CS208131B2 - Method of making the new derivatives of the 1,3-benzoxazine-2,4-dione - Google Patents
Method of making the new derivatives of the 1,3-benzoxazine-2,4-dione Download PDFInfo
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- CS208131B2 CS208131B2 CS795769A CS576979A CS208131B2 CS 208131 B2 CS208131 B2 CS 208131B2 CS 795769 A CS795769 A CS 795769A CS 576979 A CS576979 A CS 576979A CS 208131 B2 CS208131 B2 CS 208131B2
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- dione
- benzoxazine
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- OAYRYNVEFFWSHK-UHFFFAOYSA-N carsalam Chemical compound C1=CC=C2OC(=O)NC(=O)C2=C1 OAYRYNVEFFWSHK-UHFFFAOYSA-N 0.000 title claims description 4
- 238000004519 manufacturing process Methods 0.000 title 1
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- -1 o-phenoxyphenyl Chemical group 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical class NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 1
- 230000000202 analgesic effect Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 7
- GBNWQQUVAPTWKO-UHFFFAOYSA-N 6-chloro-3-methyl-1,3-benzoxazine-2,4-dione Chemical compound C1=C(Cl)C=C2C(=O)N(C)C(=O)OC2=C1 GBNWQQUVAPTWKO-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 210000003815 abdominal wall Anatomy 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 235000012431 wafers Nutrition 0.000 description 3
- 229920003084 Avicel® PH-102 Polymers 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- YKYIFUROKBDHCY-ONEGZZNKSA-N (e)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one Chemical group CCO\C=C\C(=O)C(F)(F)F YKYIFUROKBDHCY-ONEGZZNKSA-N 0.000 description 1
- GMFBXDUNANTIIL-UHFFFAOYSA-N 5-chloro-2-hydroxy-n-methylbenzamide Chemical compound CNC(=O)C1=CC(Cl)=CC=C1O GMFBXDUNANTIIL-UHFFFAOYSA-N 0.000 description 1
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 229920003110 Primojel Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- ZEHGKSPCAMLJDC-UHFFFAOYSA-M acetylcholine bromide Chemical compound [Br-].CC(=O)OCC[N+](C)(C)C ZEHGKSPCAMLJDC-UHFFFAOYSA-M 0.000 description 1
- 229940080018 acetylcholine injection Drugs 0.000 description 1
- 231100000460 acute oral toxicity Toxicity 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 229940090044 injection Drugs 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
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
- C07D265/24—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in positions 2 and 4
- C07D265/26—Two oxygen atoms, e.g. isatoic anhydride
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Pain & Pain Management (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Description
(54) Způsob výroby nových derivátů 1,3-benzoxazin-2,4-dionu(54) A process for the preparation of new 1,3-benzoxazine-2,4-dione derivatives
Vyiález se týká způsobu výroby nových derivátů 1,3-benzoxazin-2,4-dionu obecného vzorce IThe present invention relates to a process for the preparation of novel 1,3-benzoxazine-2,4-dione derivatives of the general formula I
(I) ve kterém ~(I) in which ~
R značí alkylový zbytek s 1 až 4 atomy uhlíku, skupinu o-fenoxyfenylovou, o-thiofenoxyfenylovou, benzylovou, furfurylovou nebo 2-pyridylovou;R is C1-C4alkyl, o-phenoxyphenyl, o-thiophenoxyphenyl, benzyl, furfuryl or 2-pyridyl;
R” značí atom vodíku, chloru, bromu nebo metho:xylový zbytek;R 'represents a hydrogen, chlorine, bromine or methoxyl radical;
R značí atom vodíku, chloru nebo methylový zbytek;R is hydrogen, chlorine or methyl;
R' značí atom vodíku, chloru nebo bromu.R 'represents a hydrogen, chlorine or bromine atom.
Deriváty obecného vzorce I mají cenné farmakologické vlastnosti.The derivatives of the formula I have valuable pharmacological properties.
