HUE031917T2 - Pirimidooxazocin származékok, mint mTOR-inhibitorok - Google Patents

Pirimidooxazocin származékok, mint mTOR-inhibitorok Download PDF

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Publication number
HUE031917T2
HUE031917T2 HUE13712331A HUE13712331A HUE031917T2 HU E031917 T2 HUE031917 T2 HU E031917T2 HU E13712331 A HUE13712331 A HU E13712331A HU E13712331 A HUE13712331 A HU E13712331A HU E031917 T2 HUE031917 T2 HU E031917T2
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oxa
group
mmol
compound
dimethyl
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HUE13712331A
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Alain Braun
Olivier Crespin
Yann Foricher
Gilbert Marciniak
Nicolas Muzet
Eric Nicolai
Cecile Pascal
Bertrand Vivet
Fabrice Viviani
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Sanofi Sa
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    • C07D498/04—Ortho-condensed systems
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    • A—HUMAN NECESSITIES
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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
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    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings

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  • Health & Medical Sciences (AREA)
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Claims (5)

  1. Iasi|3sd8ílí»8 %Ow|Ks?rts>k . S:. -ÍSS !..;..v::íkk.. :, ίν·:ν.^. .c.diï'.bS...!,S * ,.-ν,-νϊχΛ'χΙί-ίί'*
    ahoi: nosKäogvik R; csoport jdoort.-a- oavo-ssvO %'ii.<kS; ;nh (kY-CsVJkii, 'ook-.Ortvc, hogv kàî R; csoport. cosc-y ο oíortoko gÿürtâ κόΐ Oik'OOOő 0Cv0ák>npipí hviycy^ocok ah Ösa.iv·-'<-4--":·· Jódba- a tnorNin gyűrő vd, miáíJaí bivikkaos hokoodUusos srortíosdcí Okos. ~ Rf.é&amp; Rs jelohRs-o ogymásMól ÛJggoüvaâk ' 0, vagy. ·· (CrC;;J ïdkh < áÖ|R% ^P^jplgyiëssî - hí. - RO'-kYRölkoxi Cäosson, - -Irf -Rtó csoport, afeoî: • L. jekmése (€rQYdki!éo csoport - R,,·. jelentése &amp; követet 'OR;5' ** 5' '®&amp;v * ‘àïomos heâSrtRîkiuspalpsSÿ âddhMdfRR "RiSí -k-OOR*-, -CO-Rso "'-·5^ο· ^gy -$&amp;.Σδ&amp;ρ csÍ!pprttóha^hts*h sudg sags - 5' \,sgy í>-öi:pfïïîïs íísstsrocϊΚϊΐ-íö, *:V?*> '^Rs ο *^Λν>«*" '-^! jjomai s-aRkoRfesh, - Gs jdemése kétértékű idtH vagy Oo-atmnos hekoosriï csoport* ;s<-i>!-: s-4 50 csoportsai sZubsKtstuóií egymástól- fágg«Uenő* &amp; kövvrtkcEóK k«x«l s-áiasrtva: haKJskat.tkim, ΌΚ,„ csoporté® -tCr'-oHM icaopoít: sísely kdoR #&amp;(&amp;$$ • X;: Oten-ése Ό- vagy -HE*;-1 - X? j«fe«!«se 8?