HUE028799T2 - Azol-származék - Google Patents

Azol-származék Download PDF

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HUE028799T2
HUE028799T2 HUE12843663A HUE12843663A HUE028799T2 HU E028799 T2 HUE028799 T2 HU E028799T2 HU E12843663 A HUE12843663 A HU E12843663A HU E12843663 A HUE12843663 A HU E12843663A HU E028799 T2 HUE028799 T2 HU E028799T2
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Hungary
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compound
formula
chem
propan
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HUE12843663A
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English (en)
Inventor
Mitsukane Yoshinaga
Takeshi Kuwada
Naoki Miyakoshi
Tomoko Ishizaka
Daisuke Wakasugi
Shin-Ichi Shirokawa
Nobutaka Hattori
Youichi Shimazaki
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Taisho Pharmaceutical Co Ltd
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Publication of HUE028799T2 publication Critical patent/HUE028799T2/hu

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08—Bridged systems
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/537—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
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Claims (9)

  1. , Szabadalmi igénypontok h Ci) képiéit! ezokszámmzék l!. képi) Cil
    [az 0} képletben 1; jekttlése hidrogénatom, €<..5 alkilcsopoté (a CPs »Mhmpùst adott esetben ssubsÂtâîva van sgy-•àârotn csoportiéi, amelyek hklroxtlcsoporí, hakt-génakonok.. eistto··, C3..7 cikbstkil-· és €;.·> alkoxicsoport közöl vannak ksváistsztva), Cv; elklosikdesopart vasa·· P-S-mgó -elüsö hete melk lus; ^jelentése hidrogénatom vagy €.^ slküsssoport; R1 jelentése aril- vagy feeterosrffcsopott lat srth és a hemroariksopsxt adok esetben xzubsztlMIva vart egy vagy két csoporttal, amelyek Cm alkcxt-, Cm alkilcsoport, halogétmomok, trifluorotetiK rrtfluorsneioxh elano-. hiároxil-, diütmrmetoxt és Cm alktlszulfbmicsopoit közöl vannak kiválómmá >; R* és K;' azonos vagy különböző lehet, és jelentése hidrogénatom, €;.< ítsklksoporl ta Cm aik besöpöri adott esetben szt-bszilPtálvs van agy-három csoporttal, amelyek hklroxtlcsoporí, halogéoatootok, eiamv, G;.-cikktalkb-- és C(,< alkoxlcsoport közül vannak kiválasztva), CVr eildoaikl lesöpöri vagy egy 4~S-tagti teiltet; v&amp;gy telítetten hetet ooikkts, amely gyűrűjében egy vagy több nitrogén', oxigén-- vagy kénatomot tartalmaz í&amp; 4-S-t&amp;gö lelned vagy telítetlen heterocikSus adott esetben szubsatitnálva van egy vagy két csoporttal, amelyek hldroxiK €;,·> éhül', Cm alkosicsoporU haSogénatomok, dann-, Cs..; alkanod- és trifhmrmmltajport közül vannak kiválasztva), vagyis1 és iC a szomszédos nitrogénatotntnal egyik- 4-8-íagú telített vagy telítetlen heteroetklust képeznek, amely gyűrűjében adót- esetben egy vagy-' több nitrogén--. oxigén- vagy kéitatomol rastakmtz a szomszédos ntirogénaíontott túlmenően (a ά-R-tagà telített vagy telítetlen hetetoctklus adott esetlen szobsztttuátva van egy vagy két csoporttal amelyek hidtoxül-, CG altdlcsopori (s C5,s slkllesoport adott esetben szubsxtihiáiva van egy vagy·· két hköoxücsoporttáí}, Cm alkoslcsoport, halögénatotnök, cta-to-. C;·,, alkattól!-, 0x0-, amhxikarbomi-, tnotto-C m alldlíxalnokarbonü-, di-CG tdkbstmaekarbcGK tník-oetoelil·-, aenino-, mono-Cns alktlatnitto», dt--Cj„5 aMlasniao·' da Cm slktmoilam'-noOsttpott körül varrnak kiválasztva, és a 4- Gagé telített vagy teiltet lea IxRerodldas adott, esetbe» tartalmaz egy C,^ edkiléncsoportm, amely a gyűrűben két különbőzé szénatomot összeköt}.. vagy 2-oxa-6»amptr(í{3.3jhept-6-il- vagy 7--oxa--x-axtasp;ro(3.5jnori--2-H'CSOpottöt képezo«k; stx adott esetben szubsztltoált azol-györtk amely az alábbi (a) képlett®! van lakva, p. képlj
    (α) as aiâbhi (ïî) képkxvesoponban bemutatott szerkezetsk bársseivikével rentkikezik, p, képi.]
