GB2031410A - New derivatives of 1,3- benzoxazine-2,4-dione, their preparation and their application as medicaments - Google Patents
New derivatives of 1,3- benzoxazine-2,4-dione, their preparation and their application as medicaments Download PDFInfo
- Publication number
- GB2031410A GB2031410A GB7929266A GB7929266A GB2031410A GB 2031410 A GB2031410 A GB 2031410A GB 7929266 A GB7929266 A GB 7929266A GB 7929266 A GB7929266 A GB 7929266A GB 2031410 A GB2031410 A GB 2031410A
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- United Kingdom
- Prior art keywords
- benzoxazine
- dione
- chloro
- derivative
- hydrogen
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- 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]
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (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)
Abstract
The invention concerns 1,3- benzoxazine-2,4-dione derivatives of the formula <IMAGE> in which R represents an alkyl radical, an ortho-phenoxy-phenyl, ortho- thiophenoxy-phenyl, a benzyl, furfuryl or 2-pyridyl group; R' represents a hydrogen, chlorine, or bromine atom or a methoxy radical; R'' represents a hydrogen or chlorine atom or a methyl radical; and R''' represents a hydrogen, chlorine or bromine atom. R preferably represents a C1 to C4 alkyl radical. The derivatives of the invention have pharmacological (e.g. analgesic and anti-inflammatory) activity and may be administered in tablet, capsule, suppository and the like forms. Methods for the preparation of these derivatives are disclosed.
Description
SPECIFICATION
New derivatives of 1 ,3-benzoxazine-2,4-dione, their preparation and their application as medicaments
The present invention provides new derivatives of 1 ,3-benzoxazine-2, 4-dione, their preparation and their application as medicaments.
The new derivatives of the present invention, have with the general formula I
in which R represents an alkyl radical, especially a lower alkyl radical preferably with C, to C4, an orthophenoxy-phenyl, ortho-thiophenoxy-phenyl, a benzyl, furfuryl or a 2-pyridyl group;
R' represents a hydrogen, chlorine, or bromine atom or a methoxyl radical;
R" represents a hydrogen or chlorine atom or a methyl radial; and
R"' represents a hydrogen, chlorine or bromine atom.
The derivatives of general formula I have proved to possess valuable pharmacological properties.
The present invention therefore also relates to the application of these compounds as medicaments as well as to pharmaceutical compositions containing them as active ingredient.
The present invention also relates to the preparation of derivatives of general formula I. According to the invention, these derivatives of general formula I are obtained: a) by reaction of a derivative of salicylamide of general formula II
in which R, R', R" and R"'have the meanings indicated in connection with general formula I, with ethyl chlorocarbonate; or b) by reaction of a derivative of salicylic acid of general formula Ill
in which R', R" and R"' have the meaning indicated in connection with general formula I, with an isocyanate of general formula IV O=C=N-R (V) in which R has the meaning given in connection with general formula
By way of simple non-limiting examples, the preparation of a few derivatives of general formula I will hereinafter be described in more detail.
EXAMPLE 1
Preparation of 6-chloro-3-methyl- 1, 3-benzoxazine-2, 4-dione
37 ml (0.375 mole) of ethyl chlorocarbonate is added slowly (1/2 hour) to a solution of 18.6 g (0.1 mole) of 5-chloro-N-methylsalicylamide in pyridine. It is allowed to reflux for 7 hours, allowed to cool, is diluted with water, filtered and washed with distilled water. It is recrystallised from chloroform, washed with methanol at 5"C and 6-chloro-3-methyl-1, 3-benzoxazine-2, 4-dione with melting point 151-1 530C (see Table I) is obtained.
EXAMPLE 2
Preparation of 6-bromo-3-methyl- 1, 3-benzoxazine-2, 4-dione
7.5 ml (0.12 mole) of methyl isocyanate and 5 ml of triethylamine are added to a solution of 21.7 g (0.1 mole) of 5-bromosalicylic acid in 1 50 ml of benzene.
The mixture is stirred for 1 hour at ambient temperature and then allowed to reflux for 6 hours. It is evaporated to dryness, recrystallised from methanol and 6-bromo-3-methyl-1 ,3-benzoxazine-2,4-dione with melting point 1 860C (see Table I) is obtained.
EXAMPLES 3 TO 17
By operating as described in Examples 1 and 2 various derivatives were obtained, a number of the physio-chemical constants of which, such as the crystallisation- solvents, the melting points and the characteristic bands of the infra-red spectrum are indicated in Table I hereinafter.
