GB2063263A - A 1-isopropyl-4-phenyl-2(1H)- quinazolinone Derivative - Google Patents
A 1-isopropyl-4-phenyl-2(1H)- quinazolinone Derivative Download PDFInfo
- Publication number
- GB2063263A GB2063263A GB8036362A GB8036362A GB2063263A GB 2063263 A GB2063263 A GB 2063263A GB 8036362 A GB8036362 A GB 8036362A GB 8036362 A GB8036362 A GB 8036362A GB 2063263 A GB2063263 A GB 2063263A
- Authority
- GB
- United Kingdom
- Prior art keywords
- compound
- formula
- isopropyl
- phenyl
- pharmaceutical
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
- C07D239/82—Oxygen atoms with an aryl radical attached in position 4
-
- 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)
- 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)
Abstract
Compound of formula I, <IMAGE> is useful for treating phlogistic conditions and pain.i
Description
SPECIFICATION A 1 -lsopropyl-4Phenyl-2( 1 H)-Quinazol inone Derivative, Its Production and Pharmaceutical
Compositions Containing it
The present invention provides the compound of formula I,
namely 1 -isopropyl-4-(4'-fluorophenyl)-5-methyl 2(1 H)-quinazolinone.
The compound of formula I falls under the scope of DAS 1 805 501, but is not specifically disclosed therein. It has now been found that the compound of formula I possesses valuable pharmacological activity whilst at the same time only exhibiting the ulcerogenicity normally associated with compounds of this type to a very limited extent.
The invention also provides a process for the production of the compound of formula I, characterised by cyclising the compound of formula II,
with urea or a C,~5-alkyicarbamate in the presence of an aromatic acid.
The process may be effected in manner analogous to that described in DOS 2 753 970 and is conveniently carried out in the presence or absence of an inert organic solvent. Suitable temperatures lie between 120 and 1800 C, preferably 140 and 1600 C. Suitable aromatic acids include benzoic acid and o- or pmethylbenzoic acid. The aromatic acid is preferably employed in amount of at least 1 mol, preferably 3 to 6 mols per mol of 2aminobenzophenone derivative.
The compound of formula II may be prepared by reacting in liquid medium, a compound of formula Ill,
with acetone, a borohydride and an acid, or the reaction product of a borohydride and an acid.
This process can be effected in manner analogous to that described in DOS 2 701 888.
The compound of formula I exhibits pharmacological activity. In particular the compound exhibits antiphlogistic activity, as indicated in standard tests, for example by inhibition of oedema formation in the carrageen paw oedema test in rats on pto. administration of from 10 to 100 mg/kg animal body weight of the compound [Winter, Proc. Soc. Exp. Biol. Med.
111,544(1962)j.
The compound is therefore indicated for use as an antiphlogisic agent. For this use an indicated daily dosage is from about 100 to about 1000 mg, conveniently given in divided doses 2 to 4 times a day in unit dosage form containing from about 25 mg to about 500 mg or in sustained release form.
The compound of formula I exhibit further analgesic activity as indicated in standard tests.
For example, in one standard test an inhibition of the phenyl benzoquinone syndrome is observed in mice on p.o. administration of from 10 to 50 mg/kg animal body weight of the compound.
The compound is therefore indicated for use as an analgesic agent. For this use an indicated daily dosage is from about 30 to about 350 mg, conveniently administered in divided doses 2 to 4 times a day in unit dosage form containing from about 7.5 mg to about 175 mg or in sustained release form.
The compound of formula I has surprisingly a low propensity to produce gastric erosions, as indicated in standard tests. For example in one test rats starved overnight were administered the compound orally and sacrificed 6 hours later. The stomachs were examined for superficial erosions.
The dose-responsecurves were estimated using probit-analysis. The UDso was taken as the dose which induced petechial hemorrhages in 50% of the rats. The UD50 mg/kg p.o. is 91.1.
The present invention also provides a pharmaceutical composition comprising the compound of formula I in association with a pharmaceutical carrier or diluent. Such composition may be in the form of, for example, a solution or a tablet. The invention concerns in addition the use of the compound of formula I as a pharmaceutical in particular as an analgesic or antiphlogistic and in the treatment of the human or animal body by therapy.