Podle vynálezu se deriváty obecného vzorce I získají reakcí derivátu salicylamidu obecného vzorce IIAccording to the invention, the derivatives of the formula I are obtained by reaction of a salicylamide derivative of the formula II
(II) ve kterém R, R*, R**, R*, mají stejné významy jako v obecném vzorci I, s chlormravenČanem ethylnatým.(II) wherein R, R *, R **, R *, have the same meanings as in Formula I, with ethyl chloroformate.
Níže je ve formě příkladů podrobné popsána příprava některých derivátů obecného vzorce I, avěak tyto příklady vynález nijak neomezují.DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The preparation of certain derivatives of formula (I) is described in detail below by way of examples, but these examples do not limit the invention in any way.
PřikladlHe did
Příprava 6-chlor-3-methyl-1,3-benzoxazin-2,4-dionuPreparation of 6-chloro-3-methyl-1,3-benzoxazine-2,4-dione
К roztoku 18,6 g (0,1 mol) 5-chlor-N-methylsalicylamidu v pyridinu se pomalu (během půl hodiny) přidá 37 ml (0,375 mol) chlormravenčanu ethylnatého. Směs se vaří 7 hodin pod zpětným chladičem, nechá se zchladnout, zředí se vodou, odfiltruje a promyje destilovanou vodou. Rekrystaluje se z chloroformu, promyje se methanolem ochlazeným na 5 °C a získá se 6-chlor-3-methyl-1,3-benzoxazin-2,4-dion o teplotě tání 151 až 153 °C (viz tabulka I)·To a solution of 18.6 g (0.1 mol) of 5-chloro-N-methylsalicylamide in pyridine was slowly added (over half an hour) 37 ml (0.375 mol) of ethyl chloroformate. The mixture was refluxed for 7 hours, allowed to cool, diluted with water, filtered and washed with distilled water. Recrystallized from chloroform, washed with methanol cooled to 5 ° C to give 6-chloro-3-methyl-1,3-benzoxazine-2,4-dione, m.p. 151-153 ° C (see Table I).
Příklady 2 až 17Examples 2 to 17
Analogickým postupem podle příkladu 1 je možno například získat deriváty, jejichž některé fyzikálně-chemické konstanty, jako rozpouštědla pro krystalizaci, teploty tání, charakteristické pásy IČ-spektra jsou uvedeny v tabulce I.Analogous to Example 1, for example, derivatives can be obtained whose physicochemical constants, such as solvents for crystallization, melting points, and characteristic IR bands are given in Table I.
cccc
oO
C— b40 \oC— b40 \ o
м- ь— см on r>м- ь— см on r>
o on o u>o he o u>
b OO 00 o oj o in o 04 M co n oo t- o\b OO 00 o o o o o o 04 M co n oo t- o \
ОП OJ t— 40OJ t - 40
Ob- 04 MC— b- CM СП04- MC- b- CM СП
OO 04 CM Mb- 00 c- cMM M- MOO 04 CM Mb-00 c-cMM M-M
M· on 00 O0Man · 00 O0
OJ OJ CM CMOJ OJ CM CM
04 04 0404
40 IA LA40 IA LA
I I Λ4 '>>>O) Φ РП 04 OJ M ř> «μ >« 04 — ia cmI I Λ4 '>>> O) Φ РП 04 OJ M>> μ> 04 04 - ia cm
CMCM
Γ— OJOJ— OJ
MM
oO
O —About -
ďsďs
IAND
o к а I - pokračovánío к а I - continued
Analgetícké účinnostAnalgesic efficacy
Analgetícké účinnost derivátů obecného vzorce 1 byl© hodnocena na myších samcích ,o hmotnosti mezi 20 a 25 g« Zkoušené látka se podává v suspenzi v 5% roztoku arabské gumy perorálně žaludeční sondou. Objem podávaného roztoku je 25 ml/kg a koncentrace zkoušené látky se mění podle podávané dávky.The analgesic activity of the compounds of formula (1) was evaluated in male mice weighing between 20 and 25 g. The volume of solution administered is 25 ml / kg and the concentration of test substance varies according to the dose administered.