TABLE I
Crystaillsa
Ex. Meiting tion Yleld IR No. R R' R'' R''' Point Solvent % (cm-1) C H Cl Br N 1 CH3 Cl H H 151-3 CHCl3 93 1300, 1350 Calc. 51,12 2,86 16,76 - 6,63 1690, 1770 Found 51,20 2,79 16,70 6,57 2 CH3 Br H H 186 CH3OH 19 1300, 1350 Calc. 42,23 2,36 - 31,14 5,47 1690, 1750 Found 42,15 2,41 31,27 5,32 3 CH2CH2CH3 Cl H H 118 CH2OH 52 1340 Calc. 55,17 4,21 14,80 - 5,85 1700, 1700 Found 55,25 4,15 14,73 5,97 4 CH(CH3)2 Cl H H 187-9 CH3OH 24 1330 Calc. 55,17 4,21 14,80 - 5,85 1700, 1770 Found 55,08 4,32 14,88 5,80 5 CH2CH2CH2CH3 Cl H H 103 CH3CH2OH 12 1300 Calc. 56,87 4,75 14,00 - 5,52 1700, 1770 Found 56,79 4,81 13,92 5,46 6 (CH2)15CH3 Cl H H 97 CH3COCH3 67 1350 Calc. 68,31 8,60 8,40 - 3,32 1700, 1770 Found 68,42 8,58 8,35 3,25 7 # Cl H H 152-5 CH3OH 42 1340 Calc. 62,60 3,51 12,33 - 4,87 1710, 1770 Found 62.55 3,57 12,28 4,97 8 # Cl H H 178-80 EtOH/Me2CO 46 1320 Calc. 56,27 2,90 12,77 - 5,05 1700, 1770 Found 58,14 2,87 12,69 4,98 9 # Cl H H 167 EtOH 70 1360 Calc. 65,73 3,30 9,70 - 3,83 1710, 1770 Found 65,81 3,34 9,77 3,95 TABLE I (continued)
Crystaillsa- ANALYSIS Ex. Meiting tion Yleld IR No. R R' R'' R''' Point Solvent % (cm-1) C H Cl Br N 10 # Cl H H 150 EtOH 98 1360 Calc. 62,90 3,17 9,29 - 3,67 1710, 1770 Found 63,02 3,09 9,34 3,80 11 CH3 H Cl H 192-4 CH3OH 10 1300, 1360 Calc. 51,11 2,86 16,78 - 6,62 1690, 1760 Found 50,98 2,93 16,89 6,63 12 CH2CH3 Cl H H 120-2 C Cl4 51 1340, 1350 Calc. 53,27 3,58 15,72 - 6,22 1700, 1770 Found 53,15 3,63 15,74 6,15 13 CH3 Cl H Cl 159-63 AcoEt 6 1300, 1360 Calc. 43,94 2,05 28,82 - 5,69 1690, 1770 Found 44,05 1,98 28,91 5,75 14 CH2CH2CH2CH3 Cl H Cl 106-8 CH3OH 46 1340 Calc. 50,00 3,85 24,61 - 4,86 1700, 1770 Found 49,87 3,91 24,57 4,79 15 CH2CH2CH2CH3 Br H Br 139 EtOH 38 1350 Calc. 38,23 2,94 - 42,39 3,72 1690, 1770 Found 38,32 3,01 42,53 3,77 16 CH3 CH3O H H 138-40 CH3OH/H2O 23 1300, 1355 Calc. 58,02 4,38 - - 6,77 1690, 1760 Found 57,91 4,42 6,85 17 CH3 H CH3 H 164 CH3OH 12 1300, 1370 Calc. 82,89 4,75 - - 7,33 1690, 1760 Found 62,97 4,70 7,40 Analgesic activity
The analgesic activity of the derivatives of general formula I has been determined using male mice of weight between 20 and 25 g. The product to be tested is administered orally in suspension in 5 % gum arabic by means of an oesophageal probe. The volume of the solution administered is 25 ml/kg and the concentration of the tested product is changed according to the dose administered.
Pain is caused in the animals by an intraperitoneal injection of 0.2 ml/20g solution of acetylcholine bromide with a concentration of 0.32 ml/ml. Five minutes before the administration of the tested product, the acetylcholine is injected into a batch of 5 mice. The product to be tested is then administered and the injection of acetylcholine is administered again after 20, 40, 80, 120 and 160 minutes. The number of contortions per injection of acetylcholine is always counted for 5 minutes.
