NO801843L - NEW CHINAZOLINE DERIVATIVES AND PHARMACEUTICAL PREPARATIONS - Google Patents
NEW CHINAZOLINE DERIVATIVES AND PHARMACEUTICAL PREPARATIONSInfo
- Publication number
- NO801843L NO801843L NO801843A NO801843A NO801843L NO 801843 L NO801843 L NO 801843L NO 801843 A NO801843 A NO 801843A NO 801843 A NO801843 A NO 801843A NO 801843 L NO801843 L NO 801843L
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- Prior art keywords
- formula
- compound
- compounds
- imidazo
- tautomers
- Prior art date
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Foreliggende oppfinnelse vedrører nye kinazolinderivater i D-form eller som racemater med formel The present invention relates to new quinazoline derivatives in D-form or as racemates with formula
• 1 • 1
hvori R er brom og R metyl eller klor, eller R me-- in which R is bromine and R methyl or chlorine, or R me--
2 2
toksy og R klor, toxin and R chlorine,
og deres tautomerer, samt salter av slike forbindelser med mineralsyrer. and their tautomers, as well as salts of such compounds with mineral acids.
Gruppen av forbindelser med formel I består av The group of compounds of formula I consists of
7-brom-l, 5-dihydro-3', 6-dimetyl-imidazo [2 ,1-b] kinazolin-2 (3H) - on 7-bromo-1,5-dihydro-3',6-dimethyl-imidazo[2,1-b]quinazolin-2(3H)-one
7-brom-6-klor-l,5-dihydro-3-metyl-imidazo[2,1-b]kinazolin-2(3H)-on og 7-bromo-6-chloro-1,5-dihydro-3-methyl-imidazo[2,1-b]quinazolin-2(3H)-one and
6-klor-l,5-dihydro-7-metoksy-3-metyl-imidazo[2,l-b]kinazolin-2(3H)-on. 6-chloro-1,5-dihydro-7-methoxy-3-methyl-imidazo[2,1-b]quinazolin-2(3H)-one.
Under gruppen av forbindelser med formel I er Among the group of compounds of formula I are
D, L-7-brom-l, 5-dlhydro-3., 6-dimetyl-imidazo [ 2 ,1-b] kinazolin-2(3H)-on og spesielt-D-7-brom-l,5-dihydro-3,6-dimetyl-imidazo[2,1-b]kinazolin-2(3H)-on D,L-7-bromo-1,5-dlhydro-3,6-dimethyl-imidazo[2,1-b]quinazolin-2(3H)-one and especially-D-7-bromo-1,5- dihydro-3,6-dimethyl-imidazo[2,1-b]quinazolin-2(3H)-one
og deres tautomerer samt salter av slike forbindelser med mineralsyrer foretrukket. and their tautomers as well as salts of such compounds with mineral acids preferred.
Oppfinnelsen vedrører videre fremgangsmåte véd fremstilling The invention further relates to the method of manufacture
av nevnte forbindelser samt farmasøytiske preparater på bas- of said compounds as well as pharmaceutical preparations based on
is av de nevnte forbindelser. ice of the aforementioned compounds.
Forbindelsene med formel I kan foreligge i forskjellige tautomere former. Oppfinnelsen er derfor ikke begrenset til forbindelser av de ovenfor viste med formel I, men omfatter også de. tautomerer, eksempelvis sådanne med formel The compounds of formula I can exist in various tautomeric forms. The invention is therefore not limited to compounds of those shown above with formula I, but also includes them. tautomers, for example those with formula
Forbindelsene med formel I og deres tautomerer, f.eks. la og Ib, kan videre foreligge i form av racemater éller i optisk aktiv form, hvorunder racematene og forbindelsene i D-form er gjenstand for oppfinnelsen. The compounds of formula I and their tautomers, e.g. la and Ib, can also exist in the form of racemates or in optically active form, whereby the racemates and compounds in D-form are the subject of the invention.
Eksempler på fysiologisk fordragelige salter med mineralsyrer er hydroklorider, hydrobromider, sulfater og fosfater. Examples of physiologically tolerable salts with mineral acids are hydrochlorides, hydrobromides, sulphates and phosphates.
Forbindelsene med formel I, deres tautomerer og salter av slike forbindelser med mineralsyrer kan ifølge oppfinnelsen fremstilles ved at man According to the invention, the compounds of formula I, their tautomers and salts of such compounds with mineral acids can be prepared by
a) bromerer en forbindelse med formel a) bromates a compound of formula
2] 2]
hvori R er metyl eller klor, wherein R is methyl or chlorine,
i 7-stilling, eller in 7 position, or
b) omsetter en forbindelse med formel b) reacts a compound of formula
123 123
hvori R og- R har ovenfor nevnte betydning og R er lavere-alkyl med bromcyan, eller in which R and - R have the above-mentioned meaning and R is lower alkyl with cyanogen bromide, or
c) behandler en forbindelse med formel c) processes a compound with formula
hvori R 1 -R 3 har ovenfor nevnte betydning, in which R 1 -R 3 have the above-mentioned meaning,
med ammoniakk, og with ammonia, and
isolerer en erholdt forbindelse med formel I eller en tauto- isolates an obtained compound of formula I or a tauto-
mer derav i denne form eller i form av et salt med en mineralsyre. more thereof in this form or in the form of a salt with a mineral acid.
Bromeringen av en forbindelse med formel II i 7-stilling utføres hensiktsmessig i eddiksyre ved ca. romtemperatur.' The bromination of a compound of formula II in the 7-position is suitably carried out in acetic acid at approx. room temperature.'
Omsetningen av en forbindelse med formel III med bromcyan utføres hensiktsmessig under oppvarmning i et løsningsmiddel så som en lavere alkanol, f.eks. etanol. Omsetningen av en forbindelse med formel IV med ammoniakk utføres hensiktsmessig under oppvarming i et løsningsmiddel så som en lavere alkanol, f.eks. etanol og vann. The reaction of a compound of formula III with cyanogen bromide is conveniently carried out under heating in a solvent such as a lower alkanol, e.g. ethanol. The reaction of a compound of formula IV with ammonia is conveniently carried out under heating in a solvent such as a lower alkanol, e.g. ethanol and water.
Forbindelsene med formlene II, III og IV tilhører en al-minnelig kjent giruppe av forbindelser og kan fremstilles analogt kjente forbindelser, f.eks. ifølge de metoder, som er beskrevet i DOS 2.832.138. The compounds with the formulas II, III and IV belong to a generally known group of compounds and can be prepared analogously to known compounds, e.g. according to the methods described in DOS 2,832,138.
Forbindelsene med formel l i D-form eller som racemater • deres tautomerer og. fysiologisk fordragelige salter av slike forbindelser med mineralsyrer skal finne anvendelse som legemidler. De hemmer blodplateaggregering og kan derfor anvendes for å forhindre tromboser. The compounds of formula I in D form or as racemates • their tautomers and. physiologically tolerable salts of such compounds with mineral acids shall find use as pharmaceuticals. They inhibit platelet aggregation and can therefore be used to prevent thrombosis.
Forbindelsene med formel I i D-form eller som racemater og deres tautomerer kan finne anvendelse som legemidler, f.eks. i form av farmasøytiske preparater, hvilke inneholder dem eller deres salter i blanding med et.for enteral eller parenteral applikasjon egnet farmasøytisk, organisk eller uor-ganisk inert bæremateriale så som vann, gelatin, gummi arabicum, melkesukker, stivelse, magnesiumstearat, talkum-, planteoljer, polyalkylenglykoler, vaseliner. De farmasøy-tiske preparatene kan foreligge i fast form, f.eks. som tabletter, drageer, suppositorier, kapsler eller i flytende form, f.eks. som løsninger, suspensjoner eller emulsjoner. Eventuelt er disse sterilisert og henholdsvis eller inneholder hjelpestoffer så som konserverings-, stabiliserings-, fukte-eller emulgeringsmidler, salter for endring av det osmotiske trykk eller puffer. De kan også inneholde andre terapeutisk verdifulle stoffer. Den orale administrering av forbindelsene ifølge oppfinnelsen er foretrukket. For voksne kommer en oral dagsdose på 0,5 - 30 mg/kg og en parenteral dagsdose på 0,0 5 10 mg/kg på tale. The compounds of formula I in D form or as racemates and their tautomers can find use as pharmaceuticals, e.g. in the form of pharmaceutical preparations, which contain them or their salts in admixture with a pharmaceutical, organic or inorganic inert carrier material suitable for enteral or parenteral application such as water, gelatin, gum arabic, milk sugar, starch, magnesium stearate, talc, vegetable oils, polyalkylene glycols, petroleum jelly. The pharmaceutical preparations can be in solid form, e.g. as tablets, dragees, suppositories, capsules or in liquid form, e.g. as solutions, suspensions or emulsions. Optionally, these are sterilized and respectively or contain auxiliaries such as preservatives, stabilisers, wetting or emulsifying agents, salts for changing the osmotic pressure or buffers. They may also contain other therapeutically valuable substances. The oral administration of the compounds according to the invention is preferred. For adults, an oral daily dose of 0.5 - 30 mg/kg and a parenteral daily dose of 0.0 5 10 mg/kg come into question.
Den aggregeringshemmende virkningen ble påvist ifølge aggre-gometermetoden til BORN [Nature 194 , 92.7 (1962)] og MICHAL und BORN [Nature 2 31,. '220 (1971)]. Den maksimale aggreger-ingshastighet ble tatt som forsøksparameter og den effek-tive konsentrasjon (EC^q) målt fra doserings-virkningskurver. The aggregation-inhibiting effect was demonstrated according to the aggregometer method of BORN [Nature 194, 92.7 (1962)] and MICHAL und BORN [Nature 2 31,. '220 (1971)]. The maximum aggregation rate was taken as an experimental parameter and the effective concentration (EC^q) measured from dosage-effect curves.
Humant blodplaterikt plasma erholdtes fra sitratbehandlet veneblod ved sentrifugering. Forsøkene ble utført med suspensjoner av' forsøkssubstansene i 0,9% NaCl eller .med løs-, ninger .av forsøkssubstansene i DMSO. Human platelet-rich plasma was obtained from citrate-treated venous blood by centrifugation. The experiments were carried out with suspensions of the test substances in 0.9% NaCl or with solutions of the test substances in DMSO.
A. Suspensjoner av forsøkssubstansene i 0,9% NaCl. A. Suspensions of the test substances in 0.9% NaCl.
0,18 ml sitratplasma ble blandet med 10 ul suspensjon av forsøksforbindelsene, inkubert 10 min. ved 37°C hvorpå aggregeringen ble utløst ved tilsetning av 10 ul av en suspensjon av kollagen-fibriller. 0.18 ml citrate plasma was mixed with 10 µl suspension of the test compounds, incubated 10 min. at 37°C whereupon the aggregation was triggered by the addition of 10 µl of a suspension of collagen fibrils.
B. Løsninger av forsøkssubstansene i DMSO. B. Solutions of the test substances in DMSO.
0,5 ml sitratplasma ble blandet med 5 ul løsning av forsøks-forbindelsen, inkubert 10 min. ved 37°C, hvorpå.■ aggregeringen ble utløst ved tilsetning av. 5 ul av en' suspensjon av kollagen-fibriller eller 5 ul av en 10 -4M adenosinfosfat-(ADP)-løsning. Som kontrollverdi tjente plasma inkubert med 0.5 ml citrate plasma was mixed with 5 ul solution of the test compound, incubated for 10 min. at 37°C, after which.■ the aggregation was triggered by the addition of. 5 µl of a suspension of collagen fibrils or 5 µl of a 10 -4 M adenosine phosphate (ADP) solution. Plasma incubated with served as a control value
DMSO. DMSO.
Blodplaterikt kaninplasma erholdtes fra arterieblod blandet med sitrat (9 mil) ved sentrif ugering. 0,6 ml plasma ble blandet med 5 p. 1 løsning av forsøkssubstansen og inkubert 10 min. ved 37°C, hvorpå aggregeringen ble utløst ved tilsetning av, 5 pl av en suspensjon av kollagen-fibriller eller . Platelet-rich rabbit plasma was obtained from arterial blood mixed with citrate (9 mil) by centrifugation. 0.6 ml of plasma was mixed with 5 p. 1 solution of the test substance and incubated for 10 min. at 37°C, after which the aggregation was triggered by the addition of, 5 µl of a suspension of collagen fibrils or .
— 4 5 ul ay en 10 M ADP-løsning. Som kontrollverdi tjente plasma inkubert med dimetylsulfoksyd. — 4 5 ul ay a 10 M ADP solution. Plasma incubated with dimethylsulfoxide served as a control value.
Resultatene er gjengitt i den nedenstående tabell. The results are reproduced in the table below.
EKSEMPEL 1 EXAMPLE 1
En løsning av 52 g brom i 200 ml iseddik tilsettes under rør-ing en suspensjon av 64 g D-l,.5-dihydro-3 , 6-dimetyl-imidazo-[2,1-b]klnazolin-2(3H)-on i 400 ml iseddik. Etter 2 timer filtreres blandingen og fellingen (97,4 g, smp. 250-255°C) vaskes med iseddik, tørkes og omkrystalliseres fra metanol og dietyleter. Man får 64,8 g D-7-brom-l,5-dihydro-3,6-dimetyl-imidazo [2,1-b]kinazolin-2(3H)-on-hydrobromid, smp. 277-279°C (spaltning) , . [a]^5 = -21,3° (c = 1%, DMSO). 25 g av dette saltet pulveriseres og suspenderes i 2 liter vann. Suspensjonen røres 5 timer og filtreres så, resten vaskes med vann og tørkes. Man får 17,2 5 g av den frie base, smp. over 300°c, [alp^"38° (i trifluoreddiksyre). A solution of 52 g of bromine in 200 ml of glacial acetic acid is added with stirring to a suspension of 64 g of D-1,5-dihydro-3,6-dimethyl-imidazo-[2,1-b]quinazolin-2(3H)-one in 400 ml glacial acetic acid. After 2 hours, the mixture is filtered and the precipitate (97.4 g, m.p. 250-255°C) is washed with glacial acetic acid, dried and recrystallized from methanol and diethyl ether. 64.8 g of D-7-bromo-1,5-dihydro-3,6-dimethyl-imidazo [2,1-b]quinazolin-2(3H)-one hydrobromide are obtained, m.p. 277-279°C (decomposition) , . [α]^5 = -21.3° (c = 1%, DMSO). 25 g of this salt is powdered and suspended in 2 liters of water. The suspension is stirred for 5 hours and then filtered, the residue is washed with water and dried. You get 17.25 g of the free base, m.p. above 300°c, [alp^"38° (in trifluoroacetic acid).
Utgangsmaterialet kan fremstilles som følger: The starting material can be prepared as follows:
En løsning av 302 g 3-nitro-o-xylen i 200 ml karbontetra-klorid tilføres under røring en suspensjon av 391. g N-brom-succin.i.mid og 10 g dibenzoylperoksyd i 1000 ml karbontetra-klorid. Blandingen oppvarmes.3 til 4 timer ved tilbakeløps-temperatur, og kjøles så til romtemperatur og filtreres. Filtratet inndampes til tørrhet. Man får 4 80 g av en blanding av isomerer, 2-metyl-6-nitrobenzylbromid og 2-metyl-3-nitrobenzylbromid. ■ A solution of 302 g of 3-nitro-o-xylene in 200 ml of carbon tetrachloride is added with stirring to a suspension of 391 g of N-bromosuccinimide and 10 g of dibenzoyl peroxide in 1000 ml of carbon tetrachloride. The mixture is heated for 3 to 4 hours at reflux temperature, and then cooled to room temperature and filtered. The filtrate is evaporated to dryness. You get 480 g of a mixture of isomers, 2-methyl-6-nitrobenzyl bromide and 2-methyl-3-nitrobenzyl bromide. ■
En løsning av 900 ml trietylamin ill etanol tildryppes en løsning av 380 g D-alaninetylester-hydroklorid i 1,5 1 etanol. Reaksjonsblandingen som er oppvarmet til 70° blandes med en løsning av den ovenfor nevnte' 4 80 g isomerblanding ill etanol. Blandingen behandles 3 til 4 timer ved til-bakeløpstemperatur og inndampes til tørrhet. Produktet blandes med 1/5 1 vann og ekstraheres med vann og metylen-klorid. Ekstraktene vaskes med vann, tørkes og inndampes. Man får 534 g av en blanding av isomerene N-(2-metyl-6-nitrobenzyl)- og N-(2-metyl-3-nitrobenzyl)-D-alanin-etyl-ester. A solution of 900 ml of triethylamine in ethanol is added dropwise to a solution of 380 g of D-alanine ethyl ester hydrochloride in 1.5 1 of ethanol. The reaction mixture, which has been heated to 70°, is mixed with a solution of the above-mentioned 4 80 g isomer mixture in ethanol. The mixture is treated for 3 to 4 hours at reflux temperature and evaporated to dryness. The product is mixed with 1/5 1 water and extracted with water and methylene chloride. The extracts are washed with water, dried and evaporated. 534 g of a mixture of the isomers N-(2-methyl-6-nitrobenzyl)- and N-(2-methyl-3-nitrobenzyl)-D-alanine ethyl ester are obtained.
En løsning av denne blandingen ill etanol hydrogeneres over 50 g av en Pd/C-katalysator. Etter fullstendig hydro-genering frafiltreres katalysatoren. Filtratet som inneholder N-(2-amino-6-metylbenzyl)- og N-(2-amino-3-metylben-zyl)-D-alaninetylester, tilsettes 186 g brqmcyan. Blandingen røres 48 timer, gjøres så alkalis.k ved tilsetning av 300 ml konsentrert ammoniakk og røres 1-2 timer. Felling-, en' filtreres,, vaskes med vann og tørkes. Man får 54,4 g D-1,5-dihydro-3,6-dimetyl-imidazo[2,1-b]kiriazolin-2(3H)-on. A solution of this mixture in ethanol is hydrogenated over 50 g of a Pd/C catalyst. After complete hydrogenation, the catalyst is filtered off. To the filtrate containing N-(2-amino-6-methylbenzyl)- and N-(2-amino-3-methylbenzyl)-D-alanine ethyl ester, 186 g of brqmcyan are added. The mixture is stirred for 48 hours, then made alkaline by adding 300 ml of concentrated ammonia and stirred for 1-2 hours. The precipitate is filtered, washed with water and dried. 54.4 g of D-1,5-dihydro-3,6-dimethyl-imidazo[2,1-b]kiriazolin-2(3H)-one are obtained.
EKSEMPEL 2 EXAMPLE 2
På analog måte med eksempel 1 fremstilles følgende forbindelser: D,L-7-brom-l,5-dihydro-3,6-dimetyl-imidazo[2,1-b]kinazolin-2(3H)-on, smp. 305°C (spaltning), smp. av hydrobromidet 272-276°C, smp. av hydrokloridet: over 300°C? D-7-brom-6-klor-l,5-dihydro-3-metyl-imidazo[2,1-b]kinazolin-2(3H)-on, smp. 310-312°C, smp. av hydrokloridet 290°C (spaltning) . In an analogous manner to example 1, the following compounds are prepared: D,L-7-bromo-1,5-dihydro-3,6-dimethyl-imidazo[2,1-b]quinazolin-2(3H)-one, m.p. 305°C (decomposition), m.p. of the hydrobromide 272-276°C, m.p. of the hydrochloride: above 300°C? D-7-bromo-6-chloro-1,5-dihydro-3-methyl-imidazo[2,1-b]quinazolin-2(3H)-one, m.p. 310-312°C, m.p. of the hydrochloride 290°C (decomposition) .
EKSEMPEL 3 EXAMPLE 3
N- (2-amino-6-klor-5-metoksy-benzyl)-D-alaninetylester, frem-stilt ut fra 2-klor-3-metoksy-6-nitrotoluen og 2-klor-3-metoksy-6-nitrobenzylbromid og N-(6-klor-5-metoksy-2-nitroben-zyl)-D-alaninetylester, overføres ved den i eksempel 1 be-skrevne overføring av N-(2-amino-6-metylbenzyl)-D-alaninetyl-. ester i D-l,5-dihydro-3,6-dimetyl-imidazo[2,1-b]kinazolin-2(3H)-on i D-6-klor-l, 5-dihydro-7-metoksy-3-metyl-.imidazo-[2,1-b]kinazolin-2(3H)-on, smp. av hydrokloridet 280°C. N-(2-amino-6-chloro-5-methoxy-benzyl)-D-alanine ethyl ester, prepared from 2-chloro-3-methoxy-6-nitrotoluene and 2-chloro-3-methoxy-6-nitrobenzyl bromide and N-(6-chloro-5-methoxy-2-nitrobenzyl)-D-alanine ethyl ester, is transferred by the transfer described in example 1 of N-(2-amino-6-methylbenzyl)-D-alanine ethyl- . ester in D-1,5-dihydro-3,6-dimethyl-imidazo[2,1-b]quinazolin-2(3H)-one in D-6-chloro-1,5-dihydro-7-methoxy-3-methyl -.imidazo-[2,1-b]quinazolin-2(3H)-one, m.p. of the hydrochloride 280°C.
EKSEMPEL 4 EXAMPLE 4
På vanlig måte fremstilles tabletter med følgende sammensetning: In the usual way, tablets are prepared with the following composition:
EKSEMPEL 5 EXAMPLE 5
På vanlig måte fremstilles gelatin-stikkapsler med følgende sammensetning: In the usual way, gelatin suppositories are produced with the following composition:
EKSEMPEL 6 EXAMPLE 6
På vanlig måte fremstilles en injeksjonsløsning med følgende sammensetning: In the usual way, an injection solution is prepared with the following composition:
Claims (4)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/050,395 US4256748A (en) | 1977-07-25 | 1979-06-20 | Imidazo[2,1-b]quinazolin-2(3H)-ones and pharmaceutical compositions for treatment and prophylaxis of cardiac insufficiency and cardiac failure |
| CH360080 | 1980-05-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO801843L true NO801843L (en) | 1980-12-22 |
Family
ID=25693404
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO801843A NO801843L (en) | 1979-06-20 | 1980-06-19 | NEW CHINAZOLINE DERIVATIVES AND PHARMACEUTICAL PREPARATIONS |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0021338B1 (en) |
| AU (1) | AU538119B2 (en) |
| CA (1) | CA1131631A (en) |
| DE (1) | DE3065273D1 (en) |
| DK (1) | DK259380A (en) |
| ES (3) | ES8105321A1 (en) |
| FI (1) | FI66870C (en) |
| IL (1) | IL60325A (en) |
| MC (1) | MC1332A1 (en) |
| NO (1) | NO801843L (en) |
| NZ (1) | NZ194046A (en) |
| PH (1) | PH16369A (en) |
| PT (1) | PT71411B (en) |
| YU (1) | YU161580A (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0054180A3 (en) * | 1980-12-16 | 1982-12-01 | F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft | Process for the preparation of imidazoquinazoline derivatives |
| US4783467A (en) * | 1985-06-05 | 1988-11-08 | Pfizer Inc. | Tetrahydroimidazoquinazolinone inotropic agents |
| US6388073B1 (en) * | 2000-07-26 | 2002-05-14 | Shire Us Inc. | Method for the manufacture of anagrelide |
| US7700608B2 (en) | 2004-08-04 | 2010-04-20 | Shire Holdings Ag | Quinazoline derivatives and their use in the treatment of thrombocythemia |
| US8426429B2 (en) | 2004-08-06 | 2013-04-23 | Jansssen Pharmaceutica N.V. | 2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE) |
