HUE027770T2 - Triazolopiridinek mint foszfodiészteráz inhibitorok bõrbetegségek kezelésére - Google Patents
Triazolopiridinek mint foszfodiészteráz inhibitorok bõrbetegségek kezelésére Download PDFInfo
- Publication number
- HUE027770T2 HUE027770T2 HUE09795687A HUE09795687A HUE027770T2 HU E027770 T2 HUE027770 T2 HU E027770T2 HU E09795687 A HUE09795687 A HU E09795687A HU E09795687 A HUE09795687 A HU E09795687A HU E027770 T2 HUE027770 T2 HU E027770T2
- Authority
- HU
- Hungary
- Prior art keywords
- methoxy
- pyridin
- triazolo
- cyclopropyl
- cyano
- Prior art date
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- 238000011282 treatment Methods 0.000 title claims description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 23
- 201000010099 disease Diseases 0.000 title description 14
- 230000002500 effect on skin Effects 0.000 title description 12
- 239000002571 phosphodiesterase inhibitor Substances 0.000 title description 2
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- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D471/04—Ortho-condensed systems
-
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Claims (12)
- TEIálOLOeiIÖINEK MiNT FOSZFODíÉSZTIMM ÍNHIBITIROK BŐRBETEGSÉGEK KEZELÉSÉRE Smheétifa&i tgétippMitote % Vagynlei, ami?!}· a következő: 1 általános kepletü;I ahol Rí jelentőse Cj.í-alkoxk.miit amilyen a metoxí, raw*-, di·· vagy iriflum^neíOXi, halogér; vagy hidroxi: R2 jelentése. aikiL cikloaikil, alkibdkloalkü vagy cik{oalkil-(C(0>NR?Rsk amelyek közül mindegyik opcionálisan helyettesítve vart egy vagy több szubaztiíuensseí a kivetkezők közül választva; Rg % jelentése hidrogén:, halogén, áíil hetetöárik hídröXi, áiöl etkloalkxk betetöcIMoalkil alkosi, oxo, eiano,: «im amioe-alkih alki-amino vágy dialkik-amino; 'Ri jelentése hidrogén, balogén, hidroxi, oxo·,· ekno, karhoxi vagy trihalogémmetik vacv Ro jelentése NR5R*. -C(0)NRvR* , -CíÖjlE, -COORv,' ' -NRsCtOJNR^, POOJNIGR«. -0C(0)Ri, N'C{Ö)R?, -OR?, -NSO>R7. •SCöNRrR* vagy •SöribrRs- ai kik clkloaikil alkenil alkinií, aril heiernarik cikîoalkü-alkil. cikloafkü-alkend, elkloaikil-alkinil .dkioalkenil-alkti, eíkloáliemlmltei| clkloatfeeml-albimk heterocikloalkil: heterodkfealkimlkiI» heteroeikloaikenll leierodktealkenil-alkil, heterocikîôalkeblFai.k.eml heteroc i k ! oa I ke m I - al k i n i I arilaikik ari kalkend, arikalkinil, heteroaribalkil, hetemarlkalkenil heieroarikalkmik alkoxk elkloalkikoxk alkii-tio, eikloalki-tlo, szulfamod, sMlrinamotl aîkiRatnino vagy elkbalkílmmino, amelyek közöl mindegyik opdonálisao Myedesttve van egy vagy több sanbsziltoenssel a következők közül választva; Rg Rs és Ré jelentése mind egymástól függetlenül hidrogén, alkik alkenik eikloalkM, hetemcikloalkíl -0(0)-alkik GtóiÖ-afkii, “C(ö)-cikloalkik -CtO}M-alki!, karboxi-alkil, •CtObaiki-GpÄ R:(()ValklbC(()}NmlkiL -C<0)N--arü, -S(0)ra!kíl -S(Ö>-a|kh, ~St<))2-arÍ, *S(0)2M-alkÍk -SfÖbaríl mh beteroaril alktbartl vagy alkik heteroari, amelyek közti mindegyik epcionálisast helyettesítve van a következőkkel hidroxi vagy egy vagy több balogén, vagy Rs és R?> együtt a niirogénatommal amelyhez kapcsolódnak, egy hetetoeikloallil gyűrűt képeznek, ahol a nevezett gyűrű opcionálisan: helyettesítve van egy vagy több aíkd csoporttal R? és R* jelentése mind egymástól függetlenül hidrogén, alkií. eikloalkil, álként 1, heteroaríl, heterocikioalkil karboxi-alkil, kavbarnoil-alkik aíkíl-oxi-alkii, aíkenii-oxi·· alkik aril, aribalkik alkil-aril, heteroaril, heteroarilalkii vagy alkiidteteroaál amelyek közül mindegyik opcionálisan helyettesítve van egy vagy több szabsziinepssel a kővetkezőkből álló csoportból választva; hidroxi, halogén, oxo, da.no, alkil, eilkmlkil i\o" , , K ,n k hete mr wte o, :k <vjj ű, vu tlű Sd>o \R Rf , \C;0 alkik -CtOlN-alkik -NOÖ)Ö-aikil -OC((»N'-alkik -NDOiNRijRrj. -NRnSÜralkil. ^S(0)-a|k||v vagy R? és R« együtt a titrogénatommai, amelyhez kapcsolódnák, egy teerodMöalki} gyűrűi képeznek, ahol a nevezett gyűrő opdonálixan helyettesítve egy vagy több alku csoporttal; 1¾ jelentése hidrogén, halogén, hidroxi, alkoxi, kar box; vagy trihalogén-metil; X és Y jelentése vagy C és N illetve vagy € és N; Λ jelentőse aril, dkloalkil. cikíoalkenü, belemard, heterocikloaíkií vagy hetmx'ikloaíkenü, amelyek mind opcionálisun helyeutsítve vannak egy vagy több szitbs/timenssel az R^-bol álló csoportból választva; R.j(> jelentése hidrogén, dano, halogén, hidroxs vagy oxo, vagy Rjo jelentést· alkil. clkloulkiL alkotni, atkinil. aril, heteroarsk ciklonlkü-alki.L dkloalkii-alkenik cikloalkd·· alhtoíl, eikloalkenil'álkíl, ctkioatkenil-alkeoll, cihloaikcmi-dkiml. heierocikioulkíl, hete-oeikkviikend, hemrocikloaikeni-laikil, heterocikloalkenil-aikenü, heterodkloaikenil· alkinil, arif-alkif. ári b;d kend, arikaikinil, heteroaril-alkil, hetemen1-aíkenil, heteroanl·· alkinil, alkoxi, eikloalkiboxi, alkil-fio, dkíoalkil-tio, -SfO-alkil. -SfOí^-alKnl, s'tufámon, szulfmanu'íl i (Ok)Rí, (\0'>R, VR,R<„ -alktl <VNR',R(,}. Cikkxvisl (Nl-RR >, •dUcalMhalkil-tNRiRd. aikli-mkledkri ;NR R;u, -Ctt'nNldR,, nűkd{Ct(>íNR;R . -cikloalkil -(OOjNRyRHk -ctkloalkil-al ki Mö ÖIIN R?Re ) vagy -aikü-cikkulkd R'.O'NR Rs), amelyek ho/ul mmdoexm o.x.onal mn heha;exu\e tan ogv xagy több szabsz·! tuemssd a következők közül választva; Ru Rn és Rja jelentése mind egymástól függetlenül hidrogén vagy alléi; és annak gyqg|szerészetileg elfogadható sói, bidratiai. N-oxidjai vagy szol válj at, 2* Vegyület az 1. igénypont, szerint, álfol A Opcionálisan helyettesRve van Riç-ek ahol 1¾¾ jelentése a hidrogéntől eltérő.