The analgesic activity is calculated by means of the following formula:
It = 100 -(Nt/No). 100 = 100 (1 -Nt/No) where
It = inhibition of the pain after t minutes
No = number of contortions before the administration of the product
Nt = number of contortions after t minutes from the administration of the product.
Several doses of each product are administered so that the fifty per cent analgesic dose (AD--50) can be determined.
With each of these doses It is calculated for times of 20, 40, 80, 120 and 1 60 minutes. The mean of these five values of It for each dose is taken as the analgesic effect. The analgesic effects are represented graphically as a function of the logarithm of the corresponding dose.
From this curve the analgesic dose fifty, that is to say, the dose which produces a fifty per cent analgesic effect, is obtained.
By way of example, the results obtained for a few derivatives of formula I according to the invention have been indicated in Table II hereinafter.
Acute toxicity
The acute toxicity is determined orally with mice of 20 to 25 g weight, by using batches of 6 animals. Several doses in geometric progression are administered. The time of observation is 72 hours.
The fifty per cent lethal dose (LD-50) is calculated graphically by means of logarithmic-probabilistic paper.
By way of example, the results obtained for a few derivatives of formula I according to the invention are indicated in Table II hereinafter.
TABLE
Doses in mg/kg Example No. Deri vati ve AD-50 LD-50 1 6-chloro-3-methyl-1,3 benzoxazine-2,4-dione 30 233 2 6-bromo-3-methyl-1,3- benzoxazi ne-2,4-dione 90 717 3 6-chloro-3-propyl-1,3 benzoxazine-2,4-dione 240 < 650 8 6-chloro-3-furfuryl-1 3- ben zoxazine2,4-di one 280 > 550 9 6-chloro-3-(O-phenoxyphenyl) 1,3-benzoxazine-2,4-dione 675 > 750 10 6-chloro-3-(O-thiophenoxy-phenyl)- 1,3-benzoxazi ne-2,4-di one 650 > 1500 12 6-chloro-3-ethyl-1,3 benzoxazine-2,4-dione 172 > 250 Anti-inflammatory activity
The anti-inflammatory activity in the male rat of Sprague-Dawley stock is determined. An oedema is caused in the paw by subplantar injection of a 1 % solution of carragheenin. The volume of the paw is measured before the oral administration of the product after two and five hours with a plethysmometer.
The anti-inflammatory activity is calculated with respect to a reference batch. By way of example, the results obtained for the derivative of example I are indictated in Table Ill.
TABLE lil
7 Anti-inf I amrnatory Activity Dose Example Derivative (mg/kg) 2 hours 5 hours 6-ch 1 oro-3-methy 1- 1 1,3-benzoxazine- 100 26% 30% 2,4-dione Taking into account their good pharmacodynamic properties, the derivatives of general formula I are hence capable of being used as veterinary and/or human medicine, as analgesic, antipyretic and anti-inflammatory agents.
Pharmaceutical compositions which contain, according to the invention, besides an acceptable pharmaceutical support, at least one derivative of general formula I have a very large field of therapeutic application and can be utilised especially in traumatology, surgery, rheumatology, odonstostomatology, oto-rhino-laryngology, pneumology, cardiology, gynaecology and urology. These pharmaceutical compositions will be, for example, utilised for the treatment of various manifestations of pain, headaches, migraines, toothache, neuralgias, menstrual pains, inflammatory rheumatisms, arthritis pains, feverish states, colds, influenzas and seasonal infections.
In human therapy, the dose proposed for the derivatives of the present invention is approximately between 1 00 and 300 mg/day, administered for example in the form of tablets, capsules or suppositories.
Hereinafter, by way of example, three particular gallenic forms of the derivatives, the objects of the present invention, will be indicated.
