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HUE035295T2 - A Poli(ADP-ribóz)-polimeráz (PARP) dihidro-pirido-ftalazinon inhibitorai - Google Patents

A Poli(ADP-ribóz)-polimeráz (PARP) dihidro-pirido-ftalazinon inhibitorai Download PDF

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Publication number
HUE035295T2
HUE035295T2 HUE14154664A HUE14154664A HUE035295T2 HU E035295 T2 HUE035295 T2 HU E035295T2 HU E14154664 A HUE14154664 A HU E14154664A HU E14154664 A HUE14154664 A HU E14154664A HU E035295 T2 HUE035295 T2 HU E035295T2
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HU
Hungary
Prior art keywords
phenyl
phthalazin
dihydro
pyrido
methyl
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Application number
HUE14154664A
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English (en)
Inventor
Bing Wang
Daniel Chu
Original Assignee
Medivation Technologies Inc
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Publication date
Application filed by Medivation Technologies Inc filed Critical Medivation Technologies Inc
Publication of HUE035295T2 publication Critical patent/HUE035295T2/hu

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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
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    • 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
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Claims (4)

  1. A ΡΟΙί(ΑΟΡ4?ΙδΟ2ρΡΟΙΙΜΕΡΑ2 (PARR; OiHIBPO-PiPäDO-PTALAZiNöhi iNHÎBlTORAi SZABAüALMî IGÉNYPONTOK
    1. Az alábbi áitalános képlettel jeltefnezhetó vegyöleb
    vagy armek. agy -gyógyászaííísg «Ifogadhafô .sója vagy «zoiváíja, 2. A 1, igénypont szsnt dl vegyütst. áhöl a vagyülat 0; ίδΡ,θΒ’-δ'ΡίυοΓ-β-ίΑ.ήϋΟΓ^η^'θ-ίΙ-ΐΡδΙϋ’'’»/·/"'! ,2;4-t!ÍíiZo!-ö’iij'3;3-dih:<iro-2H-pifldo[4,3,2'de:ftáiazfo"3{7M"On vagy ennek agy gyégyászaslag elfogadható sója; vagy (it) {8δ!δ^}>§-Γΐυ0Γ*β'(4-?ΚϊόΗ0ΓίΙΓί'9^Ί'^©Ιί?-ί/ϊ^>2!4·-ΐ0320^δ"Η/*δ:δ':€ίί^^ΐΓ0>2ΗηρίΗ00[4ί3,2^0}^ΐ0?.ίή--3(?Η}<·οή vagy ennek agy oyégyászatiiag elfogadható sója. 3 Az 1 igénypont szénné vegyelek ahes a vegymet {aSfoR}-5-éíseí'S-í4-ánorfonii;G'Ít-n5et:ntA'1,2.naf:azoná-fo-é.ó' dihldro-2H-pindo[4,3.2-delftälaztri'3{?H}»on vagy ennek egy gyógyászatilag elfogadható sója.
  2. 4. Gyógyászati kószíanóny, amely tartalmazza az 1. Igénypont szenntk sióból általános képlettel jeliemezbető vegyöietek
    vagy ennek egy gyógyászatilag eifogsöható sósát vagy gyogyaszahfog elfogadható szolvátját, valamint agy gyógyászatilag elfogadható hordozók segédanyagok kötőanyagét vegy oidószatt ó. Á 4, igénypont szerinti gyógyászati készítmény. ahol a vegyúiet g} (0R,SS;->&amp;->é|po^844"ttóasíaniipáaj-metlk ^ló^áflszokmiiASj.őlniófö-kákóirídbjA jJ-detááiazin^tZHjfon vagy ennek egy gyógyészstííag elfogadható sója; vagy {üt 5δ5.δΑ}·-5'ΡΐοοΓ'δ-ί4ΑΙηβΓίοηΙΙ;-§-(ηηηηίΐηΐΗ.·ΐ,?,4όη5ζοΙ·'0-ίΐ)-3:2-οΙ0!θη;'?ήί-ρ!ΓΐοοΙ4,3A-deiftaiazinfotZHj-on vagy ennek egy gyógyáSzstifog elfogadható sója.
  3. 6. Az 5, Igénypont szehntí készítmény; ahol a végyüfot (§Si8R)'S-kpOi'-'8A4mppitsn||}~§AAf'iietlkW'i;2,4foiazokSdS}^.fo éfoidrô-2Hfoiridofo,3.2mejftétszfo-3{?H)fon vagy ennek égy gyègyè&amp;zatllgg elfogadható sója. ?.· A 4, vágy .§, igénypont szerinti készítmény. ahöi â; fô-szîôbêny orális,. Oskkéüs. sztíbiingváiis. intrevénès, .InhÄfos, nazáfis. fojekeiós, helyi, ezéniéexeti, rgktáíis. .parsnteíális vagy transzdermáiis bevitelre alkeimes. A 7 igénypont szerinti készítmény, ahol s készítmény eratis oevdeire aíkaimas. S. A S. igénypónt szerint; készitmeny, she; sz orális adagotásó kàszitmérty egységrfozisú gyógyszgríerme, zhei adett esetben sz ogyeégdézis egy tabletta. por, piruia, drazsé, kapszula, folyadék, gél, szirup, wir. sörö szuszperizlo vagy szeszpenzié. 10. n * igv'-gm : s?t- st \.e, ;.z ogv»,\ce. », gvegtszerte;ms »om.afoU 1 e» kotjbc , ; \ i-.'zcr mennyiséget fe;lalmaz a veoyplotbét vagy annak gyógyaszafilág elfogádhstó sójából vagy szeiváháPéi 1 1, A 8 igénypont szerinti készítmény, phot ez m-alls Pevdelro alkalmas.készítmény. jij kêruibeks 0 01 es koróibgiul 2,5mgíkg vegyulefet vagy annak gyogyaszaiilag elfogadható sóját vagy szolváíjét tertairnszó dózisban van. seri megiéíg; a beedheto napi ögzlsnak: vagy (il) kérüibeíd; δ,δ és kérüíbetöí WO mg vegyófotef vagy annak gyógyászaólsg elfogadható sóját vagy szeivéfiét tartalmazó oázisban van amit adott esetben napi fogieljebb négy adagra efosztott soztsban vagy rotate formában tenet beadm