- 3. Vegyidet az 1. igénypont szerint, ahol A jelentése: opcionálisan szubsztituált aril. 4 Vegytllet; az; I. igénypont szerint, ahol A jelentése opcionálisan szübszÄait fond vagy opcionálisan szubsztituált indanil.
- 5. Vegyüld a 4, igénypont szerint, ahol Rlt, jelentése dano, Italogétt, alklk m% heteroart, Nzultamoil. < VOIR „ <.\0}ÜRa -NR Rs„ ahol R<, Rs és R(; jelentése az, ami az L igénypontban van megadva, 4 'Vegyidet az !, tiÉtypöni. szerint, ahol A jeleatésc opctonâlisan szubsztituált heteroaril.
- 7, Vegytllet a 9. igénypont szerint, ahol A jelentése opcionálisan szubsztituált píridil, opcionálisán: szubsztituált benzofurattiL opcionálisan szubsztitualt 3K~izohenzoiurán-1-on-il vagy opcionálisan szubsztituált 2.3-dihidro-lzomdoR.í on-il, % Vegyidet az I. igénypont szerint, ahol A jelentése opcionálisan szuhgziíuáit heterocikloaíkií vagy opcionálisan szubsztituált heteroukloalkenil. % Vegyük? a 8. igénypont szerint, ahol A jelentése opcionálisan .sznöszrimáft piperidtmí vagy opcionálisan s/nbszutuáít piridazinil. It, Vegyidet a 8., 4., 6., 7„ 8. vagy 9. igénypontok bármelyike szemű, ahol Rr> jelentése hidrogén, ciuno, halogén. oxov alkil. alkod, dUoalkil-osi, -S(O)-alkil. •StOV-alkil, í\0)R», OOtüld, -GONE. Ra, «hoi Ka, R7-c-s·R» k'Luiícnc. az, ami az !, igenx potubau van megadva,
- 11, Vegyüld & lő. igénypont szerint, ahcsl Egy jdenlése ciano, halogén, pxo,; alkil alkoxí vagy OOjRs, ahol R* jelentése az, ami az 1, igénypontban van megadva.
- 12. Veeyület az előző igénypontok bármelyike szerint, amely a kővetkező la képied:la Rä., &2.ΒΆ jelentése szarni m !, igénypontban yaniSPgitelii'ozva, Mi Vegyidet az 14 L igénypontok smdy a &ÈWe$æ*ô· íb képlerü:ahol Rs. R: és A jelentése az. ami az 1. igénypontban van meghatározva. 14 Vegyület az előző igénypontok bármelyike szerint, ahol 1¾ jelentése opeionábsan szubszutuak Cj.reMI vagy opcionálisan szubsztlmalí Cygnikloalkik .11; Vegyület a 14, igénypont szerint, sM-% jétente-opNii^ ipteÉaát dklopropii |4 Vegyület az előző igénypontok bármelyike szerint, ahol R3 jelentése balogén, üfe cl kloalkil, heterodkloalkil vagy oxo. |f|. Vegyület a 16. igénypont szerint., abollEy jefebésn alktí vagy heieroclkloalkih 14 Vegyület m előző igénypontok bármelyike: szerint, ahol Rí jelentése balogén, hidroxl vagy damn vagy R, jelentése NR5RS. -ClplNRïRs, -COOR?, 4^€ίΟ}»£χ, -#ÖiO)NR7R* -•(XXO)R^ -NC{0)R·;. ŐR;, ^C(0)OR3, -NSÖjfe -SÖ2A% -SO^Rs. alkil, eíkloalkil, dkioalkil-alkií, heteroctkloalidl vagy heteroelktoalkilmlkil amelyek közül in indog} tk opcionálisan helyettesítve van egy vagy több sznbszthneossel a következők közül választva: R<g ahol E3, Es .Ró, R? R§. és 4¾ jelentése az, arái az előző igénypontok bármelyikében van meghatározva.
- 19. Vegyület az előző igénypontok hiOTnlyike szerint, ahol R4 jelentése hidrop vagy ciano, vagy R.< jelentése -CíO)NR-?Rfc -COOR·;. -NR,C{0)NR7R8, <K{0)m^ 4C#Q)R?> •ÖRt, -NGOöRí, alkil, amely opcionálisan helyettesítve van egy vagy több szabsztituenssöl a következők közül választva: R«; ahol R$ jelentése hidrogén, halogén vagy hidroxll, és ahol Rg, Ry ék :1¾¾ jelentése az, atni az előző tgényponmk bármelyikében van meghatározva, Ä Vegyület az -előző ifébypontok bármelyike szerint, ahol Rj és 1¾. jelentése mind égymástöl függetlenül hidrogén, alkil, alkenü, cikloaíkü vagy hetemdkloaíkü, vagy 1¾ és Rí> együtt a mbogénatommal, amelyhez kapcsolódnak, égy hetetoclkloalkil gyűrűt léptnek, ate! a new*·««: gyűrő opeionahsan helyettesítve van egy v&gy több aifól csoporttal.