Example of formula per tablet 6-chloro-3-methyl-l ,3-benzoxazine-2, 4-dione 100 mg Avicel pH-1 02 100 mg
Primojel 10 mg Aerosil-200 1 mg
Magnesium stearate 2 mg
Tablet weight 213 mg
Example of formula per capsule 6-chloro-3-methyl-1, 3-benzoxazine-2, 4-dione 100 mg
Lactose 75 mg
Avicel pH-1 02 25 mg Aerosil-200 1 mg
Magnesium stearate 2 mg
Capsule weight 203 mg
Example of formula per suppository 6-chloro3-methyi-l, 3-benzoxazine-2, 4-dione 0.2 g
Monolene 1.8 g
Suppository weight 2.0 g
Claims (17)
1. A derivative of 1 ,3-benzoxazine-2,4-dione of the general formula
in which R represents an alkyl radical, an ortho-phenox-)/-phenyl, ortho-thiophenoxy-phenyl, a benzyl, furfuryl or 2-pyridyl group; R' represents a hydrogen, chlorine, or bromine atom or a methoxy radical; R" represents a hydrogen or chlorine atom or a methyl radical; and R"' represents a hydrogen, chlorine or bromine atom.
2. A derivative as claimed in claim 1 wherein R represents a lower alkyl radical.
3. A derivative as claimed in claim 1 wherein R represents an alkyl radical with 1 to 4 carbon atoms.
4. 6-chloro-3-methyl- 1, 3-benzoxazine-2, 4-dione.
5. 6-chloro-3-ethyl-1, 3-benzoxazine-2, 4-dione.
6. 6-chloro-3-propyl-1, 3-benzoxazine-2, 4-dione.
7. 6-chloro-3-furfuryl-1 , 3-benzoxazine-2, 4-dione.
8. 6-chloro-3-(o-phenoxyphenyl)-1, 3-benzoxazine-2, 4-dione.
9. 6-chloro-3-(o-thiophenoxylphenyl)-1, 3-benzoxazine-2, 4-dione.
10. 6-bromo-3-methyl-1, 3-benzoxazine-2, 4-dione.
11. A method of preparation of a derivative as claimed in claim 1, wherein a derivative of salicylamide of the general formula
in which R, R', R" and R"' have the meaning indicated in claim 1 is-reacted with ethyl chlorocarbonate.
1 2. A method of preparation of a derivative as claimed in claim 1, wherein a derivative of salicylic acid of the general formual
in which R', R" and R"' have the meaning indicated in claim 1, is reacted with an isocyanate of general formula O=C=N-B in which R has the meaning given in claim 1.
13. A method as claimed in claim 14, conducted substantially as described in Example 1.
14. A method as claimed in claim 15, conducted substantially as described in Example 2.
1 5. A pharmaceutical composition comprising a compound as claimed in any one of claims 1 to 13 together with a pharmaceutically acceptable carrier.
1 6. A pharmaceutical composition as claimed in claim 1 9 in the form of a tablet, capsule or suppository.
17. A pharmaceutical composition as claimed in claim 19 substantially as described in the
Examples herein.
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 (2)
| Publication Number | Publication Date |
|---|---|
| GB2031410A true GB2031410A (en) | 1980-04-23 |
| GB2031410B GB2031410B (en) | 1982-12-01 |
Family
ID=9212085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB7929266A Expired GB2031410B (en) | 1978-08-25 | 1979-08-22 | Derivatives of 1,3 benzoxazine 2,4 dione,their preparation and their application as medicants |
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) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003103656A1 (en) * | 2002-06-06 | 2003-12-18 | 株式会社医薬分子設計研究所 | O-substituted hydroxyaryl derivatives |
| US7700655B2 (en) | 2002-06-06 | 2010-04-20 | Institute Of Medicinal Molecular Design, Inc. | Antiallergic agents |
| US8097759B2 (en) | 2000-12-18 | 2012-01-17 | Institute Of Medicinal Molecular Design, Inc. | Inflammatory cytokine release inhibitor |
| CN108658887A (en) * | 2018-06-20 | 2018-10-16 | 中南大学 | Benzo [d] [- 2,4 (1H)-derovatives of 1,3] oxazines and its preparation method and use |
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 GB GB7929266A patent/GB2031410B/en not_active Expired
- 1979-08-22 HU HU79PO694A patent/HU182916B/en not_active IP Right Cessation
