HUE028418T2 - 3-Heteroaroilamino-propionsav-származékok és alkalmazásuk gyógyszerként - Google Patents

3-Heteroaroilamino-propionsav-származékok és alkalmazásuk gyógyszerként Download PDF

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Publication number
HUE028418T2
HUE028418T2 HUE12738473A HUE12738473A HUE028418T2 HU E028418 T2 HUE028418 T2 HU E028418T2 HU E12738473 A HUE12738473 A HU E12738473A HU E12738473 A HUE12738473 A HU E12738473A HU E028418 T2 HUE028418 T2 HU E028418T2
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Hungary
Prior art keywords
phenyl
amino
carbonyl
alkyl
oxazole
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HUE12738473A
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English (en)
Inventor
Sven Ruf
Josef Pernerstorfer
Thorsten Sadowski
Georg Horstick
Herman Schreuder
Christian Buning
Klaus Wirth
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Sanofi Sa
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Publication of HUE028418T2 publication Critical patent/HUE028418T2/hu

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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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Claims (2)

  1. is :pJKALMA^^K múGvsmmÉm SzafeMaloó sgéssypoaiok y, {0képíétő vegyólöt bármely s^^oixómar&íbaoáiMsss vagy sztetmkzőniérei bármely srásyá; kevereké' sek Ibnsájábíso vagy tmiolőgiásas elfogadható sója vagy ezek bámrelyik&ssk
    í" sbPbM Jsleátése1 a ikőveíkszSkblt: álló ésőpttből választott:
    0 fsleotése E'^Ö'-C-CO)'·; %* jaiéátése á kővetkezőkből állő esrgtöílből váím&amp;^Mföogési, h&amp;logéo* t£y€&amp;}-alfók CF-.. (CyOfHákío&amp;k :^1½¾¾¾ ^Cs®js·., J-S'-'O» (CrC^álkU-O-y {<2í^ptíklFS{0}»- és NO·; also! a éneke a kővetkezőkből álíb csoisörtbél; yibwiöií egész szám: 0, 1, 2 és 3¾ :K'' jdeatése a kővetkezőkből álló csoportból vákssztbtt; Ikárogóo, balogén, {ICrC^-siisil, OFs, CCV-QHIMI 0‘,(Cí-C\}'^kH“S(OVis nc-i ll:i' jelestése Rss R!Í jelentése Ar; R30 jelentésé a kővetfciÉfcbŐi álló csoportból választóit: 02s~l2#«-elklosild1 is E^-CJÍja», sbstu értéke akőv vétkeikből álló csoprlMl választott egész szám; 8, ÍS: 2 # 3; R3^ yslptése a kővetkeáikbŐl ál# csoportból vtáfes2ÉÉÖé|&amp;^á# «*«*»&amp;?< ő tagé vagy δ lap moooóiábóos Rétezeoiklua, amely a következőkből álló esopoítbos vilsskíSíb: agy, kettő vagy bárom, azooos vagy kpóa-bóp gyóró^teorosrpmót tanalmaz: mtzopa, ovlgéáéálpi: Is szésátotóöó keresztéi kötődik, alsói a leáll ós a featorocsklos adóit esetben szobsztitoált a következőkből álló csoportból választott egy vagy több, azonos vagy kóllöbóxd simbsxtitsísiasol:- hsíögép, (CrC&amp;Hlkil, (GrCvWtkioaisiyHÖ·» 0%*iC«)»d:MF£h Ό* -CHr€K d>-€iyö·, (CrC*)-aíkH-S(0)m^ H:íN-S{0}r, {Ct^)-aikil-NH-S(Ö)r, dl((Cr^áÍkll)N* -Stö>r, JfcNA, (C5~Cs)~a.