In the following Example all temperatures are in degrees Centigrade.
Example 1 -Isopropyl-4-(4'-fluorophenyl)-5-methyl- 2(1 H)-quinazolinone a) 2-Amino-6-methyl-4'-fluorobenzophenone To a solution of 53.6 g m-toluidine in 160 ml
1,2-dichloroethane 64.8 g borontrichloride are added at 600 over a period of 1 hour. 121 g of 4fluorobenzonitrile in 40 ml dichloroethane and 73.4 g of aluminium chloride are then added at the same temperature. The mixture is heated for 4 hours under reflux and the resulting imine hydrolised to the ketone with hydrochloric acid.
The phases are separated at pH 3. The organic phase is evaporated and the residue dissolved in 360 ml ethanol. The solution is cooled to 0 and filtered off to remove unwanted 2-amino4methyl-4'-fluorobenzophenone. The filtrate is then concentrated, dissolved in 60 ml xylene and extracted with 10% aqueous hydrochloric acid.
After addition of aqueous sodium hydroxide the title compound is obtained as a brown oil.
b) 2-N-lsopropylamino-6-methyl-4'- fluorobenzophenone
To a solution of 50 g 2-amino-6-methyl-4'fluorobenzophenone in 250 ml acetone are added 44.8 g o-phthalic acid. The mixture is heated to 450 and 8.5 g of sodium borohydride added portionwise over a period of 1 hour. The temperature is then raised to 550 and maintained for 1 hour. The mixture is then cooled at 400, 140 ml of 20% aqueous sodium hydroxide is added and the phases separated. The water phase is extracted vvlth toluene. The combined acetone and toluene phases are concentrated and distilled in vacuo to give the title compound, b.p.
136/0.06 Torr.
C) I -lsopropyl-4-(4'-fluorophenyl)-5-methyl- 2!1 H)-quinazolinone A solution of 45.0 g 2-N-isopropylamino-6 rnethyl-4'-fluorobenzophenone in 60 ml of xylene is heated to 800. 88.5 g of benzoic acid and 34.0 g of methyl carbamate are added and the mixture is heated to 1 550 for 10 hours, during which time xylene-water is distilled off. The mixture is then cooled to 900, diluted with 170 ml xylene and washed with aqueous sodium hydroxide. The hot xylene solution is dehydrated and cooled to 0 to give the title compound, m.p. 183.5-184.5.
Claims (6)
1. A process for the production of the compound of formula
which comprises cyclising the compound of formula II
with urea or an C,,-alkylcarbamate in the presence of an aromatic acid.
2. Compound of formula I as defined in claim 1.
3. Compound of formula I for use as a pharmaceutical.
4. Compound of formula I for use as an antiphlogistic or analgesic agent.
5. A pharmaceutical composition which comprises the compound of formula I in association with a pharmaceutical carrier and/or diluent.