| US8436006B2 (en) | 2004-08-06 | 2013-05-07 | Jansssen Pharmaceutica N.V. | 2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE) |
| US8383637B2 (en) | 2004-08-06 | 2013-02-26 | Jansssen Pharmaceutica N.V. | 2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE) |
| US7910597B2 (en) | 2006-11-28 | 2011-03-22 | Shire Llc | Substituted quinazolines |
| US8304420B2 (en) | 2006-11-28 | 2012-11-06 | Shire Llc | Substituted quinazolines for reducing platelet count |
| GB0623750D0 (en) | 2006-11-28 | 2007-01-10 | Shire Llc | Substituted quinazolines |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3932407A (en) * | 1973-11-19 | 1976-01-13 | Bristol-Myers Company | Optionally substituted 1,2,3,5-tetrahydroimidezo(2,1-b)-quinazolin-2-ones and 6(H)-1,2,3,4-tetrahydropyimido(2,1-b)quinazolin-2-ones |
| BE794964A (en) * | 1972-02-04 | 1973-08-02 | Bristol Myers Co | NEW HYPOTENSING AGENTS AND METHOD FOR PREPARING THEM |
| US3988340A (en) * | 1975-01-23 | 1976-10-26 | Bristol-Myers Company | 6-Alkoxymethyl-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-ones and 7-alkoxymethyl-6-[H]-1,2,3,4-tetrahydropyrimido[2,1-b]quinazolin-2-ones |
| NL7807507A (en) * | 1977-07-25 | 1979-01-29 | Hoffmann La Roche | TRICYCLICAL CONNECTIONS. |
| US4146718A (en) * | 1978-04-10 | 1979-03-27 | Bristol-Myers Company | Alkyl 5,6-dichloro-3,4-dihydro-2(1h)-iminoquinazoline-3-acetate hydrohalides |
-
1980
- 1980-06-06 CA CA353,659A patent/CA1131631A/en not_active Expired
- 1980-06-13 NZ NZ194046A patent/NZ194046A/en unknown
- 1980-06-13 FI FI801910A patent/FI66870C/en not_active IP Right Cessation
- 1980-06-16 IL IL60325A patent/IL60325A/en unknown
- 1980-06-17 AU AU59339/80A patent/AU538119B2/en not_active Ceased
- 1980-06-17 DK DK259380A patent/DK259380A/en not_active Application Discontinuation
- 1980-06-18 DE DE8080103396T patent/DE3065273D1/en not_active Expired
- 1980-06-18 PT PT71411A patent/PT71411B/en unknown
- 1980-06-18 EP EP80103396A patent/EP0021338B1/en not_active Expired
- 1980-06-18 MC MC801454A patent/MC1332A1/en unknown
- 1980-06-19 YU YU01615/80A patent/YU161580A/en unknown
- 1980-06-19 ES ES492573A patent/ES8105321A1/en not_active Expired
- 1980-06-19 NO NO801843A patent/NO801843L/en unknown
- 1980-06-20 PH PH24171A patent/PH16369A/en unknown
-
1981
- 1981-02-16 ES ES499455A patent/ES8206524A1/en not_active Expired
- 1981-02-16 ES ES499454A patent/ES499454A0/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| IL60325A (en) | 1983-06-15 |
| DK259380A (en) | 1980-12-21 |
| AU5933980A (en) | 1981-01-08 |
| ES499455A0 (en) | 1982-08-16 |
| YU161580A (en) | 1983-04-30 |
| AU538119B2 (en) | 1984-08-02 |
| FI66870C (en) | 1984-12-10 |
| FI801910A7 (en) | 1980-12-21 |
| FI66870B (en) | 1984-08-31 |
| IL60325A0 (en) | 1980-09-16 |
| PT71411B (en) | 1981-12-11 |
| MC1332A1 (en) | 1981-04-21 |
| EP0021338A1 (en) | 1981-01-07 |
| ES8206524A1 (en) | 1982-08-16 |
| ES8201164A1 (en) | 1981-12-01 |
| CA1131631A (en) | 1982-09-14 |
| EP0021338B1 (en) | 1983-10-12 |
| NZ194046A (en) | 1982-05-25 |
| ES492573A0 (en) | 1981-06-01 |
| ES499454A0 (en) | 1981-12-01 |
| PT71411A (en) | 1980-07-01 |
| DE3065273D1 (en) | 1983-11-17 |
| PH16369A (en) | 1983-09-14 |
| ES8105321A1 (en) | 1981-06-01 |
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