HUE033177T2 - Pirazin karboxamid vegyület - Google Patents

Pirazin karboxamid vegyület Download PDF

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Publication number
HUE033177T2
HUE033177T2 HUE13738947A HUE13738947A HUE033177T2 HU E033177 T2 HUE033177 T2 HU E033177T2 HU E13738947 A HUE13738947 A HU E13738947A HU E13738947 A HUE13738947 A HU E13738947A HU E033177 T2 HUE033177 T2 HU E033177T2
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Hungary
Prior art keywords
amino
phenyl
pyrazine
carboxamide
methylpiperazin
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HUE13738947A
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English (en)
Inventor
Takahiro Matsuya
Yutaka Kondoh
Itsuro Shimada
Shigetoshi Kikuchi
Maiko Iida
Kenichi Onda
Hiroki Fukudome
Yukihiro Takemoto
Nobuaki Shindou
Hideki Sakagami
Hisao Hamaguchi
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Astellas Pharma Inc
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Application filed by Astellas Pharma Inc filed Critical Astellas Pharma Inc
Publication of HUE033177T2 publication Critical patent/HUE033177T2/hu

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    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
    • C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
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    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
    • C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
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    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
    • C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
    • C07D241/28—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—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
    • 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
    • C07D401/12—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 chain containing hetero atoms as chain links
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    • C07D401/00—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
    • C07D401/14—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 three or more hetero rings
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    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
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    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
    • C07D451/06—Oxygen atoms
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    • 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
    • C07D471/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems
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    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

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  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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Claims (5)

Szabadalmi igánypnOíöli
1. Egy (1) általános képiét szerinti vegyölet vagy annak sója:
(ahol R* jelentése 1-6 m&amp;mmtö$ a.lkíicsoportta! helyettesített piporazmüesoport í -6 szénaíotnos aikiicsoporttal hslyéítesítéít piperidtnifeoport, ν®φ· piperazinílgsöpörttal helyetteshetl piperidimlcsoport, amely Ivhjsáénatöbsöá alMleseperttaí helyeiteSíiétt lehel 87 A györíi jelentése benzol, amely egy vagy több szubszUíuenssel helyettesített lehet sz alábbiak köréből választva: halogénatom, '· »6 szétlátdmos alkifesopöít, an: elv egy vagy több balogénatöiftmal: és ~®*φ»φ szénatpntöá albíi)--csöpoí1íal helyettesített lábéi, ρΰρκοΙ ániely Ob isaésiáíppitös alkilesbpofttaJ belyetiesiistt lehet, imklazoi, amely i~6 szénatomos a ikíle&amp;o porttal belyetteskeít: léhét, vagy pirhrskHn, amely 16 szénatoméi aíkilcsoporttal helyettesített lehet. l.! jelentése NH-csoport, . . .',y R" jelentése bidrogébátép:vagy 1 -6 szénatomos ai ki lesöpört, \J jelentése vagy egy kötés, Y jelentésé X gyűrő, X gyűró jelentése .«waisí' bent aromás haíerociklus, cikloalkán vagy benzol, amely egy vagy több szuhsztituensssl helyettesített lehet az alábbiak köréből választva; halogénatom, -CICI ~6 szénatomos alkil}-, -Cbk dkloaikík arihesoport, aromás heterociklusos csoport, nem aromás heteroesklusös osoport, amely I -ő szénaíomos alkllesoporitai helyettesített lehet, oxocsoport, és 1~6 s^nafepps áíkllesoppíí, amely egy vagy több hafegénafemnml helyot^iétt lehet, L3 jelentése -NH-, -N(1~6 ssénatomos alkühesopori vagy egy kötés, M jelentése -0(0), Rá jelentése: hltít ögéiMtomi)
2. Az L ipnygönt szmstiAfegpJet pgy annak sp|ar aM L2 jelentése -0-, az X gyűrű jelentése bénzelpamsly í-6 szénatoroos atkítcsopofital helyettesített lehel és 1 3 jelentése -N! l-esopoit,
3. Az: ;t, igénypont szerinti vegyítiét: vagy annak s|ja> alQl:!!/ jéléni&amp;ífc 4K az X &amp;dirü jelentése egy nem aromás heterocikíus és Le jelentése egy kötés,
4. Az t , igénypont szerinti vegyidet vágj·' annak sója, ahol tÜ jpientgse egy kötés, az X gyűrű jelentése egy -néni· aromás ttsféröéikius, ás l/jeíerzése egv kötés. 5. A 3. igénypont szerinti vegyidet vagy annak sója, ahol az X gyűrű jelentése puroM'm vagy píperídin. 6. A 4. igénypont szerinti vegyidéi vágy annak sója. ahol az X gyűrű jelentése píperídin vagy tetrahidropiridin, f . Az L Igénypont szerinti vegyiiet vagy anöak sója, amely 5“[ 3-( akrUi0Ítomo).^ö0xiJ'éífttt:l-3« {{4-(4«ntetijpipep§gitt«1 *íl)fcaíÍjai^j»#}f|rMin»2-tkat!höxan*tá«. karboxamkk karboxarníd, 5-{ 1 »akfiloilpípori|ln-4síl)-ű-etíi”3-{; 3-«teíti-4-^"í4-t3ö^iípípss^t2tíía“ 1 -ií)p£perl^ií5^1 ^ i 1 j le ni tlatnino}plraZnt#2-karbakaín S't3'{akrilotlamíno)ténoxO'3A[4H4-a)etilpipemzíftA''il)föníljani!no}pírazm''2Aarboaamíd, 5d'34akriIoilamíno)fernTxíjA>'ebb3*{[4nnetoxb3A4~f«eti!píperazinA-'íl}feaülajní?io}píraziíi'2- karhoxamid, ;5ΗΙΡ^Η^^^Ι»οΜ^»-3^{1οχί|4<®ίί{»3*(|#^|^1ίΜ#βΐρίρΡΐ«Ζΐη*3'*Ι^ρ^ίη»·ί#· i ijfenil} amino)pirazin-2-karboxamid, 5-í3<akriIoiiamínö}fenöXi|A>azopropiI~:X{[1 A^'^atílpperidm-4ót)AH-pirazol--4-:íÍ}amino} píjazin-2-karhoxmnídv 5d;3Aakr!Íoilaminia)teaoxi]~3A{44í3s)^r4'^íiBetíipíí>orm'inA'Slll%nii}annno>'6a4iípírazin'-2~ karboxamid, 5~[3Aakrí}oiiamíno)fenoxi|%5<{44(3R)":k4atimetiipiperazíjrvidí]feníi}amíno)-'6-eti!pÍ!-a2Ín-2'· karboxamid, 5 < í --á kr í íöi í piiS©rit31:tt>-4 - í «í i < 14 - [4 t í Íj5 í jpss ra^syí ^ 3 ·>i i )ρ1ρΐ?ϊΊ d í ít - í ^ i 1 j fb iá í í) a I ít o>piraz:Ítx^ 24;arhoxatnid, 5~i j {3R)~ 1 -skyilöüpírrohdm-d'ií jox s | o-et íi-3- {[4d4~m«íilpiperazin 1 di)tpíiíljapnno}pjrazíífe2^ karboxamid.
5- Í f (3R)“ 1 ~akrílQÍipíptnidin-3'-UÍ0X t} -b-eÓl-3 -{{4-.[4-{4-meíí{p!perá?in-l Aljpípéndin-d -U jfertil} aroinojpi razí n~2-karbox&amp;roid, 5-{{{3Rjt-1 <N-[4~(4-metj{pipentsÉI?]-íi)pjperidlö^|[ * vaggf· 5^|5^í;alcoÍ^íls^li>o)-S-OuorföaQ^i}^6>-etil^3-||4~f4-^^tií^íper£i^ <4l)ife:ítíl!sííiíí>:0}p:irs55S35>^~ karboxatnid* vagy annak egy sója. ík A ?. igénypont szerimi vegyületet vagy annak sóját és egy gyógyászatiiageiiogadható segédanyagot; tartalmazó gyógyászati készítmény. 9 A 7, ipayposn szerinti vegyölót vagy annak sója alkalmazása EOFR T790M mutáeiórá pozitív rák megelőzésére és/vagy kezelésére szolgáló gyógyászati készítmény előállítására. 1Ö. A 7. Sója F.GFR Í79ÖM mutációra pozitív rák kezelésiben való alkalmazásra, 11. A ?. igény pönt szerinti vegyit let vagy annak sójay amely #rp^(aló-lloilammo)íenost]'-óvjxoproptl''3'· {[Ί^4-m«||R|pj-azin'l>U)fenilJamino}pirazin"2«ka^^il#vagy annak sója. 12. A ?. .I^íí^giííí;.annak sója, amely 5··( 1 -akrik>i!píperídin-4-il)-ö-etÜ-3 -((3- metíM-(4^4-meti!pípera2Ín-l -íl)piperitöfoiM]^ annak sofa. 13. A 7, ágenypóru szerinti vegyülni vagy annak sója, amely S-flDR}G-akríloilpns-ólidím3Al|oxij'6’' eilGAj4"I4^ióatílpiperazinAÓi)piperidíiiA4i]ieínijamínőjpka2ÍnG~fcarbexamiCi vaigy adnak sóiá.
HUE13738947A 2012-01-17 2013-01-15 Pirazin karboxamid vegyület HUE033177T2 (hu)

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EP (1) EP2805940B1 (hu)
JP (1) JP5532366B2 (hu)
KR (1) KR101985050B1 (hu)
CN (1) CN104080774B (hu)
AR (1) AR089727A1 (hu)
AU (1) AU2013210438B2 (hu)
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HK (1) HK1203491A1 (hu)
HR (1) HRP20170226T1 (hu)
HU (1) HUE033177T2 (hu)
IL (1) IL233437A (hu)
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PH (1) PH12014501456A1 (hu)
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RS (1) RS55704B1 (hu)
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