6. A method for treating phlogistic conditions and pain which comprises administering a therapeutically effective amount of the compound of formula I to a subject in need of such treatment.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1020179 | 1979-11-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB2063263A true GB2063263A (en) | 1981-06-03 |
Family
ID=4360522
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8036362A Withdrawn GB2063263A (en) | 1979-11-15 | 1980-11-12 | A 1-isopropyl-4-phenyl-2(1H)- quinazolinone Derivative |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPS5686173A (en) |
| DE (1) | DE3041678A1 (en) |
| FR (1) | FR2469407A1 (en) |
| GB (1) | GB2063263A (en) |
| IT (1) | IT8050159A0 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4645836A (en) * | 1983-09-12 | 1987-02-24 | Ortho Pharmaceutical Corporation | Process for the preparation of 6,7-dihydroxy-4-alkyl-2(1H) quinazolinone-1-propionic acids |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0223730D0 (en) * | 2002-10-11 | 2002-11-20 | Novartis Ag | Organic compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE792942A (en) * | 1972-03-09 | 1973-06-18 | Sandoz Sa | NEW DERIVATIVE OF QUINAZOLINONE, ITS PREPARATION AND APPLICATION IN THERAPEUTICS |
-
1980
- 1980-11-05 DE DE19803041678 patent/DE3041678A1/en not_active Withdrawn
- 1980-11-12 FR FR8024028A patent/FR2469407A1/en active Pending
- 1980-11-12 GB GB8036362A patent/GB2063263A/en not_active Withdrawn
- 1980-11-13 IT IT8050159A patent/IT8050159A0/en unknown
- 1980-11-14 JP JP16130680A patent/JPS5686173A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4645836A (en) * | 1983-09-12 | 1987-02-24 | Ortho Pharmaceutical Corporation | Process for the preparation of 6,7-dihydroxy-4-alkyl-2(1H) quinazolinone-1-propionic acids |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2469407A1 (en) | 1981-05-22 |
| JPS5686173A (en) | 1981-07-13 |
| DE3041678A1 (en) | 1981-05-27 |
| IT8050159A0 (en) | 1980-11-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4051141A (en) | Thieno[3,2-c]pyridine derivatives | |
| US4110337A (en) | Triazolobenzodiazepines | |
| IE44904B1 (en) | Aminophosphonous acids and processes for their preparation | |
| IE48436B1 (en) | Phenethanolamines,their formulations,preparation and use | |
| US4267190A (en) | Antiinflammatory 4,5-diaryl-α,α-bis(polyfluoromethyl)-1H-pyrrole-2-methanethiols | |
| CA1144551A (en) | Antiinflammatory 4,5-diaryl-a-(polyfluoroalkyl)-1h- pyrrole-2-methanamines | |
| US3709906A (en) | 2-alkyl-4,5-diphenylpyrrole derivatives | |
| GB2061274A (en) | 3-benzoyl-2-nitrophenylacetic acids metal salts amides and esters | |
| HU181147B (en) | Process for preparing substituted heterocyclin phenoxamines | |
| US3459767A (en) | Aminomethylindoles | |
| EP0061056A1 (en) | 5,6-Dimethylpyrrolo (2,3-b) pyridines, process for their preparation and their use as medicaments | |
| US3127401A (en) | Z-benzyl-j | |
| GB2063263A (en) | A 1-isopropyl-4-phenyl-2(1H)- quinazolinone Derivative | |
| Pataki et al. | Relative carcinogenicity of some diethylbenz [a] anthracenes | |
| US4198431A (en) | Alkyl N-(3-trifluoromethylphenyl)-anthranilate | |
| JPS61126082A (en) | Aminopyrrolidone derivative, its ester and its salt | |
| HU190710B (en) | Process for preparing 2-/4-piperazinyl/-4-phenyl-quinazoline derivatives | |
| US4143143A (en) | Substituted imidazo[5,1-a]isoquinolines | |
| US3153050A (en) | Spiro | |
| US4259335A (en) | 1-Methyl-4-piperidinol esters of 4-quinolinylamino benzoates and antiinflammatory and analgesic compositions and methods employing them | |
| HU184791B (en) | Process for preparing derivatives of tetrahydro-pyrid-4-yl-indole | |
| DE2462460A1 (en) | 2- SQUARE CLAMP ON (QUINOLYL- 4 ') - AMINO SQUARE BRACKET TO -BENZOIC ACID ESTERS, THEIR SALT WITH ACIDS, PROCESS FOR THEIR MANUFACTURING AND MEDICINAL PRODUCTS | |
| EP0058009A1 (en) | Novel benzanilide derivatives and pharmaceutical compositions containing them | |
| US3764688A (en) | 4,6-DIHYDRO-1,3-DIMETHYL-8-PHENYL-4-PROPARGYL-PYRAZOLO {8 4,3-e{9 {0 DIAZEPIN-5 (1H) ONE IN TREATING INFLAMMATION | |
| US4010161A (en) | Piperazinoethyl-N-(2,3-dimethyl-5-oxo-1-phenyl-3Δ-pyrazolin-4-yl)carbamates |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |