HUE027494T2 - Imidazo[1,2-A]piridin származékok FGFR kináz inhibitorokként terápiában történõ alkalmazásra - Google Patents

Imidazo[1,2-A]piridin származékok FGFR kináz inhibitorokként terápiában történõ alkalmazásra Download PDF

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HUE027494T2
HUE027494T2 HUE10718660A HUE10718660A HUE027494T2 HU E027494 T2 HUE027494 T2 HU E027494T2 HU E10718660 A HUE10718660 A HU E10718660A HU E10718660 A HUE10718660 A HU E10718660A HU E027494 T2 HUE027494 T2 HU E027494T2
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Gordon Saxty
Valerio Berdini
Christopher William Murray
Eddy Jean Edgard Freyne
Yannick Aime Eddy Ligny
Pascal Ghislain Andre Bonnet
Berthold Wroblowski
Alexandra Papanikos
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Astex Therapeutics Ltd
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Claims (8)

  1. IMlBAZO[l,2*A]MRII>IH SZÁRMAZÉKOK ϊβ» KINÁZ INHIBITOROKKÉNT TERÁPIÁBAN TÖRTÉNŐ ALKALMAZÁSRA Szabadalmi igénypontok JL & követed (I) képlet! vegyíilet: ahol
    R! jelentése -NHCON'R4R's vagy vagy ÄB-beteröelklii, ahol a. beterocikli! jelentése íladiazolíí %ágy oxadíazolíi, és ahol a betemelklil csoport opcionálisan szubsztituúlva van egy vagy több (példát! t, 2 vagy 3) által a következők kbzül: halogén, CWaikil, C2-*-aikenii, CS-ó-alkirtii, C^g-eíkloalkíl, C^elkloaíkeníl, -OR*\ -(CH2VO-CUs-iúkik ”.0-(CHB«-ORö, haioC^rálkik haJoCi^alfaaxi, Q.r alkanol, ~~-0. =5. niírb, -(CH?)S-CN, -S-Rd, -SO-Rd, -SOj-Rá, -CÔÉ* -(CRdRVCQOR{, -(CH')^CÖNRdRei &amp;*&amp;&amp;&amp;&amp;* ·40%^ΝRdCORe, ~{CHa)r m^scvr, -(CH2X-NH-Sö2-M&amp;dte* sornyi?, -fCl-í2)s-MRdCOnr, -O-ímik-vagy KCÍfc|-SC)«dle csoportok: R* jelentése C2.4-a.lkoxi, haloCN-4-aikoxi, CM-alkoxi-Cj-j-alkii, cikiobuíoxi, eiklopropoxy, -Mí-Cm^alkil, ^(CM-alkiljj, ^Ci.r^Ikd-'NilCCi^aikik -€j-4-âî* M|C|-4-alkil3^ €:M-alkl-S|^0)rCMw^W vegy -Í(^0)2-Ci-4-alkil csoportok; R3 jelentése -€(-(>)-&amp;’, -OR* vagy egy 5 vagy 6 tag! heterocíklil csoport opcionálisan sznbszíiíuálva egy vagy több (például 1, 2 vagy 3) által a kővetkezők közül: halogén, €V,y-alkii, CS^-alkenil, Cn^-aíkinií, Cvg-cikioalkil, Cj^-elkioalkenil. -OR", "íCHi)a~0-Ci.e-ulkíL -0-(CH>}„-OR8, haloC>.&amp;-alkih haioCw,-aikoxi, Cj.fl-alkanoí, =0. -S, mim, Si(R*k -(CH2}rCN, -S-Rs, -SO-R?, -SO>-Rs. -COR*\ -(CRgRVCOORk, -i CH ' ),-CONRsR". -<CH:k-NR*Rh, -(Ci^VNR^OR”, ~(CBzh~ NRgSOrR\ ~(CIÍ2g-NH-SO7--NR?R\ -OCONR*Rh, oCll2.)5-NRsCOaRh, -CMCíbV CR®Rh-CCIl:2}rOR-; vagy -(CHbVSO»NR*Rh csoportok; RK jelentése Cj^cikloalki csoport opcionálisan szabsz!taàlva a következőkkel: hidroki csoport vagy HR'R”, vagy CWaikil csoport opcionálisan szabszütuálva a kővetkezőkkéI: hidroxh csoport vagy NR’R”; &amp; és R” közöl mindegyik jelentésé: egymástól független!! hidrogén, Ct^-iáíkM csoport: vágy W és R” együttesen a nitrogénnel, amelyhez azok kapcsolódnak, egy telített heierociklusi képeseinek fc kovetkézök közül választva; piperjtjinií, piperaziatl, morfolinil vagy uomorfoünü; R4 ás E5 közöl rmndegyik jelentése egymástól függetlenül hidrogén:, C^-álMí, áikeni!, C^-alkinil, Cv^-cíkloalkíL C^-cikioalkenik €j,ő~aikanot, .McC^-aiküv RSR*, -ÍCHS-COOR^, -íCHaVO-íCHsVOH, -(CH -(GMjG-Ö-ariL H[CH2)n-heterociklll vagy -(CH2)«~0-heterocikiiJ csoport, ahol a nevezeti- Gpe-dlkll, CWalkenií, Cs^-aikinil, C.^-cikloalki), Cs^-cikloalkenil, aril ás heíeroeikiil csoportok opcionálisai szufoutituálhaiék egy vagy több (például 1, .2 vagy 3) Rp csoport ittak Rp jelentése halogén, Cj-e-alki!, C2..<,-alkeni). C2.í>-ulkinil, C^-cikloaiki!, Qes-eikloalkeníl, -OR!\ ~(CHri;rO-Cu>-alkil, -0-tCí-í>.t,,-0Rk ha1oCi.f,-alkü, haloCj-6-alkoxi. C{ ,,-alkanoi, =0, ~S, nitro, SiíRrtí. -íCIlA-GN. -S-R-, -SO-Rrt ~SO;~Rs, <€ÖR8, ~(CR8R“i<-COOR\ -{CH>)cCONRsR!i, 4CH2X-NR8R\ aCl-h k-N R*COR\ 4Clhk^SÜ2‘R\ -(CH2X-Nl-l-S02>NR?Rh, -OCONRsRh, -(CH2k-NR^CCkRó -O-ÇH:^-CR8Rh-(CH?.)t“ORîc vagy ~íCH2)s-SO;NR^R!; csoportok; Re, Rc ás Rr jelentése: egymástól függetlenül hidrogén. Cjí-alki!, C^ÄliÄ Qtér alkinil, Ct.(,-alkaool. hidroxi, Cj..s-alkoxi. halo€Walkil, -CO-(€H;k~Cí^aíhoxi Cm-ciki (ml ki). C;;.x-dkioatke?iil csoportok; R8, Rh és Rk jelentése egymástól függetlenül hidrogén, CWalkil. C>.f-alkeni!. C2.<$~ alkinií, Cj.«-aikarmí, -COOCj^-alfcíi, hidroxi, Cu,·-alkoxi, haioCWalkü, -CO-CCHi}«-C}.ft~aíkoxí, C: .6-alklt-amínó^, Ce.x-cikloalkii, C.vg-cikloalkenil csoportok; rttiés a jelentése egymástál fliggetieril! egy egész szám 1-tol 4-ig; s és t .jelente egymástól függetlenül egy egész szám ö-től 4-ig; vagy annak égy gyógyászatiiag elfogadható síp* tstüpmerje, IPoxidja vagy szoivátja.
  2. 2. Vegyület az I. igénypont szerint, ahol R1 jelentése -NIíGÖNR^R5, piéidául -N HCONHCí-kCFj, -NHCONHCH2CH;, vagy NiCONHClííaCHiOGja.
  3. 3. Vegyidet az előző igénypontok bármelyike szerint, ahol: Ra jelentése Cg^-aíkoxi, Ci-r alkoxi-Cî-4-aikiÎ, cikíobutoxi, -Ni?-CV-4-rtíkil, ~Cj.4-aÍk*l-IÍfí(iCM“aík8| vagy ~Ci_4-aîki|>-N(C i..i~alksl)j. csoportok,
  4. 4. Vegyidét a 3, igénypont szerint, ahol R" jelentése Cea-alfcoxi, eikiobníoxi vagy Ct** alkoxí-ÖjarafkR esöpörtok, példán! -O-CHrCÍ-R vagy -0-0-1(0¾)¾ vágy-CM2-0-0¾.
  5. 5. Vegyiléi az előző igénypontok bármelyike szerint, ahol Rr jelentésé -€(~0)-R\ -OR* vágy eg> hetctocikÜl csoport ti következők közül választva: tiadáizőlil, oxadiazoiií, ímidazoll, piperidmíl, píridinil és pirimaiinil. ahol a heterociklíl csoport opcionálisan szubsztituáíva van egy vagy több által, például egy vagy kettő által, a kővetkezők közül; halogén, C,.6-alkik haloCj.6>aîkÜ, -(CH2),-NR*Rh. C^atatol vagy -(CR^GDO^ csoportok.
