NO133669B - - Google Patents

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NO133669B
NO133669B NO4295/70A NO429570A NO133669B NO 133669 B NO133669 B NO 133669B NO 4295/70 A NO4295/70 A NO 4295/70A NO 429570 A NO429570 A NO 429570A NO 133669 B NO133669 B NO 133669B
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pyridone
methyl
mixture
preparation
compounds
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NO4295/70A
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NO133669C (no
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B E Witzel
T-Y Shen
P M Graham
R L Clark
A A Pessolano
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Merck & Co Inc
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    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/84—Nitriles
    • C07D213/85—Nitriles in position 3
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    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Description

Foreliggende oppfinnelse angår en analogifremgangsmåte ved fremstilling av en ny gruppe terapeutisk aktive substituerte aminopyridoner, som er nyttige ved behandling av inflammasjon og som også oppviser sterk analgetisk og antipyretisk aktivitet.
De nye pyridoner som fremstilles ifølge oppfinnelsen, har strukturformelen:
hvor R <1> er lavere alkyl, R <2>er hydrogen eller lavere alkanoyl, og 3
R er lavere alkanoyl.
Forbindels ene med formel I fremstilles ifølge oppfinnelsen
ved at en forbindelse av den generelle formel:
hvor R<1> er som ovenfor angitt, reduseres under samtidig eller på-følgende acylering.
Fra Chemical Abstraets J50, 2576, er det kjent å frem-
stille 3(5)-amino-, 5-acetamido- og 5-benzamido-l-methyl-2(lH)-pyridon, men intet er angitt om slike forbindelsers aktivitet.
I motsetning til foreliggende fremgangsmåteforbindelser har disse kjente forbindelser en methylgruppe i 1-stilling.
Fra DOS 1.810.822 er det kjent å fremstille pyridoner som
er substituert med en carbocyclisk eller heterocyclisk aryl-
gruppe og eventuelt andre substituenter, og som angis å ha anti-inf lammas jonsvirkning og være fri for bivirkninger. Foreligg-
ende fremgangsmåteforbindelser har ingen slik arylsubstituent på pyridonringen, og har, foruten antiinflammatorisk, også analgetisk og antipyretisk aktivitet.
De substituerte pyridoner som fremstilles ifølge oppfinnelsen, har en høy grad av antiinflammatorisk, analgetisk og antipyretisk aktivitet. De er verdifulle ved behandlingen av arthritiske og dermatologiske lidelser eller lignende tilstander som er responsive til antiinflammatoriske droger. Generelt kan de anvendes for en lang rekke tilstander-hvor én eller flere av symp-tomene på inflammasjon, feber og smerte viser seg. Innbefattet i denne kategori er lidelser som rheumatoid arthritis, osteo arthritis, gikt, smittsom arthritis og rheumatisk feber. Som nevnt ovenfbr, har fremgangsmåteforbindelsene også en nyttig grad av analgetisk og antipyretisk aktivitet.
For disse formål kan fremgangsmåteforbindelsene administreres oralt, lokalt, parenteralt, ved inhaleringsspray eller rektalt i formuleringer inneholdende konvensjonelle ikke-giftige farmasøytisk godtagbare bærere, hjelpestoffer og væsker. Uttrykket parenteralt er her anvendt for å innbefatte subcutane injeksjoner, intravenøs, intramuskulær, intrasternal injeksjon eller infusjonsmetoder„ Foruten til behandling av varmblodige dyr som mus, rotter, hester, hunder, katter, etc;, er fremgangsmåteforbindelsene virksomme ved. behandling av mennesker.
De farmasøytiske preparater inneholdende den aktive bestanddel kan være i en form egnet for oral anvendelse, f.eks. som tab-letter., pastiller, vandige eller oljesuspensjoner, dispergerbare pulvere eller korn, emulsjoner, hårde eller myke kapsler eller siruper eller eliksirer. Preparater beregnet på oral anvendelse kan fremstilles på i og for seg kjent vis. Tabletter.kan være ubelagte eller de kan være belagt ved kjente metoder for å sinke oppbryt-ningen og absorbsjonen i fordøyelseskanalen og derved frembringe en protrahert virkning over en lengre periode.
Preparater for oral anvendelse kan også være i form av hårde gelatinkapsler hvori den aktive bestanddel er blandet med et inert fast fortynningsmiddel, eller som myke gelatinkapsler hvor den aktive bestanddel er blandet med vann eller et oljemedium.
Vandige suspensjoner inneholder de aktive forbindelser i blanding med hjelpestoffer egnet for fremstilling av vandige suspensjoner.
Oljesuspensjoner kan være formulert ved å suspendere den aktive forbindelse i en vegetabilsk olje.
Dispergerbare pulvere og korn egnet for fremstilling av en vandig suspensjon ved tilsetning av vann har den aktive bestanddel i blanding med et dispergerings- eller fuktemiddel, suspensjons-middel og ett eller flere konserveringsmidler.
De farmasøytiske preparater med fremgangsmåteforbindelsene kan også være i form av olje-i-vannemulsjoner.
Siruper og eliksirer kan være formulert med søtemidler. De farmasøytiske preparater kan også være i form av et sterilt injiser-bart preparat f.eks. som en steril injiserbar vandig eller oljesus-pensjon. Det sterile injiserbare preparat kan også være en steril injiserbar oppløsning eller suspensjon i et ikke-giftig parenteralt godtagbart fortynningsmiddel eller oppløsningsmiddel f.eks. som en oppløsning i 1,3-butandiol. Blant de godtagbare medier og oppløs - ningsmidler som kan anvendes, er vann, Ringer's oppløsning og iso-tonisk natriumkloridoppløsning. Dessuten anvendes sterile, ikke-flyktige oljer konvensjonelt som oppløsnings- eller suspensjons - medium.
For lokal anvendelse anvendes kremer, salver, geléer, oppløs-ninger eller suspensjoner, etc., inneholdende de antiinflammatoriske midler.
Doser av størrelsesorden 20 mg til 7 g pr. dag er nyttige ved behandling av de ovennevnte lidelser. Eksempelvis behandles inflammasjon effektivt og antipyretisk og .analgetisk aktivitet gir seg tilkjenne ved administrasjon av fra 0,3 - lOO mg fremgangs-måtef o-rbindelse pr . kg legemsvekt pr. dag. Fra 2 mg til 5 mg j>r. kg legemsvekt og særlig fra 4 mg til 20 mg/kg pr. dag gir meget effektive resultater.
Mengden av aktiv bestanddel som kan kombineres med bærér-materialene for å danne en enkelt doseform, vil variere avhengig av den vert som behandles, og administrasjonsmåten. Eksempelvis kan et preparat beregnet på oral administrasjon til mennesker inneholde fra 5 mg til 5 Q aktiv bestanddel opparbeidet med en passende og bekvem mengde bærermateriale som kan variere fra 5 til 95% av totalpreparatet. Enhetsdoseformer vil i alminnelighet inneholde mellom 25 mg og 500 mg aktiv bestanddel.
Den spesifikke dosemengde for en spesiell pasient vil imidler-tid avhenge av en rekke faktorer innbefattende aktiviteten av den spesielle forbindelse som anvendes, alderen, legemsvekten, den alminnelige helsetilstand, kjønn, diett, administrasjonstid, admin-istras jonsvei, utskillelseshastighet, drogekombinasjon og graden av den spesielle lidelse som behandles.
En bekvem måte for å fremstille fremgangsmåteforbindelsene, som illustrert i det følgende prosesskjema, innbefatter generelt oxydasjon av et pyridin (A) til det tilsvarende N-oxyd (F). N-oxydef kan overføres til 2-[lH]-pyridonet ved oppvarmning med laverealkansyreanhydrid, hvilket fører til dannelsen av 2-acyloxy-pyridinet, som ved sur, nøytral eller basisk hydrolyse gir 2-[lH]-pyridon (E). Nitrering av pyridonet (E) vil resultere i det til-svarende nitropyridon (II). Nitropyridonet (II) kan fremstilles på en alternativ måte ved aminering av pyridinet (A) for å danne aminopyridinet (B) . Aminopyridinet (B) kan enten nitreres for å danne et amino-nitropyridin (C) som så diazoteres til nitropyridonet (II) eller alternativt overføres aminopyridinet til pyridonet (E) og nitreres så for å danne nitropyridinet (II), som er utgangsmateri-alet ved foreliggende fremgangsmåte. Reduksjon av nitropyridonet (II) vil føre til dannelsen av aminopyridonet (H) ifølge oppfinnelsen, idet dette aminopyridon (H) ved samtidig acylering ifølge oppfinnelsen overføres til de substituerte aminopyridoner (I).
r-*- t og R er som ovenfor angitt.
Eksempel
Fremstilling av utqanqsmaterialer
A. Fremstilling av 2- amino- 4- methylpyridin
Til en omrørt suspensjon av friskt fremstilt natriumamid (fra 24 g natrium) i 90 ml dimethylanilin (fremstilt ved fremgangs-måten i Organic Reactions, Vol. I) tilsettes 0,8 mol 4-methylpyridin, og den dannede blanding oppvarmes langsomt til ca. 155°C. Efter at hydrogenutviklingen er avtatt betraktelig, får reaksjonen lov til å fortsette i 5 timer og derpå avkjøles. Blandingen spaltes med l6o ml 5%-ig natriumhydroxydoppløsriing og ekstraheres med benzen. Benzenekstraktene tørres, inndampes i vakuum og det oljeaktige residuum krystalliseres fraksjonert fra ether-petrol-ether., hvilket gir 2-amino-4-methylpyridin.
B. Fremstillingen av 2- amino- 4- methyl- 3- nitropyridi-
Til en isavkjølt, omrørt blanding av 0,19 mol 2-amino-4-methylpyridinet fra trinn A i 120 ml konsentrert svovelsyre tilsettes 15»2 ml konsentrert salpetersyre i 30 ml svovelsyre i løpet av 1,3 timer, idet temperaturen av blandingen holdes under 6°C. Efter oppvarmning til værelsetemperatur oppvarmes blandingen langsomt til 92°C, holdes i 3 timer ved denne temperatur, avkjøles og tilsettes så til 2 liter is. Blandingen gjøres så basisk med konsentrert ammoniumhydroxyd. Den erholdte blanding ekstraheres med kloroform, kloroformen fjernes i vakuum og residuet damp-' destilleres. Destillatet oppsamles inntil destillasjonskolben er fri for de mere flyktige isomerer. Ekstraksjon av destillatet med methylenklorid gir 2-amino-4-methyl-3-nitxopyridin.
C. Fremstilling av 4-methyl-3-nitro-2-[lH]-pyridon
Til en omrørt oppløsning av 0,032 mol 2-amino-4-methy1-3-nitropyridin fra trinn B i en blanding av 9 ml svovelsyre og 90 ml vann ved 5° C tilsettes en konsentrert vandig oppløsning av 2,4 g (0,022 mol) natriumnitrit mens temperaturen holdes under 10°C ved utvendig kjøling. Blandingen får lov til å oppvarmes til værelsetemperatur, oppvarmes til 45°C, avkjøles, filtreres, og det opp-samlede produkt vaskes med "vann og tørres, hvorved man får 4-methyl-3-nitro-2-[lH]-pyridon. Omkrystallisasjon gir det rene materiale.
Fremstilling av sluttprodukt
D. Fremstilling av 3-acetamido-4-methyl-2-[lH]-pyridon og N-(4~
methyl- 2-[ lH]- pyridon- 3- yl)- acetimid
En blanding av 3,0 g (0,02 mol) 4-methyl-3-nitro-2-[lH]-pyridon, 100 ml eddiksyreanhy.drid, 0,5 ml eddiksyre og 1,0 g 5%-ig palladium-på-carbon omsettes i en hydrogenatmosfære (2,8 kg/cm 2) ved værelsetemperatur. Da den teoretiske mengde hydrogen var opp-tatt, ble blandingen filtrert og konsentrert i vakuum til ca. 10 g. Oljen ble så tilsatt til 50 ml isvann, omrørt over natten og den vandige blanding inndampet i vakuum til en tykk olje som størknet ved triturering med ether under dannelse av et hvitt, fast stoff. Fraksjonert omkrystallisasjon fra aceton ga acetatet, 3-acetamido-4-methyl-2-[lH]-pyridon med smeltepunkt 218-220,5°C, og imidet, N-(4-methyl-2-[lH]-pyridon-3-yl)-acetimid, smeltepunkt 159-163°C.

Claims (1)

  1. Analogifremgangsmåte ved fremstilling av terapeutisk aktive forbindelser av den generelle formel:
    1 2 hvor R er lavere alkyl, R er hydrogen eller lavere alkanoyl,. og Ru 3 er lavere alkanoyl, karakterisert ved at en forbindelse av den generelle formel: hvor R er som ovenfor angitt, reduseres under samtidig eller på-følgende acylering.
NO4295/70A 1969-11-12 1970-11-11 NO133669C (no)

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US87605969A 1969-11-12 1969-11-12

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NO133669B true NO133669B (no) 1976-03-01
NO133669C NO133669C (no) 1976-06-09

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NO4295/70A NO133669C (no) 1969-11-12 1970-11-11

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US (1) US3654291A (no)
JP (1) JPS4815950B1 (no)
BE (1) BE758759A (no)
CA (1) CA968803A (no)
CH (1) CH549569A (no)
DE (1) DE2055513A1 (no)
ES (1) ES385397A1 (no)
FR (1) FR2073341B1 (no)
GB (1) GB1299100A (no)
IL (1) IL35568A (no)
NL (1) NL7015826A (no)
NO (1) NO133669C (no)
SE (1) SE386439B (no)
ZA (1) ZA707636B (no)

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US3721676A (en) * 1969-11-12 1973-03-20 Merck & Co Inc Certain 3-amino-2(1h)pyridones
GB1419994A (en) * 1973-05-03 1976-01-07 Smith Kline French Lab Heterocyclicalkylaminotheterocyclic compounds methods for their preparation and compositions comprising them
US4035374A (en) * 1973-05-03 1977-07-12 Smith Kline & French Laboratories Limited Imidazolyl alkylaminopyridone and pyridinethione compounds
US4578459A (en) * 1973-05-03 1986-03-25 Smithkline & French Laboratories Limited Heterocyclic alkylaminoheterocycles
US4467087A (en) * 1973-05-03 1984-08-21 Smith Kline & French Laboratories Limited 1,2,4-Triazines
US4260744A (en) * 1973-05-03 1981-04-07 Smith Kline & French Laboratories Limited Pharmacologically active compounds
DE3106460A1 (de) * 1980-03-03 1982-01-28 Sandoz-Patent-GmbH, 7850 Lörrach 2(1h)-pyridinon-derivate, ihre herstellung und sie enthaltende pharmazeutische zubereitungen
US4371537A (en) * 1981-08-13 1983-02-01 The Dow Chemical Company Sulfur-substituted phenoxypyridines having antiviral activity
US4524149A (en) * 1982-03-15 1985-06-18 Sterling Drug Inc. 5-Alkanoyl-6-alkyl-2(1H)-pyridinones, their preparation and their cardiotonic use
US4412077A (en) * 1982-03-15 1983-10-25 Sterling Drug Inc. Process for preparing 5-(lower-alkanoyl)-6-(lower-alkyl)-2(1H)-pyridinone
US4451469A (en) * 1982-12-16 1984-05-29 Sterling Drug Inc. Selected 6-alkyl-and 4,6-dialkyl-2(1H)-pyridinones as cardiotonics
US4681873A (en) * 1985-07-29 1987-07-21 Warner-Lambert Company 4-amino-3-halo-2-pyridinone nucleoside and nucleotide compounds
US5032602A (en) * 1988-12-14 1991-07-16 Bayer Aktiengesellschaft Inhibiting HMG-CoA reductase with novel substituted 2-pyridones and pyrid-2-thiones
US5164506A (en) * 1988-12-14 1992-11-17 Bayer Aktiengesellschaft Substituted 2-pyridones and pyrid-2-thiones compounds
US5308854A (en) * 1990-06-18 1994-05-03 Merck & Co., Inc. Inhibitors of HIV reverse transcriptase
GB9016578D0 (en) * 1990-07-27 1990-09-12 Ici Plc Fungicides
KR100901931B1 (ko) 2002-02-14 2009-06-10 파마시아 코포레이션 Ｐ３８ ｍａｐ 키나제의 조절제로서의 치환된 피리디논
JP4164031B2 (ja) * 2002-02-14 2008-10-08 ファルマシア コーポレーション Ｐ３８ｍａｐキナーゼのモジュレータとしての置換されたピリジノン
AU2007202607B2 (en) * 2002-02-14 2008-12-18 Pharmacia Corporation Substituted Pyridinones as Modulators of p38 MAP Kinase
CL2004002050A1 (es) * 2003-08-13 2005-06-03 Pharmacia Corp Sa Organizada B Compuestos derivados de piridinonas sustituidas; su uso en el tratamiento de afecciones causadas o exacerbadas por actividad p38 map kinasa y/o tnf no regulada, tales como inflamaciones, tumores, sida y otros.
CN109311813B (zh) * 2016-04-18 2023-02-28 斯克利普斯研究院 钯催化的间位-c-h官能化的通用型配体
CN116120225B (zh) * 2023-01-06 2024-09-06 利尔化学股份有限公司 一种除去三氯吡氧乙酸乙酯中吡啶酮杂质的方法及其应用

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DE596728C (de) * 1932-10-26 1934-05-09 Chem Fab Von Heyden Akt Ges Verfahren zur Darstellung von 2-Oxy-5-aminopyridin bzw. dessen Kernsubstitutionsprodukten
DE626687C (de) * 1934-07-05 1936-09-01 Chem Fab Von Heyden Akt Ges Verfahren zur Darstellung von Alkoxyaminopyridinen
NL6816241A (no) * 1967-12-01 1969-06-03

Also Published As

Publication number Publication date
NL7015826A (no) 1971-05-14
IL35568A (en) 1974-09-10
IL35568A0 (en) 1971-01-28
GB1299100A (en) 1972-12-06
DE2055513A1 (de) 1971-05-19
CH549569A (de) 1974-05-31
BE758759A (fr) 1971-05-10
ZA707636B (en) 1972-06-28
NO133669C (no) 1976-06-09
ES385397A1 (es) 1973-11-01
FR2073341A1 (no) 1971-10-01
SE386439B (sv) 1976-08-09
FR2073341B1 (no) 1973-08-10
US3654291A (en) 1972-04-04
JPS4815950B1 (no) 1973-05-18
CA968803A (en) 1975-06-03

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