- 21, Vegyül et m elűző igénypontok bármelyike szerint, ahol R? és 1½ jelentőse rnind egymástól függetlenül hidrogén, ailil, d&alfetl, hemrocikioalMh vagy alfceerl-oximlkíL amelyek közli mindegyik opcionálisan holpoesitve vas egy vagy több szubsztuuenssei a következőiből álló csoportból választva: hidroxiu balogért, oxo, crane, alkíl, cikloalitk alkoxl, aril, heteroaril. heierocikloalkil, -vS(Ö.)>-afiíi -SíOb-NRuRus --NQOValkil, -CíO}N-aÍd!, -NC(0)ö-alkii -0C(0.}N-alkik -NR-SOrattók -SíÖI-aikik vagy R7 és% együtt .a nitrogénatommak amelyhez kapcsolódnak, egy hemrodkloaSkii gyűrűt képednek, ahol a nevezett gyűrű opcionálisan helyettesítve van egy vagy több alkiI csoporttal; ,&jhl Rs t Is Rís jelentése hidrogén vagy €;..;~aikil, 3M, Vdgyíllet m előző igénypontok bármelyike szerint, ahol R-; és R* jelentése ontsd egymástól Rlggeílertil hidrogén, alkil, dkloalkiS. alkenil-oxí-aikil, amelyek közUl mindegyik opcionálisan helyettesítve van egy vagy több szubsztúuenssd a következőkből álló csoportból választva: hidroxt, oxo, cumi), alkil, eikloaíkil alkoxl arü, heteroaril -Síüli-alksk *Sv(*'' NR R-v· -NCíObalkiL -NR·. jSO^-alkil. vagy R-? és Rs együtt a nitro,aénatommak amelyhez kapcsolódnak, egy beteroei kioatkíl gyűrűt képeznek, ahol a nevezett gyűrű opcionálisan helyettesítve van egy vagy tbbb alkil csoporttal;;; ahol Rn és Rje jelentése hidrogén vagy Ci..r^k.li
- 23, Vegyidet az 1-22, igénypontok bármelyiké szerint, amely a követezőkből álló csoportból van választva: 2-cikiopropi I-Bonetox :>. 2 .meukíeudb[ i ,2,4bria >oloj I ,ő -alpirsdin,. 2<:)klopropii-8;-moioxio)-tenll-:[ RS^jtriazctlol' 1,5-a jpiridi», 2miklopropiRBonet:oxi4d4-meioxRlenIHb2,4jiriazololl ,5~ajpirnin, 2~ci klopropi I -B-metox i · 5 · i fr i fI urn-metl í -- feni í ) -11.2,4jtnazoíoí 1,5-alpindin, 2mlkk)p:ropÍl-Ő43,4-dimetoxl~fenfh-8-'rnetoxiii,2,4]tr!azoio[t,5-ajpmílirp imikitípröpil-b-rneíoxi-őoioten^óidbz^ltriazoioblJmjpíridln, ^-13~(2-éÍklopöpíl-S-metoxi-|l 52v4]triazoioí i ,5m|píridin-54l)-4ennl]-acctamid, 2mÍklopropiÍ-8“moioxi~5~p4bfíuorm)etoxi“leni íld 1 J,4|tdazolo| 1 vS-ajplridin, 2mikk>propih-8nnetoxi-5-(3onetoxldenil}4 1,2,4]mazolof LS-alpiridin, Id4d2miklopropib8'metoxi-|l52,4jtriazi)loi l,5--alpirid:tn'5;*i!j-4rotem2-lljsetanpn, 2<;iklfun'Opil-Snnetoxl%1-pinmidn)-'5dl41,?z,4jiriazolol t,5c)|prridin, 2mlklügix>pll~ő43-raetin"szalfoa!l'fend}^ hlv[342miklopropll-'i-tnoipxb[ 4,2,4]ΐπηζοίο|1Jmlpiridi?)-5 ólhiőmljohetart-szulíomnnid, 3*{2-cik1opropil-8-metoxi-{ 1,2.4jiriazoio[i,5-ajptrklin~5ôlhN-meül-te^âmid, 2-dklopropü-8 · metoxkV 4-acetiî-feml }-| 1,2,4 jtriazobj .1,5-a jpiridin, d-|Oa;2-ciklopropii'-8'ine?e!xi-j.b2,4]triazok>! !,5·a jprrídin-5-il)'léiül j-acetamid, B-(2-cikiopropíl--k-metoxi"n.2}4}tríazolo| l,5nctpiridin-5~itVbenzoésav-metil· észter, 2”C'tk!opropil-8-rnetoxi'5'pirídin-3-ii-[|,2,4|ma?.i)lo| kS-alpindin, 4-42-ciklopropü'knncurxi~[l,2,4]triazolo| 1,5-a|piridin~5··ϋ>·beozoésa v-meti!·észtotv 2”Ciklopropil-5-(4-metán«szulfbniÍ-fenÜ)-S ·motoxi··! l,2,4]triazolo[l,5-a]piridin, 2~ciklopropd-5-(2-tluur-fenil)--8-metoxi· [ 1.z/tjtfiazolol 1,5-ajpirklin, 2“Cildopmpii-8-metoxi-5«{4>-(2-metoxi-etoxi)-tonilj~i. 1,2,4)triazoIo[ 1,5mjpiriilirn 442-ο.ίΚΙορΐΌρίί-8-.β)ειοχί"[ l,2,4]triazoloi' 1,5~alpiridin-5-ii)-benzannti S-{34kjs&x.í^ <2,4;jtôafûk>| 1,5^JpirÄ>. S^lkbpropikldidluor-fenil)-^ i ,2,4Jiria?x'doí l ,5-ajpindtn, 2~cMof ropll--S*ffiMPxl-5-:pMá!4"4 4}-P ,2,4]fría^olö|! ,5--aipkiÄ, 2-©|klopropi!--5-42:>4-díkIér^lfePii!"8-metoxi"j 1Jkfkbmtaf I v5*a|pirídi«, ^iM0pr«^U-8-mëMÎ*5d'4-|»^oHn^4-szttïfôftîïHéÂiï3-| ! .2,41rna?olol 1 ,8 -alpMdb, j4-P~|2-cikioprop!-8-meiox{*| l:í2,4|iriazobÍ U1-a)pjriáia»5-i í }-henziíl -acetamii, :^4442-ci kiopropïï-S-meioxî-| í <2,4|írlax«te[ I ,5-aj pi cidiP-S-i 0 · be n a ü }- metán-szblknmnd, :2<íkiöpropiío44-Íiior-fo?