Bolest se u zvířat vyvolá pomocí intraperitoneální injekce 0,2 ml/20 g roztoku acetylcholinbromidu o koncentraci 0,32 mg/ml. Pět minut před podáním zkoušené látky se injikuje acetylcholin skupině 5 myší. Potom se podá zkoušená látka a znovu se injikuje acetylcholin v intervalech 20, 40, 80, 120 a 160 mi,nut. Počítá se vždy počet stahů břišní stěny vyvolaných injekcí acetylcholinu během 5 minut.Pain was induced in animals by intraperitoneal injection of 0.2 ml / 20 g of a 0.32 mg / ml acetylcholine bromide solution. Five minutes before administration of the test substance, acetylcholine is injected into a group of 5 mice. The test substance is then administered and acetylcholine is re-injected at 20, 40, 80, 120 and 160 ml intervals. The number of abdominal wall contractions induced by acetylcholine injection over 5 minutes is counted.
Analgetícké účinnost se vypočte pomocí tohoto vzorce:The analgesic potency is calculated using the following formula:
It » 100 - (Nt/No).100 = 100 (1-Nt/No) kde It = potlačení bolesti po t minutách,It »100 - (Nt / No) .100 = 100 (1-Nt / No) where It = pain relief after t minutes,
No - počet stahů břišní stěny před podáním zkoušené látky aNumber of abdominal wall contractions prior to administration of test substance, and
Nt = počet stahů břišní stěny po t minutách po podání zkoušené látky.Nt = number of abdominal wall contractions at t minutes after test substance administration.
Podává se více dávek každé látky, aby bylo možno stanovit dávku, která u 50 % zvířat vyvolá analgesii (DA-50).Multiple doses of each agent are administered to determine the dose that will cause analgesia (DA-50) in 50% of the animals.
Pro každou z těchto dávek se vypočte It v časovém intervalu 20, 40, 80, 120 a 160 minut. Jako analgetický účinek se bere průměr z pěti hodnot It pro každou dávku. Analgetícké účinky se znázorní graficky jako logaritmická funkce příslušné dávky.For each of these doses, It is calculated over a time interval of 20, 40, 80, 120 and 160 minutes. The mean of the five It values for each dose is taken as an analgesic effect. The analgesic effects are plotted as the logarithmic function of the dose in question.
Z této křivky se dostane analgetícké dávka padesát, tj. dávka která u 50 % zvířat vyvolá analgetický účinek.This curve yields an analgesic dose of fifty, i.e., a dose that produces an analgesic effect in 50% of the animals.
Jako příklady jsou v následující tabulce II uvedeny výsledky získané pro některé deriváty podle vynálezu obecného vzorce I.By way of example, the results obtained for certain derivatives of the invention of general formula I are given in Table II below.
Akutní toxicitaAcute toxicity
Akutní toxicita pro perorální podání se stanoví na myších o hmotnosti 20 až 25 g za použití skupin po 6 zvířatech. Podává se více dávek stoupajících v geometrické řadě. Doba pozorování je 72 hodin. Padesátiprocentní smrtná dávka (LD-50) se vypočte graficky pomocí logaritmicko-probitového papíru.Acute oral toxicity is determined in mice weighing 20-25 g using groups of 6 animals each. Multiple doses rising in a geometric series are administered. The observation period is 72 hours. The 50% death dose (LD-50) is calculated graphically using log-probit paper.
Jako příklady jsou uvedeny v tabulce II výsledky získané pro některé deriváty podle vynálezu obecného vzorce I.By way of example, Table II shows the results obtained for some of the derivatives of the invention of formula (I).