íktl-Νϊί-, dKCCrQFslklííbK {C-CbFalkíkC(í:i)-KH^ {CrCíM&amp;lÉ-St^^H- és NO; Rsö jelentése a következőkből álló csoportból választott: bldrogéa és (Cs-C^-alkil; Rí0 jelentése a következőkből álló csoportból választóit: hidrogén, (C?~CökaíkÜ, HÖ- ős (Cy€*)“aiky»0«i BT0 (Cy€s}~&amp;ikil; Rí! jelentése hidrogén; Ar jelentése bármelyik egyéb Árxtsoprttől logptlcpl a PveikPŐkbői álló csoportból választott: ieoil és aromás, 5 tagé vagy 6 tagú mosiodklvsos bemmdklos, amely a kővetkezőkből ál lő csoportból választott agy, kenő vagy bároán azonos vagy külöabőző györtMxdemstonxot tartalmaz: nitrogésp oxigén és kés; és szénatooron kérésztől kősőóife, altéba leáll és a heserociklus adón esetben szöbsztíbsálí a kővetkezőkből:ál~ id csoportból válassz ogy yggy pib, aaseaos vagy különbőzé saaibmteetmeb fesksgén, (C5-C^aJM, |C| ·0*)<*Μ«Κ -Q-CHj-O-. «Ηϊ-CHrCK -O-CTj-CK {CrQl-aikíbSKO},,-, H3H-S(O}r,0F? és NC-; mindegyik st értéke atökbl m-tól tbggeflenül a kSvetkezb egész. számok bármelyike; ö, 1 vsgy 2; ahol: val&amp;memm éijteaikB^csöpön egymástól ikggeíletitl adott ésetbéts a kovefkezókbó! álló csoportból válasz tort egy vsgy tPb* «ssonos vagy külöóPP aautótetissei szubszötuákc fluor és aM egymástól és bármely egyéb s^bsMmssstdi tóggeíleabl valamennyi CfelJir. export adott esetben egy vagy tóbb Ibör Spbszfiúieakse! szsibsKtígtált, 2, m 1 igénypont mxmtii §0.Mphm vegyidet bátraety s«eoizom^ tormájában vagy sztereo-izommá bfeatíy atányá keveréke f|m5s|ábam vagy nzkdégslsao eibgadbató síp vagy ezek báísneiyikéoek fiziológiásáé eiíog&amp;dhaté szoMáJa, aboí
    i* jelentése a .következókbif álló csog^pbváíaskrotk hidrogén, balogén, (CrC^-áÖdk CBy 0%Q}'ó8db Φ- és Nt\
  2. 3. Az 1. vagy 2, igénypont szeriek (f? kép\M vb^yöM tonnájában vagy smméM®msi. fe&amp;mety keveréke fentíáj^aey^gy ílaiológiásaa elfogadható sági vagy1 essek btoslyi*· kének fkdológiás&amp;o elfogadható szoivátja, alsói #* jelentése R^-CJV, ahol a értéke 8 vagy R® jelentése a kivetkezőkből álló exportból választod: feni és ssmsnás, S tagé vagy 6 Sági Moasv;É!íiSik bsíétseíkiüs, smety a kévéiké zék bej álló csoportból válasz®*!: egy, ketté vagy bároat, meoos vagy Mfc PP gynrii -herery&amp;ioíoóí: birsai-iiaz; nitrogén, oxigén és Ma; és szénatomon Retesztől kiMóik sbeá s &amp;sisi ésaketerocikius adóst esetben sznbszHmáU a következőkből ói*ó csoportból választod: egf'vag^ tóbfe, ms vagy kölöaböző szabsztimeoasei; balogén, -CHj-Ο-, -Ö-ÖFrO-, {Ci^j-altól-SÍPV, HiN-S(%y (€j-€*}-aM-NH-$(Ö)r> áp^Cg^!)N« ~M®br* Η*κ^ i€r€Mkifci}~NH;·, di{(£rC*>~alkiI)N-. (Cír€paiy^SP)rMH- és nc~; R4* jelentése hiíbogéa, 4» A® i-3, sgéaypoatbk bármalyike szeri®!, |f) képieti vegyidet bármely