    Ry jelentése hidrogénatom vagy C).5 aildlesoport; X ' ds X“ jelentés® úgy van meghatározva, hogy i) araikor X! jelentése egyeskbtés vagy -CO- képkttil bsopoxt, akkor X? jstekése *£),$ aíkiléu- vágj1 -Dj'Ck-s alMé-nc-soportt és il) amikor X''jelentése CONE>:i--kdpseiü csoport, akkor Xs jeisuksc egyeskötés; H*1 jelentése hidrogénatom vagy Ci.?, slkiicsoport; és as A gyérü jelentése benzol-gyűrű, b4sgá aromás herermäkKsu (a beasobgyüní és s b-îagè aromás isereroeikiiss ad ob esőiben szuhsætittjâlv« van egy vágj- kér csoporttal, amelyek halogénat-mtok és Cs.$ alkoscícsoport kdeik vasinak kiválasztva), 4-8-tagé teiltet; vagy részben telked«· behetoeikkis, amely egy vágy két altrogén&amp;tomot taslalmaa: (sí 4-84sgü telített vagy tektsüen heietoclkhis adott .esetben szuhszHtnálva van egy oxoesopntttaS) vagy C5.-j elkloaSkatt}, vágyás aatokssármasók gyógys»«rómstiteg elfogadható sója.
  2. 2. Az j. igénypont seerinu azol-származték vagy' ennek gyégyszerésssríieg «itogatiható sósa, shot a fenti (.1) képletben &amp;' és R" azonos vargy különböző Met» és jelentése Mâmgésmm* C%j alkiksopozt (a €*.s a&amp;ilcsnpoiit adott eseten szabszSltnälvn w sgy-'nárom esoysarttsl, amelyek biátwilesőport, hteg&amp;tatomok, olano-,. €** dkloaikil- és €;.<. alkoxiesopoti késül vmrnak kiválásává;, Ok.? etktoalkilcsopost vagy 4-Rfegű telkeit vagy tetette heteroeikkts, amely gyűrűjében egy vagy több nittog&amp;K oxigén' vagy kína-omol tartateaz fa 4-8-tagd íeakií vagy telítetlen beteroeiklas adott esetben szubssbtnaiva van egy vagy két csoporttá], amelyek hidrexil-, C},$ alkt1~, C:;„5 alkoxtosopotf, k&amp;iogésatemk, aano«, C*s aikanoii- és teluormetltesoport köstül vannak kiválasztva), vagy R* és R' a szposszédos nln-ogénatenmal együtt 4-8-œgù teilten vagy- telítetlen heterocikhua képestnek, amely gyűrűjében adott esetben agy vagy löbb nitrogén-, oxigén- vagy kénatotnet tartalmaz a szomszédos teogéttatomoa Ütemben (the 4~8-tagű ítélted vagy·· telítetlen heterodklns adott esetben szubsztítuálva vsa) egy vagy·· két csoporttal amelyek hklroxil-, Cte átetesogort (a C>.$ sBblesoport adott esetben szobszti&amp;tálvs van egy vagy két Mátteteoporttal), Cs.,5 alkoxlesoport, halogéttatenoL dán«-, Cm .alkarunk oxo-, amtek&amp;rbonil-, mono-C^alktlantisókarbonik, dikC^alk&amp;tmmoteboml- és tnfíuormeiilcsoport közül vannak kiválasztva, és a 4-ö-tagé telken vagy telítette hateseiklsis adott esetbe» tartalmaz egy C:,s alkilénesoportot. amely a gyűrűben két kütebüzo szénatomot összeköt) vagy 2'Osa-$~íizaspiro(3.3jhspi-6-ü- vagy ?-oKä'2»azxä5pirn!3.$'jnon'2-iR -csoportot képez,
  3. 3. Az 1 vagy 2. igénypont szerinti ázol-származék vagy ennek győgyszerészetlieg elfogadfeáté sóié, ebül a fenti (1) képletben X' jelentése egyeskötés; XJ jelentése -€;..·$ alkilén- vagy alküéscsapen; és at: Á gyűrő jelentése bemrtegyürü, 6-tagú aromás hsteroesldns (a benzol-gyűrű. é.s a ő-tagű aromás beíeroctkhn. adod esetben soubsanválva van egy vagy két csoporttal, amelyek haloeténaton-ok és Cm alkoxlesopoti közül vannak kiválasztva) vagy 4-8-tagü telített vagy részben telítetlen heteroeiklus« amely egy vagy·· két nstrogénatomot tartalmaz la 4-8-tagú teltet vagy telítetlen heterociklos adott esetben azubmlta&amp;lva. van egy oxtxssoporttai).
