Conductive composition and method of preparation, polymer thereof, and electrode, electrolyte membrane and fuel cell including the composition or polymer
WO2021115380A1 (fr) * 2019-12-10 2021-06-17 上海挚盟医药科技有限公司 Composé à effet neuroprotecteur, son procédé de préparation et son utilisation
JP2023505554A (ja) * 2019-12-10 2023-02-09 シャンハイ ジムン バイオファーマ，インコーポレーテッド 神経保護効果を有する化合物およびその調製方法と用途
CN115335366A (zh) * 2020-03-12 2022-11-11 卢森堡科学技术研究院 苯并噁嗪衍生物的类玻璃高分子
WO2023038044A1 (fr) * 2021-09-08 2023-03-16 株式会社カネカ Composition de benzoxazine et son utilisation

Similar Documents

Publication Publication Date Title
CN104370914B (zh) 作为蛋白酶c抑制剂的3-酰氨基-吡咯并[3,4-c]吡唑-5(1h,4h,6h)甲醛衍生物
EP0258755B1 (fr) Alpha-alkyl-4-amino-3-quinoléine-méthanols et 1-(4-aralkylamino-3-quinolyl)alkanones, un procédé pour leur synthèse et leur utilisation comme médicaments
DE60218037T2 (de) Neue indolderivate mit affinität zum 5-ht6-rezeptor
EP0482939A1 (fr) Dérive d'isoquinolinone
JP3238397B2 (ja) 新規のスルホニル化合物
CS223977B2 (en) Method of preparation of the chinazoline derivatives
JPH0344388A (ja) ヘテロアリールピペラジン抗精神病薬
CH674368A5 (fr)
WO1989005803A1 (fr) Derives de 3,4-dihydro-2h-1,3-benzoxazine et leur utilisation en medecine
FI66868B (fi) Foerfarande foer framstaellning av imidazo(1,2-a)kinoxalinmetanoler anvaendbara saosom laekemedel
JPS6230780A (ja) １，７−ナフチリジン誘導体及びこれを含有する薬剤
JPH01502757A (ja) 向精神薬二環イミド類
JPS60214778A (ja) Ν置換３，４−ジヒドロピリミジン誘導体ならびにその製造法および用途
JPH01294670A (ja) ２−（ピペラジニル）−２−オキソエチレン−置換フラボノイド誘導体、その製法およびそれを含有する医薬組成物
JP2001503048A (ja) ２―メトキシフェニルピペラジン誘導体
JP2519734B2 (ja) 新規置換ピリド〔２，３−ｂ〕〔１，４〕ベンゾジアゼピン−６−オン，その製法及びその化合物を含む医薬
US4868190A (en) N-pyridinyl-9H-carbazol-9-amines
JPH0674266B2 (ja) ２，３―ジヒドロ―１―（ピリジニルアミノ）―インドールおよびその製造法
JP3117183B2 (ja) ５，６−ジヒドロ−４Ｈ−イミダゾ〔４，５，１−ｉｊ〕キノリン類、その製造方法、それを含む鎮痛剤および中間体化合物
JPS62281860A (ja) アルキレンアミノアルキレン　ヘテロ原子基を有するジヒドロ−３，５−ジカルボキシレ−ト
JP2009518383A (ja) 新規のシステインプロテアーゼ阻害剤、その薬剤組成物および治療のためのその使用
JPH0273015A (ja) 置換３，４‐ジヒドロ‐２ｈ‐ベンゾピラン類の肺の閉鎖性機能障害および／または輸出尿路の障害の治療薬としての使用
KR880001281B1 (ko) 9,10-치환된 2-메시틸이미노-3-알킬-3,4,6,7-테트라하이드로-2H-피리미도(6,1-a)이소퀴놀린-4-온의 제조방법
EP1914235A1 (fr) Dérivés chirales tetra-hydro beta-carbolines en tant qu'agents antiparasitaires
TW206230B (fr)

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): CH DE FR GB NL SE