  4. 12, Az 1-3, igénypontok bárrnelylka szerinti vágyóiét vagy a foil. igénypanfok bármelyike szerinti készítmény a rák kezeiésl médszeráben veié folhesznélásre. 13, A 12. Igénypont szerinti felhasználásé vegyiket vagy készítmény. ahoi a módszer abban áll, négy s vegysiietsi vagy a készítményt ogyldejőieg vagy egymást követben juttattak be fontsaié sugárzás, egy vagy több kemoterápiás azét vágy ezek kombinációja mellett, 14, A 12, igénypont szerinti feihasznaiasé vágyóiét vagy készítmény, ahoi a rák típusa az alábbiak közei válesztefo amforák; petefészekrák, endomelrtomdumpr, méhnyskrák, tüdőrák, prosztatarák, hasnyairnirigyrak, bemstoiéglai daganat, íeukémte, vastágbélrák, Péfoagánsk giiobiestoniá, iimfoma és melanoms iá, A 14. igénypont szerinti fefoasznáiásé: vegyetek vagy készítmény, ahoi a rak típusa az alábbiak közói választott; emlőrák, petefeszekräk, tüdőrák, prosztatarák, hashyáimirigyfák, vastagbéirák és melanoma. W. A 13, igénypont szénné feinasznaiasú vagyaiét vagy keszumony, aboi az egv vagy febb kemefompiás szer egymásfoi főggétjenói (i) áz alábbiak közei válásztott; afemfezumob, grzsnthoxid, pegiiáit aszparagloáz, nem pegiiáit aszporaginéz, bevamzumab. esfeximab, ospiaiin. eladóéin. özunotubscínfeoxorubíoínádaíobímf! mnoteoan, ffodersbin. 5-ttnonjrees, gemtuzumao, metotrexét Paciitsimbfo texoi. temczofomid. t;oguanin. egy antiosztrogen hormonanaiég. egy snt.anöfogen bormonsnaibg, egy gonadotropin'f&amp;iszabadiio hormongnafog. alfa interferon, busuilan, mssplialan, meehleretnamin, tretinoin, irínotooart, topoteoan. ggümőmb, Imaflntb, stfopttrlnel, fiigrastlm, gramseifonfondansetronfpaienosstiOnds dronsbinok vagy ίίί) egy afkiiâiàsM vagy egy topoisomaráa-l inhibitor, ahoi adott esetben ez aiklláíöszsr vagy s iopoizomeráz-·; ínhibrtöt meííí-meténszuitenát, lemozteomld. riaearbazin (OTIC). Tepoteoan, ínnotésáh, Rehíísoán, Bzeteoen. Lurjetédsn, Gáaatecsn. Diílomoiecan ítmrrmkamptoteclnek), egy ?-szubsztifeái{ nem-sllateoan, a z-sziííl-cemptothecin. BMP 1350 vsgy XR 11576/MLN XX, vagy öü) innotéeen, osspiatin vagy teozslomkt ír. A Ί2·1δ. igénypontok szerint; telhaszuáiásá vsgyülst vagy készítmény. ahoi s daganatban íiter-yes a DNS-kettösszál töréseinek sDSB- Doubte strand Break) nomcteg fek*obtoá<?óthggo |HR - Homologous Reoombinadenj javitasi útvonala 18. A,1 ?. igénypont szét inti lelhaszrsálásö vegyólet vagy készítmény. ahol a rák egy vagy több olyan rákos sejtet tartalmaz, {B amelynek a normális sejtekhez késest ősökként vagy megszűnt a képessége a ÖMS DSB HP, mechanizmus éltek kijavítására, ahoi e rákos sejtek értett esetben BRCA1- vagy 8RCA2-hiányos íenoiipussal rendelkeznek, shoi a rákos sejtek ezentéiéi adott esetben BRCA1 - vagy 3RCA2-niányeáák is: vagy (ti) amely hiányos s DNS DSB HR mscbanlzmdé általi javításában résztvevő proteinekben, ahol a rákos sejtek adott esetben hiányosak ez alábbiakban- ATM, Racist., Rsd52, RsdbA Radőö. MRE11. N8S1. XRCCX XRCC3, oASl. RPA. CtíPésMBC. 13, A12. igsnygont szerint; ieihaeználásá vegykist vagy készitmény, shot a kezeiendö stony hetsroz-göts a következőkre: 11} mteroXXS \Ηχ( ""'B t ste i -m aim >. pé k<'t\0i,e"éi v > lő gé'O' t , jl; j muteclö s SRCAl-oert éstesgy BRCA2-ben. 23. A12-18. Igénypontok szerinti telhasználásá vegyiket vagy készítmény, ahol a daganat: (i) hiányos a hibás bázíspárosodás (mismatch) DNS-javííási élvonalban, ahol adott esetben a rákos sejtek hiányosak MutS-ben, MatH-bon és MutLhem vagy (ii) a ősökként vagy károsodott BMS-jsvifö útvonalak következtében mikroszeteiirte instabilitást mutat; Vágy (Ili) a csökkent vagy károsodott DNS-javltó útvonalak következtében genornrnsíábiiitást mutât.
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