HUE031638T2 - 2,6-diamino-pirimidin-5-il-karboxamidok, mint SYK vagy JAK kináz inhibitorok - Google Patents
2,6-diamino-pirimidin-5-il-karboxamidok, mint SYK vagy JAK kináz inhibitorok Download PDFInfo
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- HUE031638T2 HUE031638T2 HUE09755219A HUE09755219A HUE031638T2 HU E031638 T2 HUE031638 T2 HU E031638T2 HU E09755219 A HUE09755219 A HU E09755219A HU E09755219 A HUE09755219 A HU E09755219A HU E031638 T2 HUE031638 T2 HU E031638T2
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- 125000005296 thioaryloxy group Chemical group 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000002446 thrombocytic effect Effects 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 238000001685 time-resolved fluorescence spectroscopy Methods 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- UJLAWZDWDVHWOW-YPMHNXCESA-N tofacitinib Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 UJLAWZDWDVHWOW-YPMHNXCESA-N 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000002750 tryptase inhibitor Substances 0.000 description 1
- 208000025883 type III hypersensitivity disease Diseases 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000003156 vasculitic effect Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 108010047303 von Willebrand Factor Proteins 0.000 description 1
- 102100036537 von Willebrand factor Human genes 0.000 description 1
- 229960001134 von willebrand factor Drugs 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000012130 whole-cell lysate Substances 0.000 description 1
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Classifications
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- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
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- 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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- 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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- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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Claims (5)
- ásé-oiA^siNó^mi^iöiH-s-iL^RBoxA^!P0K, üiNT syk ¥αθυ jaκ kînâi INHIBITOROK Igénypontok1, Az í„ képleté vegyuietU) vagy utóbbi győgyszerészetiteg elfogadható sója, ahol a Ö1 cfo,* őiklö&fkil cpclenâlisan 1 következőkből álló csoportból egymástól függetlenül kiválasztott 1-4 sztfosziltuenssei xzubsztituálva' CA$ álkik am;no hidroxii, Üfos alkfokarboniy am Ino-Aarbon II, Ci-v'alkoxi'Aamoolkaobno, an|Afo.raíkoxM<arbonik amino, fenil és heterocikill .Ci^sikjlén; Az A' a kővetkezőket tartalmazó csoportba! korul kiválasztásra; H, Cfo§ alkii, amlno,. amlno-'karbooll, bldroxü, C;.* aikoxt, Cm bafoaikli, Cfo* alkenil, Cm a! kinti, oxo. manó, C ; s aikoxhkarfcomi, C3.3 clkioalkll, aril és heterooiklü; és minden egyes heterocikill opcfonállsaoszubsztttuálí a kővetkező csoportból kiválasztott 1~4 szubsztltuenssel: Cm alkit, hala. oxo, amlno, Ci^alkoxi. Ci.aikii'-karbork!, aryi-C·^ aikoxl-Karbonü, amlno-karbonlf, ankCmmlRHen-karbonll és C-m al kik szu Iron 11 Az Y- a kővetkezőket tartalmazó csoportból kerül kiválasztásra. (a) aril; opcionálisan A3 szobsztlfoensssl szrfosziíiuálva, Rfo egymástól függetlenül az a kővetkező csoportból kiválasztva: Cmalbii, Crszlkoxi-C mailéi, amlnofoatbonlk hidroxii, oxo, halogén, hldroxl, Cforaikoxl és Cm alklkszulfon!!.; (b) neteroar·!; opcionálisan 1~3 szubszbfoenssei szubsziiiuáívs, FCh egymástól függetlenül az a következő csoportból kiválasztva. Cmstkü, CmaikoxhCmalkf, andno-Áarbonil··, hidroxii, oxo. balogén, hldroxi, Cm--a!kcxl és Cm alklkazuiíonl!.; •x A M il3 lietaroolklil vágy hateroatit legaiibfe egy ^3 csoporttal szuttótualvá, amely s következő asoportöől került kiválasztásra: ammo Si-& álkík <5ι.