üij''8~JtteU)xi"( 1,2,4 (tnazoiof 1,5«ajpiridin. 442*#k!opropi«^metó~[Í *2.,4|triaxoîo| i »5~a)pindin«5"il)-benz<.mitril, 2-[442-cikloprópjí>B-m<íioxi41,2,4)tnMpfc!l,5--a|piridin-5~i!)4enil|~prup!öasaV' metil-ésxter, 442mikbpropt!-8»mebxHbMltriazobjiJ-alpiÄ^ szulbnamid, 3<2-eikiopropiJ4$-meíöxHlA4]t&a^ 3r(2-cikiopfopH-8“in€ÄH^Ä4Jii«i^föC^5-a}j»Än“S-i!}»bestesl§wf :[3-d2<iklop!X>pik8anetoxi4 k2,4]tTÍaxpb[í,Sa|ppd3n*-54t)-fepil~pé|»)L 3“{2:«dkl.oprcjpt}-8-metoxi-i 1.2:,4]tn^öb|l 342-eikk>pn.>pi b S-tnetoxH í ,2,4]iria?ol0|i,5-:ajp{ridin-S-Íi)--ée»xaffi|i:, 4-(2-cjklopropil~8anetpxP|J52,4|tóaxolpIÍ,5-a]py(lb-'5'-i(}”l)en:Xöéaa^ 4<2~cíklöpmpi!-8-:metí?xl4d,2,4]töax(4o|!,5-alpbdÍft~5-ii>-NíN-bleil-be»zamíd, A42-dkIopropi I - S-tnetoxi 4 1,2.4]ma?oíö{ L5-ajpíridm·-5-itj~N -roebí-bónxaroid, 2- ciklopropil"8"metoxi-5-piperi<ii«-l“»{-{L2t4]if!a2:o!ofI,5-a]pindm, Í"í3-(2-cikiopfopil-8-hidroxi-p.2,4jtría?olo[1,5-a|pindin'5-ü}*teni))-etu©í-«i> 2d2-ciklopmp?l··8··n1etox^[l>2,4jU·i«i^o{oΓi,5'a]p'iridi1v·5·jlH¾«öikod:8«îtrí·l,. I · {5-{4"Ciano-feaiD'8-rneioxi 41,2,41triazoio[ ! ,5-a}piridir:-2-i 1 Nlkfepioplii" karb<.xasax^ti:!"Csx!er, .14 544-dabo·· féáÍi>-4anöí0X:í44,2.4páax0!op ,5-a|:pkMm-24I]· -ctkfopopan-karbonsav, I - ; 5 - (4 'Cpía0-:l4nilr8~o$etoxj4 1 s2,4jtnazobj 1,5"a)pindín-:2-ií Indkiopropán· karbonsav-amid, l45-s3”ciöno-píddim84l}-l-metoxi44>2,41:maxöio|lj~alplridlm24lpcikbpröpán·' karix>nsav4'xopröpH-'amí'd, 3- [2' i i-bidroxbnîoîiocikiopîopllbd-înoîoai-f 1,2,4MámÍ:Pii,3>'á|pydm“34ii|-benzonitnl, pirrolidin-1 -karbonsav- 1· |5~0-c»ain>-U'nil'-8 metOM-l *'2,4jítia/uk»[ 1,2 <dpirídin-2~ ü i cikíopropi ! -ni ebl-észtet, kopropi}"karbajninsaV“l45>{3^j^pr:|^nÍ:)*8-í^Mi-{is24]trixm>l^l>5~á:|piri.din^2-· i 11 -c iklopropi ! ~ me ni · és? tor, 3"|2~(:i-benxilöxi'irmüi-e1kk^r(>pi !>d-mef ox i 4 i -2,4] tri.azolo| L5 - a | piddb -541] ~ benzoniíril, N-l 14543<iano-'fcnii3d“sneföxi41,2,4|«iazo1oí S,S-a]pindin-2d^ kobubmraid, 14-|543-oiano-kdü)~8-metoxi41,2,4]lria?p1oI t ^5-a4pí?iclo-2-j 1¾ ^ci^lopíópí 1-ïïi=st01 -karbíapin sav -add openbi-ész tör, pírroUdin·' i~k.arhonsa'v~{ i- j5-f3-piáíi0»föiii|-8sÄtoxl-( 1,2.4j töözolol 1 J$-ajpiridin-2-il|-eik1opropil-meiii Î -amid, b<2-<ikioprop:M--B:--metoxi-[lJ,4|lMa«lö0,5--a;p!ridisv-5--il}-5~TVieüi-4,5-diiyáTO··®· pi.ndazin-3-Dö; .5 · (2”CÍklopropil-8«meíoxi-( ls2>4Í*rtoM í J-^]piÄ-5' il i-nikoiinoÄII* S-lS-ciklopropibS-rneioxl · {! ,2,4)triazoloi í 3-a|piridin-5-ii S-i ndán-1 »oft» 4-(2-cikk>propil-8-meíoxH 1,2,4 jmaxok>| 1,5-a Ipi ridin-5-il) - 2-i^setà l-'-bêa^SïÂÎt 4d2--cikbpropil-B"Tv;esoxid K2,4|iriazcdo|i J-«lpirídib~S4!)dndáíKÍ~»? 3-(2-ciklopropii*8-nunoxl*i ! ,2,4)5rlazolo{' I 4"v2-ciklopropil-8«metoxi-{ I .Saljiriaxoio [ Í 3-a)pto»-5~i)*241öCir^e»zoPiÄ 442-ciMopröpÍI' B-ffîetoxi ( 1 ,2,4]uiazoio{ I ,5-a|pMdiîî-S -M>2^©iöxj-lseazöfvEn Í, 5·(2·οίκ!ορΓορ?(-Β-Γη«.Ρ>χ5^1ΐ23]ίΠ3ΐχ>1ο[ί3~»)ρΐπΛν^54ί.ΐ-3Η-ί;ζοΡβ«ζο.ί«Γά5ν bon, 3- (2-cikiopn>pû'S-îppbîx|-i;l J^ltriazölof 1 benzoniirik :H2-ciklopropil~8-mek>xMl>24)triazolop3“a3piridiri-5~il}-5-metoxi-be«zottitnk 4- <2 -ci:yopïopiI-8-0îfê»5“|; 1,2?4JtFïas£Î>ioC IJ -aJ piridbs-ő-ií )-3 Mkxbboakjídfánl-op, 542-cíkíopropib8-meb>XHÍj3ltó4Zo!o|I J-á!pííM;i:0-5-dx23-dibyroázoWpl-Í~o0, 1 ->|8-ï»etoxi-5 4 i -0X04pd4n-44I^[ l J3^n^0ÎP[;13-a|pindin-2dll-éikibprôpâ0-karbonsa v-ben zi 1 - ami d , i4SH^<ia«o-piridi«-3-dy"Í"i»btöxi''|l I 3~a|pddk^ karbonsav-benzi l-amid, karbbaaav-eMöbexiy fBetíImrbíd, 0;5··(4<5ηπ(5-30τ^ΐοχί-ΙρΡΐΙ)40:00?0Χΐ433,43ί^ηζο!ο|13-η3ρίιΜΜ-2~11^ρ^Ιρρΐρρ8η·' kai bonsav-i zopmpi I ·ανη id. 1 · 1S ancHox.k>< i -οχο-indán -4 41 ; |· !2.4]triazoio|i,Sodpáidin~2-ii|-cik(opropán·· fcarboma v-cikiohexi l-roetü-amíd. i 4544-ciano-20netoxi-tenjl}'80ncíöxÍHd.23!fdazoÍ0ÍpÍ!:3-.a]piriiin-2:-4i|--eiklPprppÍln'· karbonsa\42·meíán-s^ldf(.adl·etil)-a.ffîidí ld5--{4-ciano-30m0ppd2ínin-8npetoxi-{l3'^driazolo[Lbov|píndhv2-i})“CÍkiopK'>páp·· karbonsav-ben/ü -amid, 1 -[8-metoxi~5-{ I -oxo- i3--dibid0>kobenz0ibídmSdl )-[ 1.2,43ídazo|Q|Í;5-a3piridin”2-íl)-ciklopropán-karbo»^v~b^£Í!“aiBi4 i-í 8-?netoxi-S-4l -oX0-mdá0-44l)-f 1,23jÄzöib| I J“aipiridíP~241|~cikl0pmpán-karbonsavdzopropikamid, i:~ÎSnneioxio4i'-oxodndân'>§^ài}dï3<43ibaz0fe|bJ-a|piridÎm2-i||'aik:iop0jpln- karbonsav--izopropi!-amid^ id8~meíoxi-5-U -oxo-?ndife'"5“iÍ)4^2»4]bdI^íáo|!i3~á{pindin-idl|«eikl<^SlPpá^í< karbona * -benzikannä. ::1~[8-ιηοιο.χ1-.5-ί Imxo4ndán-4dl>dií23]biazp3ö|l3^|piridin'-24l3>^fck:}propáH'-karböns3v--(2arktán-'SMdbnii'-efiií-amid, 1 -[B-meioxi 1,2^4 Jldazolof ! 3 -a3piríd!n-2-il|-óifelopropán~ karbonsav-|2-nseî|o-8Xôlfofnî-edi)-amid, I -15-(d-sianO'piddin-3~li|-8-mgtoxi-| 1,2,4|i;riaz0lo| IJ-a|piridín-2-il|-oikk)propan-kar bosixí»-dk lodex meiba mi d, !45''(5-'Ciaao-p5rklin--3-ii^'8-'metôxi'-|l,2;4]mazoloi i*5~aj;pM<îï«r2-ili-dklo:pfC^îàiï” karba?iS3vk2--me?-án”SZü]foiíil-etlI)--aínki Í-'{8--metoxi'5-(l'OaO'4 2v-dökdrökzöbeívzoferá:n:'5-iI)kl,2.:4]ínazo!o[l,5''3|píri<j;b-2' í l }-cikl-opro|>ân·· karbonsa v 42-dimetií -sxa Ifamoîl- eu t.bamid, I-|'54\1-α8Π0"ί0ΤΗί)-8'"ΐκ«ίόχΙ;··| I Ä^cäszoiol 1,5-a|pírldiu-2"ill“.C3ktopropáu-karbonsav -eb kész ser, I -[5»{4~dam>femi pS-mefoxki I ,2,4 jíriazolüj 1,5-a|pirÍdÍH-2'ál;j:--crklopmpáo·· karboftsav-etd^ászter, Ï-[S^S-aeedt-teml^e-mieio-xl-fl ^43-ttîâJÂOÎOiI Ï »S-alpiridtn-^-iil-ciMo^ropán-karbonxav-e ti i -észter. ( ,2,4]tríaxofoí 1,5-a}piddm·24! j-cikíopropém· karbonsav, j..p..(4-eiano-feníl)~8-tnetO:Xi-ÍL2,4|tóazol:o(!,5-a]piri:dirn-2-iÍ]-cilclopropán·- karbonsav, H543-aceid-idni!)-8-raetoxH 1,2.4|mazoiof i,5-a}pmdin-2-kl~ci::ktopropan-karbonsíiv, i--p-(3-ciaíío-iéniO-8-mek)xi--|!,2,4|tnazofo| ! J-a]pirfdin--2--ii|-oÎfeIopropâo-kafboimv-izopropü-awűd,. ! -[5-{3-íáano-femO~bonetoxi-ii,2,4'kriaado| !,5-a|pirk1in--2-il)-cik!ofmrp:án~ karbonsav-(|bndki-3-i!-Tneíi!}-aa'íki 3 -18-metox 5-2-11-( mor-bi í n - 4 - k ar bon i 1 Hűé lippropil }-1 ! .2.4 jinazoio- í ! ,5- ajpirkJin-$-ili-beozonitrü, l-i5-(3-eiano-iend)-8'rnetO:d-|l,2,4]triazolo|L8-alpiridin--2-dl-ciklop5vipaft-k arbonsa v - benzb-amid, 1454 3--eianö-íVni!)-8-meíoxi-( 1,2,4 |tria/xdof 1,5-a jpindm-2~di-eiklopropán-karbonsav-(2-szulfamoii~etü)-amid, I - j 5 - ( 3 - c iano- fen U) ~ 8 - me to x i-[ L2,4)maxotof t, 5~ a ] piridi »-2-I] -dk! opropáo-karboma v -< 2-roetán- szültem! l-eül i-avmd, 3- \ 8-metox i - 2 -[ !-(phroUdin- ! -karbon!!} -eíkiopropilM 1.2,4|tí3azolo| l ,5-a.]ptríiiift-5-ií)-benzomtfíL 2~meti0akrilsav-2-(t !-15”(3-ciano-'feí5ÍO-8-?netoxi-ü,2,41tri:azöIcríl,;5-a|pirídín~2-ií|-ci kopropán-karboni I ? -arnínoKüJ-éazter, l-|'5-t3-eut?to-fenk}-B-r5ietoxi~[L2,4jnia.zoki0b5-a]piridíV5-2dÍ;!-eik!opropán·- karbcmsav-í2-meto.x?-etií>aöíid. i-|5-(4-da:îo-temiï-8-meîoxi-i i.2.4knaxoioí 05-a)pindin-2--iO-C:k!opropao-karhonsav - (piridtn-341-meiil)-amidv 4 - {8-metox i-24 1 -(4-nietil -piperazin- l-karboni {.)-eMopropíl!-| 1,2,41îriazo!o( 1,5-a|pÍridm- 5-iip-benzonlt.ril, 4- i 8-me?:úxi-2- [ i ••(•morMin-4-karboftü)-ciklopropUl~( i .2,4 ] triaxoioí l ,5 - a jptndin-5-dj-benzorntril l -(5-(4-01^0.04^.1)-8--01^,^-11 J,4|tóazolafd ,5-a!piridin-24t l-ctklopropán-karbansav-benzíl -amid« i -('5-(4-ekm>tenii|-8-metoxi-|‘ 1<2,4]ínazoiof ! ,5-a|piOdisv-2-ií|-eik!opropasi·-karboíi&av-(2.-szultamoi I -euD-amiá, 1 -[5-(4-eianO“íend)-8-ioetoxi-[ ! ,2,4}triazoIop ,$-a|pMdk-2-i]-ci:kbpropáu~ karboasa v~( l-metáíKSZulfooi I · eu ! }-am Id, ! *[5~; 4-ciam>-feni IV 8or*eio;xb|t ?2<4Jrrfyzoloi t .