Tabulka IITable II
Protizánětlivá účinnostAnti-inflammatory activity
Protizánětlivá účinnost byla stcnovena na krysích samcích kmene Sprague-Dawley. Vyvolá se edem na pacce subplantární injekcí 1% roztoku cerrageninu. Měří se objem packy před perorálním podáním látky a po dvou a pěti hodinách pomocí pletýsmomeeru. Protizánět-Anti-inflammatory activity was assessed in male Sprague-Dawley rats. It is induced in the paw by subplantar injection of 1% cerragenine solution. The paw volume is measured before oral administration and after two and five hours using a plethome meter. Anti-inflammatory-
Na základě dobrých farmakodynamických vlastností jsou látky obecného vzorce I vhodná pro použití v hummáini meeicíně a/nebo veterinární meeicíně jako - analgeticky, antipyroticky a protizánětlivá účinná léčiva.Because of their good pharmacodynamic properties, the compounds of the formula I are suitable for use in hummus medicine and / or veterinary medicine as analgesic, antipyrotic and anti-inflammatory drugs.
Fa:rm^(^c^e^t^:Lcké přípravky které obsahují podle vynálezu, kromě farmaceuticky vhodného nosiče, nejméně jeden derivát obecného vzorce I, ob2í velmi ěiroké pole terapeutického použití a mohou být využity zejména v ti^E^um^aí^l^(^o^ii, chirurgii, reumaatlogii, odontostomatologii, oto-rhino-laryngooooii, pneiunollgii, kardiologii, gynekooogii a urologii. Tyto farmaceutické přípravky budou použity k léčení rozmanitých projevů bo].eeti, například bolestí hlavy, bdestí zubů, - nevuragií, οοη^™^^^ booeetí, reu^s^ttických zánětů, arthrotických bdeetí, horečnatých stavů, rým, chřipek a sezónních infekcí.Pharmaceutical compositions which contain, in addition to a pharmaceutically acceptable carrier, at least one derivative of the general formula I according to the invention have a very wide field of therapeutic use and can be used in particular in the pharmaceutical composition. Surgery, rheumatology, odontostomatology, oto-rhino-laryngooooii, pneumonia, cardiology, gynecology and urology. These pharmaceutical compositions will be used to treat a variety of manifestations of diabetes, such as headache, toothache. Nevuragia, οοη ^ ™ο^ boooooooooooooooooooooooooooooooooo booooooooooooooooooooooooooooooooooooooooooo reoo reooooooo reoo re re re re re re re re re re re re re re re re re re re re re re re re re re re re re re re re re re re re re re re re.
I I · I I ·
V humťámí terapii je navrhována dávka látek.podle vynálezu přibližně v rozmezí mezi 100 a 300 m/d, podaná například ve formě tablet, oplatek nebo čípků.In human therapy, a dose of the compounds of the invention of between about 100 and 300 m / d, for example in the form of tablets, wafers or suppositories, is suggested.
Níže jsou uvedeny jako příklady tři obecné ialenické formy derivátů, které jsou předmětem vynálezu.The three general ileic derivatives of the present invention are exemplified below.
Příklad složení tabletyTablet composition example
6-chlor-3-methyl-1,3-benzoxazin-2,4-dion 100mg mikrokrystalická, částečně depolymerizovaná celulóza (avicel pH-102) 100mg karboxymethylovaný Škrob (Primojel) 10mg koloidní kysličník křemičitý (Herosil-200) 1mg stearan hořečnatý 2mg6-chloro-3-methyl-1,3-benzoxazine-2,4-dione 100mg microcrystalline, partially depolymerized cellulose (avicel pH-102) 100mg carboxymethylated Starch (Primojel) 10mg colloidal silicon dioxide (Herosil-200) 1mg magnesium stearate 2mg
Hmotnost tablety 213mgWeight tablet 213mg
Příklad složení oplatkyExample of wafer composition
6-chlor-3-methyl-1,3-benzoxazin-2,4-dion 100 laktóza 75 mikrokrystalická, Částečně depolymerizovaná celulóza (Avicel pH-102) 25 koloidní kysličník křemičitý (Aerosil-200) 1 stearan hořečnatý __£6-chloro-3-methyl-1,3-benzoxazine-2,4-dione 100 lactose 75 microcrystalline, partially depolymerized cellulose (Avicel pH-102) 25 colloidal silicon dioxide (Aerosil-200) 1 magnesium stearate __ £
Hmotnost oplatky 203Weight of wafer 203
Příklad složení čípkuExample of suppository composition
6-chlor-3-methyl-1,3-benzoxazin-2,4-dion0,2 g polosyntetické triglyceridy přírodních mastných kyselin (Monolen)1.8 g6-chloro-3-methyl-1,3-benzoxazine-2,4-dione 0.2 g semisynthetic natural fatty acid triglycerides (Monolen) 1.8 g
Hmotnost čípku2,0 gSuppository weight 2.0 g
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7824674A FR2434158A1 (en) | 1978-08-25 | 1978-08-25 | NOVEL 1,3-BENZOXAZINE-2,4-DIONE DERIVATIVES, THEIR PREPARATION AND THEIR APPLICATION AS MEDICAMENTS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS208131B2 true CS208131B2 (en) | 1981-08-31 |
Family
ID=9212085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS795769A CS208131B2 (en) | 1978-08-25 | 1979-08-24 | Method of making the new derivatives of the 1,3-benzoxazine-2,4-dione |
Country Status (25)
| Country | Link |
|---|---|
| JP (1) | JPS5533484A (en) |
| AR (1) | AR222494A1 (en) |
| AT (1) | AT373591B (en) |
| BE (1) | BE878395A (en) |
| BG (1) | BG30929A3 (en) |
| CA (1) | CA1128511A (en) |
| CH (1) | CH643548A5 (en) |
| CS (1) | CS208131B2 (en) |
| DD (1) | DD145534A5 (en) |
| DE (1) | DE2934166A1 (en) |
| EG (1) | EG14355A (en) |
| ES (1) | ES481856A1 (en) |
| FI (1) | FI68818C (en) |
| FR (1) | FR2434158A1 (en) |
| GB (1) | GB2031410B (en) |
| GR (1) | GR69619B (en) |
| HU (1) | HU182916B (en) |
| IL (1) | IL58096A (en) |
| NL (1) | NL7906408A (en) |
| PL (1) | PL116771B1 (en) |
| PT (1) | PT70107A (en) |
| RO (1) | RO78156A (en) |
| SE (1) | SE446865B (en) |
| SU (1) | SU797576A3 (en) |
| YU (1) | YU40849B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101088557B1 (en) | 2000-12-18 | 2011-12-05 | 가부시키가이샤 이야쿠 분지 셋케이 겐쿠쇼 | Inflammatory Cytokine Production Free Inhibitor |
| CA2488363C (en) * | 2002-06-06 | 2011-01-04 | Institute Of Medicinal Molecular Design, Inc. | O-substituted hydroxyaryl derivatives |
| TW200402291A (en) | 2002-06-06 | 2004-02-16 | Inst Med Molecular Design Inc | Antiallergic |
| CN108658887B (en) * | 2018-06-20 | 2022-04-05 | 中南大学 | Benzo[d][1,3]oxazine-2,4(1H)-dione derivatives and their synthetic methods and uses |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2476559A (en) * | 1946-10-01 | 1949-07-19 | Gen Aniline & Film Corp | Oxazine diones |
| DE1153375B (en) * | 1960-05-25 | 1963-08-29 | Thomae Gmbh Dr K | Process for the preparation of benzoxazine- (1, 3) -dione- (2, 4) |
| GB1069367A (en) * | 1964-10-01 | 1967-05-17 | Aspro Nicholas Ltd | Improvements in or relating to the production of 1:3-benzoxazine-2:4-dione |
| CH459211A (en) * | 1965-01-25 | 1968-07-15 | Robapharm Ag | Process for the preparation of new basic derivatives of dihydro-1,3-benzoxazine-2,4-dione |
-
1978
- 1978-08-25 FR FR7824674A patent/FR2434158A1/en active Granted
-
1979
- 1979-06-06 ES ES481856A patent/ES481856A1/en not_active Expired
- 1979-08-21 DD DD79215096A patent/DD145534A5/en not_active IP Right Cessation
- 1979-08-22 RO RO7998518A patent/RO78156A/en unknown
- 1979-08-22 BG BG044725A patent/BG30929A3/en unknown
- 1979-08-22 GB GB7929266A patent/GB2031410B/en not_active Expired
- 1979-08-22 HU HU79PO694A patent/HU182916B/en not_active IP Right Cessation
- 1979-08-22 GR GR52886A patent/GR69619B/el unknown
- 1979-08-22 CA CA334,287A patent/CA1128511A/en not_active Expired
- 1979-08-22 PL PL1979217893A patent/PL116771B1/en unknown
- 1979-08-23 AR AR277829A patent/AR222494A1/en active
- 1979-08-23 DE DE19792934166 patent/DE2934166A1/en not_active Ceased
- 1979-08-23 FI FI792632A patent/FI68818C/en not_active IP Right Cessation
- 1979-08-23 PT PT70107A patent/PT70107A/en unknown
- 1979-08-23 YU YU2073/79A patent/YU40849B/en unknown
- 1979-08-23 BE BE0/196852A patent/BE878395A/en not_active IP Right Cessation
- 1979-08-23 SU SU792804596A patent/SU797576A3/en active
- 1979-08-23 AT AT0568379A patent/AT373591B/en not_active IP Right Cessation
- 1979-08-23 IL IL58096A patent/IL58096A/en not_active IP Right Cessation
- 1979-08-23 JP JP10764779A patent/JPS5533484A/en active Pending
- 1979-08-24 NL NL7906408A patent/NL7906408A/en not_active Application Discontinuation
- 1979-08-24 CS CS795769A patent/CS208131B2/en unknown
- 1979-08-24 CH CH773579A patent/CH643548A5/en not_active IP Right Cessation
- 1979-08-24 SE SE7907067A patent/SE446865B/en not_active IP Right Cessation
- 1979-08-27 EG EG520/79A patent/EG14355A/en active
Also Published As
| Publication number | Publication date |
|---|---|
| BE878395A (en) | 1980-02-25 |
| SE7907067L (en) | 1980-02-26 |
| ES481856A1 (en) | 1980-02-16 |
| FR2434158B1 (en) | 1985-05-03 |
| PL217893A1 (en) | 1980-04-21 |
| PL116771B1 (en) | 1981-06-30 |
| DE2934166A1 (en) | 1980-02-28 |
| IL58096A (en) | 1982-12-31 |
| AR222494A1 (en) | 1981-05-29 |
| RO78156A (en) | 1982-02-01 |
| FI68818B (en) | 1985-07-31 |
| FR2434158A1 (en) | 1980-03-21 |
| GB2031410A (en) | 1980-04-23 |
| FI792632A7 (en) | 1980-02-26 |
| FI68818C (en) | 1985-11-11 |
| NL7906408A (en) | 1980-02-27 |
| GB2031410B (en) | 1982-12-01 |
| DD145534A5 (en) | 1980-12-17 |
| JPS5533484A (en) | 1980-03-08 |
| SU797576A3 (en) | 1981-01-15 |
| IL58096A0 (en) | 1979-12-30 |
| AT373591B (en) | 1984-02-10 |
| GR69619B (en) | 1982-07-06 |
| PT70107A (en) | 1979-09-01 |
| HU182916B (en) | 1984-03-28 |
| SE446865B (en) | 1986-10-13 |
| ATA568379A (en) | 1983-06-15 |
| CH643548A5 (en) | 1984-06-15 |
| YU207379A (en) | 1983-02-28 |
| BG30929A3 (en) | 1981-09-15 |
| CA1128511A (en) | 1982-07-27 |
| YU40849B (en) | 1986-06-30 |
| EG14355A (en) | 1983-12-31 |
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