«Λ«0» C'i^amít-Ks^onHri ^«oHíraalkfi-karbáníl, tiptaroeiklil-YorOonih jpí.-s^KINksübsníl^minö, 03.sdW^ii4tefeonlf-im'lno: hetemciklil-karboalkam^^ ^i35 mkil~pzuauaií:S v*#* clklpsiklM^lfcnil és hetarociklllmzuiföni!; és ahol az 1¾2 tW0bá opcionálisan mipsztitpM ®0: m9Y n amelyek egymástól föggatlenoi a következő kemte* kíVsd^eaáma. £«* aíkl, Ci-seikod háiő; amiPeYaroonlk axa, Ndtöxll ^lno-0^^^®n» V'-i4^koxi~Mi4· aiklléh, CnsaildkkarhQhll C^«ÂlôâM*-kârb0rt)i».: haterocioii^kar:hôîéî; ivitMúé* karbanlkamino, O^Moil^l^imöfíihamlno, hitaroomkl'marbosííkamsna:, tor aíhiksoMifenii OM^m\mrnmm alklgalkllén, pgterosdl;; ahol a siktaaikií mono* vagy gelieiklusos: szénhidrogén %Ml· ®lmml vagy alkiml csoportot latent, amply áthidalt gyűrűt vagy splroigyőrűt κβροζηορ és amely agy vagy tébb kettős vagy hármas kötéssel rendelkezőm. I, M 1.. igénypont szerinti vagyölei ahol a -Y'-R3 rnoiekularész a következő ösopörtbői kerül leválasztásra.as Ya N; CH vagy C; A&R^a következőkei; tartalmazd csoportból kerül kiválasztásra: H és CAssIkil: mindegyik R*'· egymástól függetlenül a következőket tartalmazó csoportból karül kiválasztásra: Cumaiklk aminoAarbenih Ndroxií, oxo, Cv§.aikdxi és haló: mindegyik R*5 egymástól függetlenül a következőket tartalmazó csoportból kerül kiválasztásra C<.*· alkil és heiemcskili: a p alsó Index 0, 1. 2 vagy 3: és a hullámos vonat a molekula több; részéhez való csatlakozási pontot mutatia> 2» Az 2, igénypont szerinti vegyuteü amelynek a képlete lel :vagy gyógyszerószeílieg elfogadható tautomeric. sója vagy sztemolzörtmne.,
- 4, Az 1-3. igénypontok bármelyike szerinti vegyület: ahol A D1 oikloproplL
- 5, Az 1 '3. Igénypontok bármelyike szerinti vágyóiéi aboi A Dl olklobutii S, Az 1-3 igénypontok bármelyike szentéi vagyaiéi, ahoi A D'! cAlopenilL ?.. Az 1--3. igénypontok bármelyiké szerint- vegyidet aboi A D: clklbhexii.3. Az 1. igénypont szerinti végzőiéi, amelynek a képlete:vágyvágy dyOgyszaroszslliog eliogsdliaiő taatomege, sója vagy sziereolzomene.. Sí Az 1. Igénypont szerinti vegyidéi, a következőkből álló csoportból kiválasztva: 24 4-(4-ecet|i-plperazin-1-|l)Áenlkaminö}-4--{ clklobirtikarrùnoy pinrrkoin-S-karfcoxâmid: 2,(4~(4..@cetli-plperazinAnl)-3-kiönfbhli-4nllnö-4-{clkloprüpikamlno)-pirlmidln-S- kerboxamlo; 4'kcikiópropAantino}~2'(4-(4':propionii-plperazin--iéi}4enikarnino)-pidn'kdln''5'' karboxamio; 2-(4-(44clklopropán4 plpetazitvl-il) fenikaniíno}'44cíklo^ plrkttldin-5- karboxamid: 2~(444·^acβtii·'Z'OXö“piperaztn'·1'4l}fsnlkarτïino)-44olklöpropil·smlnö)ρinmidln-5- karócxamib: 2^4-(4-acetä bpi pe mxi m 1 4 ï)~3 - f lu or-fe rd-am; no-4·· {clkiopropil-amsnorpirimkii mb-karboxamid; 24 44 4~acetsb 2-ötr'barnoii pipamáiml 4p fenika^lnoJ-aPciklopropibamino} pibmidim karboxamid: (R42-44^4--3cati!'2-meäkpiperaakp14i}fsnsbamino)'4--{csk!öpröpi--aminö}'pirimidin'J·· kardosa mid; {Κ)4<(4>>(4~Βδ@0^2»^©ίΙ^ρΐρβΓ8ζίη~1“Ιί)^ηΐί-«ΡΡΐ?ηό'ί~4«·.{0(Κ!0ρΓορΗ“άηίΐίπο>ρ»1ριΜΪ.Π*§“ karbosamid; 246'#··acatíl·p5peradΐr^χ^aΠ-ρiPdiπ4'4Pamkîo}'4-4ciktoprόpl''aaPπü}'·píπmsdiπ--b'' karpoxamid; «{niati.bs2u!fedH}pfp8rtclin»4-lf}-%nH-amipphp}fimidiP~S'· karboxamid; 4- (clklopropikamino}”^”|4“f4^m@tik§2.uiföPi!}.pipp'rä2ln-i4f}4p'nif“adiiPö)''Pifimidin<-S*·' karboxarnid: 4'áGÍkiopropíl-aminö}->2H4--(4daPPsauiíonil}ptepraain4-4Pfeni!'aniíao}'pirimidlrv5- karboxamid; 4~(eikióbutk-'aniíno2-2H4444rnsdi4buifön|Í9piparazin-'1 ai)4anibaminoppinn';idin--§-karboxamid; 2--(4-( 1''aGebi''pipendin4'd)''fenikanPrm)-'4-(cikioprQpii«amino)"pino4din'5~kai'boxamid; {ciklopropikamsnop2-'{4-( 44pirroiidir>-1'4arbo?