*S-ia;jipi ri^í|j«:-^-lt!:-cífel<?pmpáín-karbon sav-i xopropil amid, ]-{;3-(4-ciano-l^«B>~krmete:i4lÄ4ltriiMlö(liS-aI|rlnÄ^i|^ilkl^po.p|Rr. karbon.sav~metil~amid, 1 ~[5-f4-ciano-feni !}- 8-metoxi-{ .1,2.4 jiriasoio{ 1.5--ajpiridin-24lj-cikk>propao-karbonsav ••etümmaL i ”[5-i4«ciano-íeni} ?-S -metoxl«! karbonsav-propd · amid. I -[5 η 4-ciano- fend) -8-meioxi~f 1,2,4]ΐπίϊζοΙο| i J -â3^rMîi^2ri:|^|ihaprQpâi^ karbonsav-dkiopropil-ai'nid, l«|^4-cjam>“fenii)-8~meroxM’l ,2;4 ]4Íaplbf I ,5 alpíridin-2-s! j-aklopropln·· katfeassav mrobmi ( -amid, ^j;S44<íyíH>fenü)-S-metoxb[iï2,4|¾iazoIop,5-alρi3Mr^2-äl··cík]όproplm karhcma a v · c i ano- men Î - ami d, í-{5-f4c5an°'fe^Ö-8-meto>ii-{lJ,4jíríazüié[I,5-a|piridm-2ftríjvcíi£lopn:>pán-' kâïfep»sav-(2-acetü--aminO“«îîi)-fï«i4 I-P-P-ciimo^fêdil^mfôtexHîJ^W^ol^XJ'âîifMÂ-l^iHikï^prdpân·· kartesa v-C2-œ©iimszali3ôîJ -ansno~eb I }$mM, !~í544-cian;o-feniI)-8-mefoxi-(IJ>4|tóaz0ÍöfÍ.S“aJpiridíb-2-ííij-eíklopi'opáp·· kartosav-(3-fÎK>rfobn4-ii'3<m5-pîopiIVajïîi:d, i - f 5 (4~ciavío-ieni 1 ï-8- merőxi-- j 1.2,4kriax oioi i ,5-a]pirklm-2i i i cikiopropá?}-karb©8sav'-(2.-dimeúl-szu!famoÍHiíii!3-smyt ! -j‘5 ·C4-ciaRO-te«U)-8-metoxi- [ i ,2f4|rria2o!p|i J--a|pindM-2--ii|-ai k!öpí®pán- ka.rboTisavd'2-(fnetdivs:rariíonil-írííd3Í-ímdnoH.íi:I]-aiap:d, i -{5-(3sureiü-feni i)-8~meâ$$M .1,2.4 itriazolo[ 1,5-a|prfdm^-i:VNÉ:ïopropà«"· karbon sí o-d. p b'i d i n- 3 41 - n icMl· «mi d, i a3-{8-menîxi-2~[ i-(4-anenl-pi:|5enizirb!-karlxi?nl)-ciklppropiHl 5oU--feniií--eíanoró 1- (3-{ 8-Tneíoxi-2>| I -(moiföÍ$H4felÉ^SÍÍK4:ktpp^^ íU'feni).oeíancm, I45~(3~aceíd--fenii}-8~níei:oxi-P:52:,4|tri:axo!oíl:,5"a|pMdirs^2:41]míkjopropáp- karbonsav-kmzikamkl, 1 ··( 5-(3'acehl~ffenil)-S:oneioxí-'[ i ,2,4]{ria?.oío[ i .3-a!píndm-2 - íí j-ei kiopropám karbí)naa\n öoszulibsnojimnij'-ainid. i -[ 5-(3-acetd· fend }-8-metoxi-[ 1,2,4]triaxoloj. í ,Sra|pÍridí:n42-IJ4<íklc^>|4^ karbonsava S-rneian-szubonil-eiiD-arnid.. 2- oíedi-akíilsav-2-({k4543-cía?íO'feoíi)'8-mcioxídl.2,4!mazoIo[i J~aj pioeiiíi- 2 ilj-inkoprí.vpán-karbonilkaniinokeui-esxteív |-|3'42-c^ö~fe?b^-S'brfötoxi-4:l52,4]:tri:azöio|iv3~a]píridiík24]kcíkippropáí3-karbonxav - i2-hidroxí •opll-amM, plkii>hexibkarbarmnsav-l-i545-Of:ano-ptridm^”i!>-8aBetoxk[I,2;4j rdMoiöil,5-a|pi:ndm-d-iil-ciktopropilmeul'eszier, propd-karbami «sav-148-met.oxii-54 1 -oxo-dndÉ^SdlM 1.2,4] iriakolo ;[ 1,5~a|piridi ndk II^ÎklopîXjpil^mebi-ésk dImed!-kartaínosav-MiS44-eia^ i.5-apfldin- i-dll-cíkíoprdpil-meííl-lagter, ;kopropíJ'-karba miÄ y~ ! -|S-{S~iiiano-pirpia-3-iï> SspteíPXi-f I ^jtriazíé^l J-ajpMdin-2-tl]<iklopr<>pii«rneîi}-ésiiôr>.. propü-karbaminsav -1 - í 8-f»ete|-S-tt^xo-Wá»r4"il)-Í l,2,4jíriaxoíöf I J-djpiridin-2- 1 íj -c i kiopropi í - meri í - észter, pim>ltdiíbí'kaAo*5sav~ I I .S-ísjpliclíí- 24i}^fkíöpr{)pd-íK©tll--észíesrv ·ίζορπ>ρΐΙ^8&α^ίη.χ8ν- 1 -íS-|4^aáú-3^tei-M ,5-aJiÉÂ'· 2-il l-dklopropü-metil észter, propil-karbarrnnsav 1 '[5-^<®ΐΚ>-ρΐη0ΐΐν3^Ι}··^··ΐΏρί%ί-[12ν^1^^0Ι^5~Μρ^ΐό- 241 j-cikíopropi l· tnetd -észtet, propil-karbansinsuv-1 -[ 5~< 1.^4-¾ 'Éï5-agiïÿk>i. í 2 -i íj-elk) opro ρ i i- me t ü-èszter, plteolidin-i-karbotteav~!-[8-metoxt-5-(l-imo4bdd^ 2-í]j~dk|öpropií-mepi-é^ter, 241} -cikíopropil-meíil-éezíer. aklohexit-karbamteav- HH-raetexi~54Í^ l ,2.4 juiazoioí 15-ajpiridin · 2-iljadkiopropîI-meîil-észter, eikiohexikkarbaminsav- i [544-eiapQ-3-ffietoxbtenlI)“8-mdpxr-Ii24jinazofoP J-a|pmdm” 241 ] cikiopi'opi l-rnetl i -észter, pirroíldin-1-karbonsav-i“|5-\S-ci ano - pirr din-3-ü)-S ~ό - [ 1 ^^jtmzöíölljP-'ajpmdín- S-íIJ-ciklopropil-meül-észter, dimeüi-karbaíninsav-1 ~( 8-metox 1-5-0 ·οχ04^έη~5-ίΙ)~ί[1 ,:2,4]ίίϊ4ζο!ο0,5-®|ριπϋίη·2-d l-eiklopropn meíii-észter, clunetn-karbaminsav-1 -j 5-(5-ekm)--pMdm-3-i!)-8-metoxl-jj ,2,4 Itríazoloi í ,5-afpmdin- 2- ii)-eik!opropi!-metil“észref, dietd-karhaodpsav-·1 ïbéd^ia^xO'rpetoxkfeadj-i-metoxkSikeJ ]táazo)o|l,5-a]pindte-2 bj - c 1 kiopropi í - met í I - ész tér, diebí-karbamímav-1 -( 8-ntetc«i-5-(1-oxö· rndé:n-4"ií)-í 1,2>4jpiazpíüi 1,5telpÍrídÉp041 j-dkk>propd~meii í -észter, ii j -ciklopropi!-meíd-észter, 5-[2~( i -hidroxï'tïteîË-plkipppapii plkodnonltríl, 4-C2-cikíopröpii-8--röetps:i-j .L2.4'jünazoíe>í i.5--a]piridin-84^2-iiu4oxî-benzoïùïdt, 4- |2-eMoprppd-|-rBet0xl-(i,2.41tfiuzoloiL5'a|pjrîdiïr8-ilr-2-metii-benzonîtrii 3- (2-C£kíopropií-5-inetoxí-[ 1,2,4)triazolo[ 1,5-a|piridin-8-il kbevtxímdril, 5- {2-dkf opropií-S-metoxi··| ) ,2,4jtríazoloí 1,5-ajpirídtn-8-i ÍV indán-í-söii,. 4- {2“Cikíopropii-5-metoxi-| 1,2,4jtnazok>( Í,5-a|pindín-8-íí)-tndán-|-p|t,. .Í>i8H4-cjanO"3-meíox$-renil)-5-metoxi-íh2,41triazoto(i,5'a]pírídíi“.2éUj-eiklopr«’ípÉt* fearböns&v-jztíprtípdrítteíid:,: Í-[3“nietoxi-8-(1-oxO"l,3-ddjidro-4zc)benzöktrán--5-ílí j 1,2,4]ínazoio|.) ,5-a}pjridin-2-IIÍ”dkopropáíí-karbonsav-kopropíj-ami4 1 -f5-ntetoxi-8-( I -oxo-indán-5-ι) M í ,2,4jtrtezolb|: l,l-alpl^#»-24ii*PÉteprop|n>· karbonba v dzopropü -amid, !-{5-hidroxi-8-( l -oxo-mdán-d-ü >-| 1,2,4|t4az0)ô[i4'-'ajpdidÎ0"2'4il-ëïkîopropâri-karbot tsa v ..\2opropd - a n t id. J4>mfíox5-S-<l~ox0--i«üáö:44íHl ,2,4 larbonsaV'-(2meiä»'SiidlonsI'e!il)<00Sii í-P-'(5--cíá0ó-piridí0--3<4O^5-metOT0:[l,2,4]triazolö|lí5-a||>íridi0-2-il-éíkiopmpáíj-' ;teboosav-(2-meÄ l~ P-meíoxi-8-p -ox o-indfe-S-11 >--p ,2:,4|triaz«kií 1,5-äjpindm-2-1 poikíöpropam k ar bon s av - ixopropí I - am i d, 1 " [5 ' meíoxi-8-( 1 -oxo- indte~541MÍ Jpjtnaxoiof ?;,S-alpiri:did"24í pGikiopropis-karbi n isa v ízo bu ü 1- am i d, l -15-m*íto\i-8-(l -oxo" 14-dlíddp)~iKobeíi^plurán-S-d H 1 JpfPiaxolof i,5 -älplÄs-S-tn<ákopropán~karb<'ínsavbxöp:ík>pi!-ami(I, I - [íM4-dano-3-nielox i - feníO-S-metoxH 1<2,4]tr!akölö[ í ,5-a]piridin-24! hciklopropám· karbonsa v · izo prop i I - a m i d, i-{8"(4“Cjaj3O"3~iTU‘toxi-fenü)-5-nietoxi-ii.2v4]triazolo|f,5*^|pmdi«“2-MH#Jopr0|[>ä«- karbonsav-iz^iieiarz-zzidfotiil-'etiOziSsisd. H5-metöxi-8-( 1 -oxo-indán-S-ijH i ,2,4]triappipf 1,5-¾ !pí:ddP>-3-11P C í karbGn5av~í2-rnete~szyííooií-edí)--amíd, I · [5-metoxί-8-í 1 -oxo·· 1,3-dthídro-izobenzofurán-5-Í'f}4 ! il!-dkopropán--karbonsav-(2-metáiv-szuifoni!-etíl0amid, l-|8-{4-ciun0"3~meU)xÍ>fenil}“5'-metoxi-[l ,2,4]íriazoío( LVajp» idín-2-üi*Ciklupropan-karbonsíiY-kíobiHib-aniid, H5*bidroxi-8~( I «oxo-j«dán»5*HH' 1,2,4jtríaK0lö[lJb-'aipindffi-4-4l|--cikloprópáb--karbons a v - í zopropi i - a mid, i'|8«metoxi^5»(b-ox0“i3“d^»dr0-izobenxofcräR-541i4iJ>4|y-Äife|'l,Si-'a|piTiidmil;- i))"CikopropánA'art>on&av-(20öe{ồS?ulfon8-^i}^aípi4 b-[g-rnei.oxi-5-í i-()xo4,3 diivid{x>-izobenz.oí:iH'án-5 íl}-(l,2.4jtriaz:ok.í{L5“a|piridin-2· ií|- cikqpropáa-karbomav·cikiphexü-mmJ-aajÄ,. l4^'fReiox^5Hri;*ox0“i3'"CßM^ö^l2Äi2^fuÄ‘S4!>p.,2,4I^Äk)CI ,5--á^mdin"2·· !lipGikopröpáp'kastK>nsav42-dimoíi4kbi:lamoib€t5!)-amid, ciklopropil4ïmtiI4szter, dlmefil-karbamiBsav-1 '[b-mefoxí-S-í: l-oxo·· IJ-dibldda-lzobeo^olbráa - J-i|· |!f2v4jtóaxóIo|l,3-ajpiridÍB-'2-4:Í|rpkÍ^ropií~oMl-ék2íop ilj-cikiopropil-oKdii-ésxrer, dief ibkarbarnmsav-· i ~f5-{4-ciano- ö-meioxi-feniÍ)-8 · moíoxkf l^dftezolol 1,5-alpíridte 241]- ciklopropi 1 -meb i észter, dMobexU-kai1>amimav>H8«metoxi-54l“öxo4,3-dibidr»fc^iäit^taiiä$^54l]^ [ 1,2,4 jtnazolof. 1,3-a]piridús-2-i; j-cdrkspropil-mebí-teter. 4-[2-{ 1 · hidroxi-méîiïi-eiklopropn}-8-meto\i · (1,2,4 (trmzolo{ ! ,1-a jpmdia-S-d] --2.-.metoxi-benzonttTii,; 4-|2-( i meto.xi-f 1,2:,4joteei 1,5 -a|pi <bmb4:|~2- meíoxí-benzonkriL 1-f5-(3-cia!io-fenir}-8-metoxi-ii,24!ínazoío(L5~a(pirk1iJV-2-.íl]cikk>propá.n-teltexav-ízobutil - amid, l-|3-:í3-eianü-lenii}"8~mptei-[iJ,4]íriazoiú|!,5'a|p]ridm-2-ílI-oÍklöpropár!!