  4. 4. Az 1-3. igénypontok bármelyike szériái szol-származék vagy ennek gyogyszerészédleg elfogadható sép, ahol a feszti (Ï) képletben ss A gyűrű jelentése benzol-gyűrű vagy b-tagá aromás betoroetkbis (a beazol-gyürő és a ö-tagó aromáé aeterociklss adott esetben szubsztituálva van egy vagy kát csoporttal, .amelyak balogdnsaomok és 0<o alkmcícsoport közül vannak ki választva).
  5. 5. Az 1-4. igénypontok bármelyike szerinti .te!· származék: vagy· ennék győgysseréssétilég éüégadbátó sála, slio.i a fenti (!) képleten az A gyűrő jelentése benzol- vagy plndm-gyiirü (a benzol- és ti plnáin-gyürn adott eseten szetedifesáte van egy vagy két csoporttal, amelyek halogénatomok és CM alkoxlcsoport közit; vannak kiválasztva). 6, A?. KI igénypontok Mrtneiylke szerinti szol-szánnszék vagy «à gydgyszetósmüeg elfogadható-sé|a, aboi &amp; fend Π) képletben R! jelentése C%^ -altóteseport; R'; jelentess btdxogén&amp;toin; és R'" jelentése fenil· vagy plndli-gyürû (a fend- as a piridifegyürü adott esetben szubsztitoáiYa ven n» y vagy kéi csoporttal, amelyek C\.j alkil-, 0,.$ aikoxscsopnrt, halogénak-n-ok, chao-·, íribuormstii-, dilfeor-netoxh trlfiaöTntetoxfe és C<.í afeiiszulfonil-esopoxt kSsül vannak kiválasztva).
  6. 7. Az I -é. Igénypontok bánselyike -szerinti «Wstmé vagy énnek gyégyszerészeíilsg elfogadható sója, aboi a fenti (I) képletbe® az adott esetben a^feszfenáit axôl-gÿSril, amely az alábbi (¾) képlettel van. leírva, |4. képi}
    «5 az alábbi fül) képlet-csnpöítbsn bemnt&amp;íbtt szerkezetek bármelyikével rendelkezik, rs. kétíl.l
    |II!} ahol tv jelentése hidrogénatom vagy1 ntetllosopori §. Az b-?· igénypontok bármelyike szerint! azol-származák vagy ennek gyégysxtarészabktg »{fogadható-sbja, ahol a fenti (I) képletben. X' jelentése egyetótór, X'jelentése etilén·· vagy nsetilerilén^esoporí; és R* ás R ' a szomszédos nitrogénatotrunai egy&amp;tt 4-8-tag« {»litert vagy telítetlen hefereeskhtst képeznek, amely gyöngében adott esetben egy vagy- több nitrogén-. oxigén- vagy kén&amp;tomoí tartalmas a szomszédos nhrogén&amp;tomos túlmenően (a 4-8-tagn telített vagy· telítetlen heteroctkhss adott esetbe;· szabsztlteSIva van egy vagy két csoporttal, amelyek bidroxiî-, €).> alkütsoport (a €·.< alkilesöpört adott esetben szubsztitaálva van agy vagy két hidroxilesoportt&amp;l), C».j alkosicsopon, halogénatomok, manó-, sllnmoil- és trilhtonne&amp;i--csoport kisxöl vannak kiválásivá, és a 4 -S-tsgö. telített vagy islástlett ketaródklus adott-esethea·· egy €« aikiléncso|Katos. tartalmaz, amely a gyünkben két koidabSsfe szénatomot Összeköt) vagy R-exn-é--az&amp;spirop.3 jisept-d-ií-csoportot képez.