>«s km% vagy -COSRfir. -CORH^-O- --:..4:50-, -CO- vag> -SO.. - csoport, - Rs jde-rtéss: - H, • Lj-R; csoport, ahok t ·> s'>U ',s s t dk >, '\ U V * ' ,« ii*«00íc R p k }ÍCs \ >S 'tV. íO\ s s o *OV > -a ·' OX;.;.:, ikhÄgöÄsk 5¾. -i Oa.kOkiU.vg őri N jKïfïvvjl kw a*nO ö ton .vV\^g' Ob t vb wv'i- ' sr "vm;uu. a? On* * ! ^.^Ok Hiàlvâlsg^Â|.v.îî#v:· -G-Xj-Cj-s < SigKiî'h &amp;h>>r >; - RRaUxe %yvassvv URO v&amp;gy ~Oh --CO vagy '>· H :·· csoport, .V N * t *Ν*Λ ^ v'V N t> »tf» K'k ,ik. Ο ,χΛ «»'*' ' K ^ ""· x W'' v " äöbb R»;; csop-.xtN y?.nbvUï«iUk o:?s Jsfe» A^msms gyÄ öäidy adó* esette« effigy 0t*> R*; Opp mÉs^^ôi^ vagv -Gr->OG> együ« '?· lO-aton»* komfewiK b»< ÈMtM#&amp;oto<xîk k -, x ^ Ο, .μ. ΌΓ v'o-î *>'1 ftK\vîni'l5 -5 vx*ctU wk b > V ->'* «;|kÎ|pgOSiil5ïi ' COOä'O, -CO*H>», -OR'i. -NR-^R·^ -COKRUR·*. ON vagy 'S{()).-R-j cssapork , (ΓΧΥΗ&amp;ϋ csoport. amely udou «*e»te« egy vagi R>bb R..v csoporttól saahaxtiiuält í>N'ágy sRopeOÉ#R®iy vagy Obh oxigéaftiommal megszakító«. „ {CVC*)-aíko?d csoport, amely adott esaten egy vagy ÄÄ" eay vagy iöbh «Sigénakxïüxal megszidott, • a énéke 0, i vagy Ik • m értéke 0 vigg SU - p értéke R. 1 vagy 2, . R„, R* K&amp;éu, ^ KSl! S.'b K>j, ** R^ R- *«- R«:' Ríí< W R*!> R'"' Rí5> Rí;, jR · s, R·?^ R-V R*s ex R- jekvtese egymástól RJggctieoél 5 * v»gy (C5· C«)-aMcR csop^k ·«>·'*** **'** M R,, v,svtaK ^ ^ ' ^,ssK'-'K"'' tv·' ^ > jeleotese -ORoî vagy -NROO csojum. rn i,R, '.ο.*, ' ^ , R:,sy, F,,. Kimévé egymástól föggvteol halogén^OsIN^ncnopon OO! bázis vagy savaddk'Os vo íoraiajaban.
  2. 2. Λϊ|. igénypont sasÂC^?^^« V0^iRü 's kövUkivék kb#Rvalasstvsk:
    (R| akoi *u Rv. Rs<, Oj, X;. X.; és az í »g«»y^0>a>» megtiâtaroaou. havi' vagy savaddiviôs só forfitójag*«,. 3, A:? I. vagy 2. äg^sypöäA vegyük*.. sAél :lisÍ«fesíi:#»e; - H, - (CrC:A-ülkn csoport 'iVïsi?»'S.«^^s^íiísiiál.í:i -: 1,:8½ gsogOrk ahol: • I ; jvkolÁw íAA-Ca)-í:?ki;*e ésepöít,. -> .ks§J§lőoíáw4--feöve^^^:fetóí,-'vá|ss?io«x'S8pő«:->CÖÖ8.'kí 411¾¾ '$* vagy Sostööoss isstereaikley amdy· iidoSlesoibea -:C450Ry vagy -CO-· RSä esopems s sssRssetRuslg vegy * S- vagy ?>>-a!osses fss?eroeikks, osaslv sAblt esÂea.*1%j osoposllal saolAatkaàlk - R! !t Iis.;, H :.::, E ss, ll!?t R;v 8; R:-: uíkütüs« az !.. i'a^glíStáítíassRi 4, :Ae y$. igáftypomok bámklyike yeerísa? vegyük?,okol 0( jaleatáse köíáAéka fám! vssgy gidRÉ esö·-eork amvsy aboli: ase!bvsi Sy <Aíg5öRla! ?A5Áse!Áeá!g amely esopon hak>gámalmsmk Rézül válsszioR, $. Re A4. Igényimsiíok Msenalylke széria!:! vegydíet, almi Aj jelenláse -NR.sÿ, esepark aboi Ry, JabssMse ae L :i|RaypAÄ&amp;5i ísegRsláí'eeöt!: A. Ae US, Igésyimsiiok Msenslyske szériák! vegyük?;, -sírni Ayjalenláiíe viáóMRjy? vagy 4188-, ?.. Ae !-4>. îgàvypsyyaà hámisüylke seerisRg alábbi (ül) kkgletll vagySk!;:
    ábol: - R; Rkmésv ÿCyCgyalkU OAsport * R'.< és R4 jvlensésv 41 vágy -F, absit agy kali érivsii. bögy bá lik sk R?g ésögmí egyikéMk jelybiésy -F. akkor a íblaíkkák 4 jvkssiésv 4!, • .X-: jdcmkHa -(4444 :.,- vágy 4448--, - ,¾ jáköíéSe: - - ! .··.;- ÍV: csapon, alak - jaiankHe ηΑ4Α;-;4κΗ8': vagy <<YC8-<;k!o;4!.:iím csoport - R- jAviXésc a kbveskeeő yspgiAtMI islásylÁít: · H, vagy - ORsy - -4b-4.:-CA esoger?, elsői: - 4.5 jgléakao egyseáiW köles vagy -O- CaoseH, v^gyéróíkö 6 numix gyök, |fe1^^fey.'4^«ft>mn<s. gyÓí^iiMS^afei'^fe«« «10' VW ^«!> ¥*&amp; - fi B.s< RjiV K*,jeteft8ése sa L IgSavpomfeim bà?K vagy savadásdó- só fonsâiâbsîs.
  3. 8. Az U7. í&amp;nypM<ik bárm^s <í*r!n« vegyafcs. ahol R, isim*«« χα·Λ&amp;*ο$οη vsgy eaksossört. ó. A ?. vagy H, démont «Äv^ni«. amsíy a kûY&amp;k^ hm* vtímmil: ......,.»j;.,^^«;i».^^-.^'N^*·'··.·.·.·.·.·.·.·.·.·.·.·········;*.**··ν·*·:*·'···········ν·················................., ,·, y
    .- :
    «î^so' m'vV* «νί·ν··.'ν·· ν ··· -'V.: (\.7 .'.vv«;.vvv.ív,
    foglalja an alábbi U·; ΙφέΉ: S«1 V^%:<SSÔ|>Ï5É' laôc j-¾ à:iï ί^ϊΐί^ί^^Lis;Í!: ^ié^feíís ôÎeÎ:S5SS::
    ahoi Η.·, n. in. R·;. R„ R<, i vs X. n îinfcsï ;«: 1 ikiiyponibsii Rn’gha· anyait, •AI mMI vfcgÿüM jfi» lèuïf. f I, Epmsina b b. igenvponsk harsaik**· yakkkÔI shn! X: jelenik* -v^ *s \ iS.tu , OMiu -, î' > X >'s* n< <'x>l*li' *' ΉΑ 5;) a (KXXVi ksptkbvegyykaS«:f.xíkl-reakcséja:
    jhot η. Ri, m, R-, R« «s mçgtutfàro«»* és l. 6> ^'k'més«.#îfestâ.»{»i% R4F,.:N-<C>H;r NR^-Ci!4ij;.y! képlïV vegvtlleô«· sfoX V, R,·,, R«<H FV sekmest· a,> 1, Îgà>ypûosb&amp;!> meghsV a>Ai::. és Fi „,, sdsnî&amp;K: k-xc-m-äv vagy-sixmtgyíV. : miàïtSi az (I) kigkîû vegyüks jd» MV*siisl X. selsDV« -MR*;· ás K? jdemexe -CONS^-v
  4. 12, Bprâx sa BR, iaenypôîsiok bàntîefvto saerksü {1} VpVû vcgyskt efoáRitásáta, ttaseiy kinalm»«« az. sîébkl: q) lépést; >:|| az aïM>\ (Cï) kèpktu vegyöki V! vçgsVt mikkel támadás:
    vs*v a <:-\ X ,jt'!,'!'; V \s s ' ',^à( '- îvos vîs ^o^a'-vowsî, cgy ii|t||yI) Xlikk vegyükíem
    Vf * s \ t x \ î-n Ou>!k > ^ 'ί1!'"·1 fi >1--' ' ïrùàRs: 3C «r> kqW vágyók; ;tm k-tm, *;X.,%ègys^::iï;g»;sijdle6ï^^^ s Äk$R BiyilV iskyaiy mmk%mgy&amp;lé^k M, Oyágyássaé! V:V;mág·', :|êâlemeKV^;hegy «s. sVislmsasa as S -X. sVnyps>ms>Sç R&amp;Älyi V sâ«-fssïîi vegykkssk vsa y ;î;hV; övágy;X?ö!sag t’H&amp;gsdUató sóját, es VWb agy ey^gyasístusg «sitog»dtiäa> v-> kkémvagas, j.Si M M>, igófiYp^rskik bSrtaefesis ibssv mgy--m«|.é1êtlÂesÂé86· sikátor v
  5. 16, Λ S 5. Îgènypoa; %zmt\li vegyi!V V. g>VVisses ás imstsm5bemgségck. mskmbete&amp;seg. cihssss, s vagy $s»ra>?it&amp; VVtafeeteg..ogek kseü<Heh<m vagy snb§ek>m«í>«B K*HUKt 'S^m«*-*··»«.
HUE13712331A 2012-01-26 2013-01-25 Pirimidooxazocin származékok, mint mTOR-inhibitorok HUE031917T2 (hu)