ss^oi^at^'fip^áte vagy mtstmummmi bánsély iaranyó teveriM lö«»á|iSb&amp;8, vagy üzioiógiásaB dtógádhatő sója vágy ezek bskr K-elyikének riziolégiásan elfogadható szolváljá, ahol :1s0 i jelentése hidrogén; R** jelentése hidrogén. &amp; Az 14 fgéaypoaiök bármelyike szerinti, (I) Mpleii végűiét bámsely Sktsreolsssasre formáikban vagy mai^fltfp^bánaely árápó keveréke formájában, vagy ikiöiogláaáa elfögsábató sója vagy egek b<bv mslyskásfok föitóógiásan elfogadható sxblfo|3ja5 ahol 8P Jgfcatóae Rs-CAs-> ahol h értéke 6j: BP jsfeotése l«&amp;og«?n S. Az 1-5. Igénypontok bárnmlylka szermlr, (I) képíofo Wgyüteí Mmsely saSareoizuatere formájában vagy satómolxometei bármely aráoyh keystóte formájába»,. vagy ftkábglfoaa elfogyható sája vágy e®ok Mr~: melylM^k imiológiásan elfogadható *foiyá|a, ahol a v^eM:*||#vete#k-kdyi vslaxstótó S-cíkfoheáilo-^Smielil-S-foaik^ááöl^'kajlKimlj'amm^iipxopjfoífok 3-r(5mnfoi»2d^jlmxaáoM'karboRÍjmmmoj-4-featl'yajssy (5}4-'CCS-\Oáíhh2-feaihoxaeoh4<-karfoa>li>;mxioo]'3-o4ofov|?B5glfo5sav {S)4H2'Baor"fom1)-3-l(§mmlfo2-foailmxaxoM-ketó<foÍHa»5tó|'ptóBfonsáv íS)-3‘(3“fia«»*tó1^3K5~metíW»^8isl-oxazol>4«k!arfeoaöl“aisa^jk^fáossav C$>3«(4~fí«<^|M^3*R5-myi4'feRatóxaKoM«kasb£aál)«»ajae|>pöj)K^8»y (Sr-3'l[2-(^fomf^tóollh$*m«ökas8áol'4-'ka{lKjmlj-amfoö|-3~fohlgtóplöósav (S>-:h((5~k;ogmpíl-'2^fotólmxaa<fo4nkátímxál)-amtóo]-3^efolim^foasav {S!-:>44metóxl"fotó|-3~||5-m«l|;##tólmxaao1-4-kafo6aB|mmtóo|-|m^tó»sa¥ v S)' :> - ΐ 43-1(5-ΪΪΪ0Ϊ l!|y 2-ífejss f-£ss«»»l ~4~karfeé^si>^^m3^j|^P^P lS}~3'í[2-C2-iha5^foálÍj“Sm5eXíl-osaaölr44saíható!j-sahoo}”3^hvtóíik}5tó5Sií!sxsav {SV343»k^-feyh3*[(!^metH«2“fyI;iiapzöl*4-kyHn»0'ajá|i8si|i*^yp^yáy Cl|íi3*lf2'{2-llaor-fa3iil.>-5-n»«ül"Oxa«)lr4»‘lSMlíoy]-aju«Be| 4-&amp;tüfo4pav {S)-3*{[2*{2'i1«or*fonii}'5-metihosasoi~4-ka!b^!i||]-aa^Í;'3>'tel-'^sa.v {b)-M2*yór-fotólh34í5-®«tü-2-fmil-<»áa^1'4^ymaü)HSÉdao||pépioö^v: {3<ikl<djexil-3»i(5-fooB?«^il“2-fetól-<)xa^Í^|yb<^Ü)^ú^|p^tópsav <SV 3-(2-fliK!r»f«5.ü}-3-1 l2^4luor-feil)-5*itói^«ÉtóM*kiÉtó|^iao| -psépmísm (S}-S<3-f1aor»foaii)'3-(p-{2'ílm>r"tóml.B5mmuk-<)kaáoH“ka!footólÍ~anumí)~p®|É«^ iS)vj-<4"na<a-^il)'3"(i242”fmar”l«ail)'-5'arRtólmkaáM-4-kátóöM:lrámfoo}-p(>iskífoak 3-[(542<φ«!^Ι^2?^04οχ«^ί#^^ιΰΙ)«8»8ίο]·Φ^ί^^ί?' {S}~3-{24foor4áall)--3PX5axopmp0-24.lox!lK«aáol44arlx):fiü)-arO!ra>fpropíoasav |B;k3*(4kiaor4sm31>34{S4aos^^ S-íS-klóO'foöílj'S-lp^üara-^haxIjiS-metii-oxaaokfokafoomli^^sfooj^mpfosáav {S)-3(4-klér':^olr3-|[24243aor4«tó}-Saxsetífo>xaaoh4-karbothlj'a5umo)-propkaxsav (S)~3~{(54ao|5mgW'-foa!hoxa^fo44íatóooil)-asshiok3vp..íseí(>xófom3>'gmpkÉssy (SV3423-djSöetóks-foül)'-3-gPmeílB2-foslhoxaaol44eboni0'«míífoj*ps^psohsay J^^ötóM^MmS^-hilla^iÉik'Oxaaol^k^^ÉI-sai^slip^joi^av {S^l^^ikfomfoailj-S^CS-fnyhA'fomkssasol-^^mdmml^s^lnojrproplonsay CSH4(2*tó1r-5^ftó<srmdü^á^Mefe^«t|pyrmoj-3^folü*pfs^liPP' iS)“S<?