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' -: 4'[2'(mô{fôHa-4 - Π )etj}) fenü} '5-oxo»4-(3»(ô1tonaôtil)fmjI}4«5 «dihidr©» ΐ-Η*Η2,44π»2»Ι«Μ})“Ν- -(P'v0psa-2~i!)ace5as»d; 2-[4-{3~k}6r-4-iîaorfôRii}-i (4-(2-{3-oxia§'&amp;s<4akv3do[3.24i]c4;t-d'ii}propd]ri:f-!]}-'S-i>x«-4:.S-dih!i:ko-4H;--l>2,44na^]04ij-Ní~(prcípa3i-2-ii}&amp;cet:aiTÍ!Íd) 2-(4- ¢4- Huor-3-;aPaxifas;i}~!-{44243-axá-k'a?.sfcí<.lkk>[3.24)c4a84Í)«díj(enö>5-GXö-4J'd5í-káO' ;H--1 ;24kín;-^ok3-in-K-í'propava·;·--sríacpsrnsű; 2-(4-(4-f4JOí-3-a3eíoxlfe!í!)--l--{3-meUíxl-4~[2-(3~ox4-S-'a4sbíc.i.klo(32J]ókí-d"íi)<íd!J(kaiÍ}-'5-öXö-4,5--dikksra- ! H 4,2.4 4π;^κο^3-ί1)-Ν-(ρΓθρ3Λ-·2-ίΙ}δε4Ρΐίΐΐίά( i)oka-8-;3}eadfenO)-4-(3-mstox(f4síl)-3-öXi3'4s3-diSíiídrc··' -íií»l,2,4-íríáoíOÍ-3'ü]-M4prop8«-2~H}8c<rí*tn{á; 2'í4-ii3-kIdí“t-0tíodef}-U>-S-o.<o-'i-(4-p-(puvoháúí-í-íS)<S:tüjfea'.ij}-4,3*d{ydí<:-Uf-k2í4'trÍ33aí5-3-H]-K- -(pï'i>p^-2-:ü)3.ç.s5Îiîni>i; 2-(4-(3^16Μ~ΐ1«όχΓ0κ4}-·5-οχθ'Β·{4-(2-ίρ!ρδπ<ΐ5Χ-14()4ί3]&amp;δΙ1}-4ρ^4Ι^ΰΐθ-ΙΙ4"Ι(2,,4-ίπ83:ο!'341]-Κ--(própají-2>4í)4i;epía-íkk és acetsaaM, !Κ Győ^mrfcéssteány, amely m I-lCb Igénypoatok btedyîke uertel asol-satatókot vagy ennek gyógysserészetiteg elfogadható sóját tartalmam hatósayagkóat
  9. 52, Egy sser hang«) árbeli rendel le-nesság, ssïîongàsos rendeüenesség, ddanfrénia, Abhsîæer kór, Parkinson kór, Hangtinion chorea, tápiáikGK&amp;si reruküenessêg, magasvóroyomás, gymnnr-bdlrendseen besegség, gyógysaerföggőség, epilepszia, agyi miarktas, agy! isehétnia, agy; ödéma, fejsérülés, gyulladás, immusháss&amp;l összefüggő betegség vagy hajhullás kezdésében vagy rnegelöa-isehen történő alkalmazásra, amely sxet ag MO, igénypernek bármelyike ssalru azoMzármazékor vagy ennek gyégyszetészetüeg elfogadható sóját tartalmam hatóanyagként
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