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Application Number Priority Date Filing Date Title
FR1250768A FR2986232B1 (fr) 2012-01-26 2012-01-26 Derives heterocycliques bicycliques, leur preparation et leur application en therapeutique

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EP (1) EP2807172B1 (hu)
JP (1) JP6068508B2 (hu)
KR (1) KR20140125389A (hu)
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AR (1) AR089782A1 (hu)
AU (1) AU2013213261B2 (hu)
BR (1) BR112014018226A8 (hu)
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HU (1) HUE031917T2 (hu)
IL (1) IL233774A (hu)
LT (1) LT2807172T (hu)
MX (1) MX348841B (hu)
PL (1) PL2807172T3 (hu)
PT (1) PT2807172T (hu)
RU (1) RU2627269C2 (hu)
SG (1) SG11201404325VA (hu)
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SG11201602446VA (en) 2013-10-16 2016-05-30 Shanghai Yingli Pharm Co Ltd Fused heterocyclic compound, preparation method therefor, pharmaceutical composition, and uses thereof
CN107001317B (zh) * 2014-09-29 2019-05-24 山东轩竹医药科技有限公司 高选择性取代嘧啶类pi3k抑制剂
US10307707B2 (en) * 2017-05-17 2019-06-04 Thomas P. Daly 1-amino-2-methyl-2-propanol derivatives
EP3849535A4 (en) 2018-09-10 2022-06-29 Mirati Therapeutics, Inc. Combination therapies

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ATE427310T1 (de) * 2002-01-18 2009-04-15 Kyorin Seiyaku Kk Kondensierte bicyclische pyrimidinderivate
EP1562956A4 (en) * 2002-11-22 2007-10-10 Japan Tobacco Inc HETEROCYCLES CONTAINING FUSED BICYCLIC NITROGEN
CN102264732A (zh) * 2008-11-11 2011-11-30 艾科睿控股公司 PI3K/mTOR激酶抑制剂
CA2763008A1 (en) * 2009-05-26 2010-12-02 Exelixis, Inc. Benzoxazepines as inhibitors of pi3k/mtor and methods of their use and manufacture
US8912178B2 (en) * 2010-05-19 2014-12-16 Xcovery Holdings Company, LLC mTOR selective kinase inhibitors

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EP2807172B1 (en) 2016-11-30
UY34594A (es) 2013-09-02
RU2014134640A (ru) 2016-03-27
BR112014018226A8 (pt) 2017-07-11
AR089782A1 (es) 2014-09-17
EP2807172A1 (en) 2014-12-03
MX2014009084A (es) 2015-02-05
CA2862747A1 (en) 2013-08-01
US20140378433A1 (en) 2014-12-25
LT2807172T (lt) 2017-03-27
DK2807172T3 (en) 2017-03-06
PT2807172T (pt) 2017-03-06
CN104203958B (zh) 2017-05-31
ES2617880T3 (es) 2017-06-20
US9120812B2 (en) 2015-09-01
FR2986232B1 (fr) 2014-02-14
HRP20170288T1 (hr) 2017-04-21
TW201333016A (zh) 2013-08-16
AU2013213261B2 (en) 2017-07-20
KR20140125389A (ko) 2014-10-28
AU2013213261A1 (en) 2014-08-21
PL2807172T3 (pl) 2017-05-31
SG11201404325VA (en) 2014-08-28
SI2807172T1 (sl) 2017-03-31
BR112014018226A2 (hu) 2017-06-20
WO2013111106A1 (en) 2013-08-01
JP2015504914A (ja) 2015-02-16
CN104203958A (zh) 2014-12-10
TWI572608B (zh) 2017-03-01
RU2627269C2 (ru) 2017-08-04
MX348841B (es) 2017-06-30
JP6068508B2 (ja) 2017-01-25
IL233774A (en) 2016-06-30
CY1118852T1 (el) 2018-01-10
FR2986232A1 (fr) 2013-08-02

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