-flaor'íeiM|'3“Cí2^&amp;ia<S%í^ös?«Í-oxsxoM4cárl>0öÍ>-8mfftol-'pöpo»ss^ (Sy-3- I i -.M 3-6ífíuorm^|toíl>p^í»»«av' (S)'3^|!2-#”i»orfetól~5-p&amp;tü'OXssöH^|k%ot53lj-ím}íSö}*3-(44nfí«onneíí&amp;5Í}^í^ksssíSV {S^3434cl#-f^áKt«KÍ^^M^tóÉ^jtl^^8Í^“karfK»aiJ>8minoj-ísropio«s»v' tS>“SHper^fe8i^3*[P*l^?5-írsíkj0sta^l^áíii^M*kart>onil)*aminol-píopíOö^ |S}-3-(Ss3-^l<3í-refti; ^-[(Sdaopo^psi'Menii-rtta&amp;R'd-karbonURaminoj'-propteosav :<S>3>(i2,4«^M#-f<mil^3'[{5-i^o|κ:ΛpU··^ima'<Sii^i-4-kar¾^)s«ía^o^'pnφksa8»? |S)J‘C|í3"íiiS8&amp;;xi-fémlh34i3~&amp;»Ü~S-mO«<Ín»e}i1'<sppl>4~&amp;8rboaií}~ató^-pK>p5055'5^' {SP^S^Mtei^lp^Pf'^^i^^uofm^l-oxs^W^B^oajl^aaMa&amp;l^i^iossay (S5“3-'ps4--dikló^fei1|-3-Í2'&amp;M4-tóp5Kin»eH!'OxápÍ^karboisil)~Mm^^pötsoíissv; ?, Mjárás 1-6. tgéppetttok bármelyike mríatí, 0) képletS yegyölet vap ágeigiásj»* ejlbgsdhmé séja vagy «aekfescilögsássíí el&amp;gsíteóssöíyapg «Idlllkásétt, amely magáimé j^Jflfja (Ii> ké|deth végydlet magák miásáí (Ili) képleté vepidetM,
    $ m i ahol &amp; 00 a (UI) képletben s Hk G», R% Kx\ &amp;%, ft R5*- és í^esöprí jelentése u (I.) képiem vegyft-kaséi meglmimozmt, és m>n |#ft*· ihokems escportsk jelen lehetnek védett femlban vagy pnekuraor esogort formájában, és a 00 képleíű vegySksben a I-csoport jelentés* HO-, {CiRdk-alkihO- vagy halogén. 8. te I-d. igénypontok feárttióiyiks széttört, (íj kepleri vegyidet vagy feiotegllsas éiíbgadhatö sója vagy estek fiziológiásán elfogadható szolváija gyógyszerként tOrténö alkalmazásra. §. gyógyászai késslttöény. amely legalább <^:t*&amp;-3^ypo»Kfe íÉ^Üyte^PÉÖ* 0} képleté vegyit-tem tartalmaz vagy figyégíásan eJlhgadhstó sóját vsp ezek bánnélyíkénefe feiOlógiásas elfogadható aMvátjáí tMsimmfog és ^jptottl%'«|fog^lbatdiiÉe^#rtate*s>. Iá te i«4 ígénypóittek hárfiselyie szerinti, p lépleth vegyidül vagy izioíógmmn elfogadható adja vagy ezek bármelyikének dzfofogiásan elfogadható saolvá|a íáM(»aaása salve!é^lens% pásgásos sxlvelég-tnköség,Jacdíomíopáha, rolokardláiís ittforktes, hálfep&amp;í. áÉsms; 'ted»rh|^étMÍ8, maps vémpmás, atermszkierózls, pmfértás artériás g^#6^|,:irpmpí^^!í|^sépé: kezelésére, ödéma, trombózis, reumás artóttse, osateoarttittss, veseelégtelenség, dsmás ttbrózik, krónikus kőrg-Kőről, krónikás obslrukílv títóóijetepeg, asztma, iinmshbempég, cutoi^^éf p§vÓdm#p8t: Síw^to W tagság, ijáalom. isskémlás vagy ronertbziós károsodás vagy nemxxiegeserativ betegség késelésére vagy Ipmíoprötekciói'a vagy vsseprotekeióra vagy dlnretikdniként legyedttií vagy dmretiknmmni tfoténö: egyőttss kezelési szolgáló pépszer előállítására.
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