^i0pipendim1-4}mniPam]rmrp;rmiidin>5-karboxamid; 4''(cikiqprop!i«aniino)-2H4444modoiln-4-4arböoi!)piperidinmai)fen;kärnind}~pirimidiro 5- karboxamid; 4'-(öikiopfO0H'äm^ö}><2“(4-(4-{pikiopropi1~S2Liiforfä!)oiperaz!rf-1->if>*fen1l-ämiHO}"pinm!din~ S-karboxamid; 24444-'acePbi4-4iaxopéa4ai}'fpaiiama^o}-44Gik!opropi!»am!no)-pÍ!nmiaín-5- karboxamid; 2-'(444~acetamido-p:pendiro14i}4enli-4rriino5'4''i4ikiopropi;-amiao}'^inmidin^ karboxamsd; 44c;kiopropii'4mino}~2-i4-diox0'-i;omioffoiino-ferimmin0;i-4inp4din"5''karboxpm|d! 44cikiopropli'-am!no}''24444''(2-'rnptdXi4tii)pippraxin'44i)--faoii'aminopplnmidsrx-5·· karboxamid: 44cikiopropiimniino5''2'-(4'44'4k|'-nietii--acotamido)-piporidin'14l) foaiPamino} pirimidin-S'karboxamid; ès 2'44<44-(arniao-'meüb'mipoddin4'd)foni!'-smind)4'(cikiop-'Qpii'mo4no}--pinrnidin''d>' karboxamid. IQ. Bármely eidzo igénypont szennt; vegyQlst amben V39V a^atä testoen sebészei:!: vagy ísrápms oèfra velő toihaszoàiàara 11:, Qtpr? amely az 1-i. igénypontok b^rî1®^^ seermti vegypietettartalmazza, efegádbaió:hpmozévai vagy hígj-vai κορ,&ΙηΙιρ,
- 12, Az l-δ. igénypontok bán-neiyike szennti vegyié-· a következő oePpôPéôrklvàlsoÂf betegség; vágy alapot kezelésekor történő •afkäiQ^itra;: karoiovaszkytiris betegség, p-iilaoieós betepég, autoimmun betegségé® seépr^f®ratív iMéifenasség,
- 13, Ár tM igénypontok bármelyiké szerinti m0&r$msí^m:k%m\mm, 0 következő csoportból kiválasztott AarpsoeasEküiáns betegség: részíenózis, trombózis, immun trornboeiiópéniás purpura, eepâne áltat indokait tromboPitopinia, dilstáit kardiomiopátsa, sarlósejtes betegség. etereszkíarőzia. miokardiáiis infarktus. yMzkuíáris gyuiiadás, instabil angina és akut koronába szindrómák; á MvblkezP csoportból kMíasztöt gyuiiaoésoo feetegsig: áliergla. asztma, reumás artrlfisz. S sett által médiáit betegségem $M- Például noopoőgkin iimfbme, ante éöszfoKpiö szindróma, laposz, pszonpzis, szkíerozls muítlpteX: végstádiurny vesebetegség is Croho-beiegség; a következe ssopoóbÓirkiváiapztoP autoimmun betegség; herneiitíkus anémia, immun tromPocitopéntás purpura, szklerözis rrmröptek. pszoriázis és SibommszindrŐma, vagy a következő csoportból kiváiasztott eejtproileratty reoéefienesség:: leukémia, limtóma, mieloprollferativ rendeilsnességek. rosszindulatú hematológiai elváltozások és kfőnlky§tprípéQi'stmie)pffbrózíá> 14, A 11 igénypont; azenotr készítményt, csomagolást és a használati utasítást tartalmazó kit:: i s, m 1 igényppnf »«véltek m^mk « szerkezete:;vagy utóbb: gybgys2srè§zetiteg elfogadható $őla.
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US8338439B2 (en) | 2008-06-27 | 2012-12-25 | Celgene Avilomics Research, Inc. | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
KR20130099040A (ko) | 2010-08-10 | 2013-09-05 | 셀진 아빌로믹스 리서치, 인코포레이티드 | Btk 억제제의 베실레이트 염 |
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CY1118559T1 (el) | 2017-07-12 |
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BRPI0910560B1 (pt) | 2023-01-24 |
AU2009251863A1 (en) | 2009-12-03 |
PL2321283T3 (pl) | 2017-01-31 |
ES2597441T3 (es) | 2017-01-18 |
AU2009251863A2 (en) | 2011-06-09 |
NI201000176A (es) | 2011-08-08 |
LT2321283T (lt) | 2016-12-12 |
PT2321283T (pt) | 2016-10-19 |
HK1158179A1 (zh) | 2012-07-13 |
IL251655B (en) | 2020-05-31 |
NZ589314A (en) | 2012-10-26 |
IL251655A0 (en) | 2017-06-29 |
GT201000298A (es) | 2014-05-07 |
MX353206B (es) | 2018-01-08 |
IL208637A (en) | 2017-04-30 |
IL208637A0 (en) | 2010-12-30 |
ZA201007045B (en) | 2012-08-29 |
CO6331433A2 (es) | 2011-10-20 |
AU2009251863B2 (en) | 2014-09-25 |
DK2321283T3 (en) | 2016-10-31 |
BRPI0910560A2 (pt) | 2021-04-27 |
SI2321283T1 (sl) | 2017-01-31 |
MX2010011464A (es) | 2014-06-16 |
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