  6. 6. Vegyület az 1. igénypont szerint, ahol R! jelentése NHCÖMR4R5 es Ë? jelentése hidrogén és R5 jelentése haloCi^-alkü csoport és Rs jelentése Cja-álkoxi csoport és R~ jelentése pirimídinil, piridirái. tiadiazolii vagy oxadiazoül.ahol a nevezett gyűrűk közül mindegyik opcionálisan szubsztituáiva van,
  7. 7. Vegyület a 6. igénypont szerint, ahol a girimidinll, tâdiazoli vagy oxadiazoil iszubsztituáJva van egy vagy több által, például egy vagy kettő által, a következők közül: -G%, ,F, Glri és-^¾. &amp; hegyidet μ 1. igénypont szerint, ahol E^Jèleûtêæ Ml:IC()NR4Rs és Rf jelentése hidrogén és iï5 jelentése haloC^alkil csoport és jelentése C^-aiko** csoport és R~ jelentése egy S vagy b tagé opy<öMtsäÄ\SMliiSigÄÄWea3©iÄ:csoport,: Sk Vegyidet a 8. Igénypont szerint, ahol a heterociklil csoport opcionálisain sznbszrituálva van egy vagy több által:, például egy vagy kettő által, a Mvelkezők közül: halogén, Ci-e alföld haloÓ^-alkU, ~CG3I2)S~NR^ C^-alkanol vagy -CCRsRh)COORfc csoportok, péliM egy vagy kettő által a következők közül: ··€%, ~i, -€Fs és ~NFk. 10«. Vegyületaz Ugénypont szerint, ahol; R! jelentése ahol|eleníése hidrogén és R" jelentése hidrogén, €*#· alkil csoport opcionálisan szübsztteiva egy vagy több R'; csoporttal; R;i jelentése Cj^-alköfö, Cv.ràlkôxiÆi-fjvÂil, eikiobutoxi, -NH-Cj-4-alkií, -C M-alkií-NtCi-ralkik vagy -€5.4ΌΐΚϋ-ΝΗ(€;.4-δΜΙ) νκορο«<Λ; és R* jelentése ~C(~0)~R\ -0-Rx vagy egy heterociklil csoport a következők közül választva: tiadiazoül, öxadiazobl, imídazoíl, píperidínll, phidiníl és pirimidisll, ahol a heteroerkhl csoport opcionálisan szubsztiiuálva van egy vagy több által, például egy vagy kettő Utal,: a következők közül: halogén, C^-alRil, haloCh^alföl, hjCIiár NR%fe; a,.ralkanol vagy d€R8Rh)COORk csoportok; Ri? jelentése halogén vagy OR8; lejelentése hidrogén*. R* jelentése Cj.ö-cikíoaiföl csoport vagy R* jelentése Q^-alfcii csoport hldroxil csoporttal szubsztituálva; és Rk R'J és Rv jelentése egymástól Függetlenül a kővetkezők közti! van választva; hidrogén vagy C}.{,-alkll csoport, I I, Vegyület az h igénypont szerint, amely egy vegytlet a következők kozni választva;
  8. 12. Vegyöiet uz L-töl 1i.-ig igénypontok bármelyike szerint vagy annak egy gyógyászati lag elfogadható sola vagy szoivátja. készítmény, amely tartótól. e|y az L~tâi 12.-ig Igiivpeniok bámtelyike szerinti (1| képleíü vegyü letet. •l4„ Yegyüfct az 1.-tol 12.-ig igénypontok bármelyike szerint, dl terápiában íMé0 alkalmazásba, vagy di) egy betegségnek vagy betegségi állapotnak a megelőzésében vagy kezelésében »énő alkalmazási«, amely a következek közöl van választva: nnelőma multiplex, mii^oprolifèrativ rendellenességek, endömetriális rák, prosztatarák, hélppSk* tüdőrák, petefészek!#» emlőrák, gyomorrák, köiorektälis rák (vastag“ és végbéfrák) és szájüregi lapbámsejíes kareinómá, vagy (ii|) ráknak a: megelőzésében vagy kezelésében történő alkalmazásra. II. Egy a? 1 .-tői !2.-ig igénypontok bármelyike szerinti vegyüM alkalmazása egy gyógyszernek az előállítása céljából, amely egy ráknak a megelőzésére vagy kezelésére szolgák
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WO2010119285A1 (en) 2010-10-21
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CA2757326A1 (en) 2010-10-21
AU2010238290B2 (en) 2015-12-17
US8722687B2 (en) 2014-05-13
AU2010238290A1 (en) 2011-12-08
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DK2419428T3 (en) 2015-08-10
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