- 1979-08-22 PL PL1979217893A patent/PL116771B1/en unknown
- 1979-08-22 CA CA334,287A patent/CA1128511A/en not_active Expired
- 1979-08-22 GR GR52886A patent/GR69619B/el unknown
- 1979-08-22 BG BG044725A patent/BG30929A3/en unknown
- 1979-08-23 AR AR277829A patent/AR222494A1/en active
- 1979-08-23 PT PT70107A patent/PT70107A/en unknown
- 1979-08-23 IL IL58096A patent/IL58096A/en not_active IP Right Cessation
- 1979-08-23 SU SU792804596A patent/SU797576A3/en active
- 1979-08-23 BE BE0/196852A patent/BE878395A/en not_active IP Right Cessation
- 1979-08-23 YU YU2073/79A patent/YU40849B/en unknown
- 1979-08-23 DE DE19792934166 patent/DE2934166A1/en not_active Ceased
- 1979-08-23 JP JP10764779A patent/JPS5533484A/en active Pending
- 1979-08-23 FI FI792632A patent/FI68818C/en not_active IP Right Cessation
- 1979-08-23 AT AT0568379A patent/AT373591B/en not_active IP Right Cessation
- 1979-08-24 SE SE7907067A patent/SE446865B/en not_active IP Right Cessation
- 1979-08-24 NL NL7906408A patent/NL7906408A/en not_active Application Discontinuation
- 1979-08-24 CH CH773579A patent/CH643548A5/en not_active IP Right Cessation
- 1979-08-24 CS CS795769A patent/CS208131B2/en unknown
- 1979-08-27 EG EG520/79A patent/EG14355A/en active
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8097759B2 (en) | 2000-12-18 | 2012-01-17 | Institute Of Medicinal Molecular Design, Inc. | Inflammatory cytokine release inhibitor |
| US8263657B2 (en) | 2000-12-18 | 2012-09-11 | Institute Of Medicinal Molecular Design, Inc. | Inhibitors against the production and release of inflammatory cytokines |
| WO2003103656A1 (en) * | 2002-06-06 | 2003-12-18 | 株式会社医薬分子設計研究所 | O-substituted hydroxyaryl derivatives |
| EA009051B1 (en) * | 2002-06-06 | 2007-10-26 | Инститьют Оф Медисинал Молекьюлар Дизайн. Инк. | O-substituted hydroxyaryl derivatives |
| AU2003242118B2 (en) * | 2002-06-06 | 2008-09-11 | Institute Of Medicinal Molecular Design, Inc | O-substituted hydroxyaryl derivatives |
| US7626042B2 (en) | 2002-06-06 | 2009-12-01 | Institute Of Medicinal Molecular Design, Inc. | O-substituted hydroxyaryl derivatives |
| US7700655B2 (en) | 2002-06-06 | 2010-04-20 | Institute Of Medicinal Molecular Design, Inc. | Antiallergic agents |
| CN108658887A (en) * | 2018-06-20 | 2018-10-16 | 中南大学 | Benzo [d] [- 2,4 (1H)-derovatives of 1,3] oxazines and its preparation method and use |
| CN108658887B (en) * | 2018-06-20 | 2022-04-05 | 中南大学 | Benzo [ d ] [1,3] oxazine-2, 4(1H) -diketone derivative and synthetic method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| AT373591B (en) | 1984-02-10 |
| CA1128511A (en) | 1982-07-27 |
| SE7907067L (en) | 1980-02-26 |
| NL7906408A (en) | 1980-02-27 |
| FR2434158B1 (en) | 1985-05-03 |
| CH643548A5 (en) | 1984-06-15 |
| PL217893A1 (en) | 1980-04-21 |
| PL116771B1 (en) | 1981-06-30 |
| FI792632A (en) | 1980-02-26 |
| FR2434158A1 (en) | 1980-03-21 |
| YU40849B (en) | 1986-06-30 |
| IL58096A (en) | 1982-12-31 |
| BE878395A (en) | 1980-02-25 |
| AR222494A1 (en) | 1981-05-29 |
| GB2031410B (en) | 1982-12-01 |
| GR69619B (en) | 1982-07-06 |
| SU797576A3 (en) | 1981-01-15 |
| JPS5533484A (en) | 1980-03-08 |
| ATA568379A (en) | 1983-06-15 |
| RO78156A (en) | 1982-02-01 |
| SE446865B (en) | 1986-10-13 |
| EG14355A (en) | 1983-12-31 |
| BG30929A3 (en) | 1981-09-15 |
| PT70107A (en) | 1979-09-01 |
| DD145534A5 (en) | 1980-12-17 |
| HU182916B (en) | 1984-03-28 |
| CS208131B2 (en) | 1981-08-31 |
| YU207379A (en) | 1983-02-28 |
| FI68818C (en) | 1985-11-11 |
| ES481856A1 (en) | 1980-02-16 |
| DE2934166A1 (en) | 1980-02-28 |
| FI68818B (en) | 1985-07-31 |
| IL58096A0 (en) | 1979-12-30 |
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| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19940822 |