- kaíteosaív-(2-rneiáír'Xgd]foBd-aoBBO-oul)-am]d¥ ! "15-ί.3 'ciíiivio -feîïi!} -S -1 ^2,4 ftríaKoiol i 3ipitodki 2-îÙ cikíc>pr^3pán -Icarbonïîiv-'ÂçpF^ii-âiÂÎd» I ·· [ 5í3ciaíuvtení])~8-meloxi*[ 1,2„4jtriazoloj. 1 „S-alpi ridim2-i ! j -ciklopropáiv korbonÄ^ikiötoüiliÄlü-äiBid, 5~j 2-( I 4zi)b«íö^f~«íei!~ci ktöpropi]|-8-raetoai>| I ,2rilltltmoíöj( ! ,3-aIpirid(n~5-d jb nikotinom!, ril, 5-{2<$kio|H^piÍH5^tó41,2,4|rlazolot 1G-ajptrklin - 8-il>mikottnunltrik 11,2,4 ]{damIo|13'Slpmáii^24í]^dMopopáö'· karboosav*(2'dime!li'&zu1femoiI-etij'an'Hd. H5~í4"eían0dendo$-meioxH:i,2,4jtriazotöfÍ^^ 14544-Ä»Q-3“metOKi--fcBiI)-:8:-'meioxi"|:^2/!|tiiaiolu| !.5-aIpirklií^-2-ίί|-cikI<>propá^' karbonsav^^dimetü-sx-uííamoil-etílj-amid, i~r545^íano~píridj«-34i)~8-imö^HÍ.A4Ítóa2»!öÍÍ>5-:aípmÍlii-24i]<iklopSi»í)áft-': karbonsav · ( 2-dírneli 1 -szulfamoil-etif) »amid, ! -ÍB-meioxid-d-oxo-óndánő'úi-'j 1,2,4)íria^olo| I^-alpirldi0'2-iî|-éiklopmpâÈ^-karbonsav-e 2-dimetii-sztnÍamoi I · etil)-amid„ és aaiak gyogyszerészetüeg elfogadható sót, hidráyat,: M-oxidjai vagy mídvátjai 24, : Vegyitó az I-23. Igénypontok bármelyike szermt, terlpiábatuöriénő alkalmazásra..
- 25, Vegyidet az 1-23, igénypontok bármelyike szerion a kővetkezők kezelésében történő alkalmazásra: bőrbetegségek >agy bőrádapotok vagy akut vagy krónikus bőtseb rendellenességek {angolul: „cutaneous wound disorders"). 2é, Vegyilet á 23, igénypont szerint, a következőknek a kezeléseden történő alkalmazásra: proliferativ és gyulladásos bőr rendellenességek, pszoriázis, rák, epidermális gyulladás, alopécia, bötntrófia, sztemid által inclnkllí bőmiroím ffotöregedés, #sy okozta böroregedés (angolul: „photo skin ageing"), akné, dermaíitisz, atóplás dermatitisz, szeborreás dermatite* kontakt dermaíiiszs wtikária, prurilisz és ekcéma.
- 27, Gyógyszerészeti készítmény, amely tartalmaz egy az 1-23. igénypontok bármelyike szerinti vegyületet együtt egy gydgyszeréssetíleg elfogadható vivőanyaggal (velukolummal) vagy segédanyaggal (excipienssel) vagy gyógyszerészetileg elfogadható hordozóval foordozokkai.
- 28, Gyógyszerészed készítmény a 27. igénypont szerint,; amely továbbá tartalmaz egy vagy több további terápiásán hatásos vegyületet. Ä Egy az 1-23,. igénypontok bármelyike: szerint) vegyidéinek az alkalmazása egy gyógyszernek a gyártására a következőknek a megelőzése, kezelése vagy enyhítése céljából: bőrbetegségek vagy bőr-állapotok vagy akut vagy króoifcns bőrseb rendellenességek tangóiul: „.cutaneous wonnd disorders'3. Sík Alkalmazás a 2§, igénypont Szerint, ahol a bőrbetegség vagy bőráilapot a következőkből álló csoportból van választva: proliferativ és gyulladásos bőr rendellenességek, pszoriázis, rák, épidérmáis gyulladás, aiopéeia, höratróísa, szteroid altul indukált höratrófia. bororegedes, lény okozta ^,noieg«dés t,ne -sül photo -vsat ágért»· , uku, oetrunus Mópiás dermatitisz, szeborreás: dermatitisz, kontakt dermatitisz, urttkária. pruríte es ekcéma
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| RU (1) | RU2544011C2 (hu) |
| SG (1) | SG172206A1 (hu) |
| SI (1) | SI2379548T1 (hu) |
| WO (1) | WO2010069322A1 (hu) |
| ZA (1) | ZA201104422B (hu) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI1009637A2 (pt) | 2009-06-05 | 2019-04-30 | Cephalon, Inc | composto, composição e uso de um composto |
| US8283465B2 (en) | 2009-07-17 | 2012-10-09 | Japan Tobacco Inc. | Triazolopyridine compound, and action thereof as prolyl hydroxylase inhibitor or erythropoietin production-inducing agent |
| EP2343294A1 (en) | 2009-11-30 | 2011-07-13 | Bayer Schering Pharma AG | Substituted triazolopyridines |
| AU2010335656B2 (en) | 2009-12-22 | 2015-05-07 | Leo Pharma A/S | Pharmaceutical composition comprising solvent mixture and a vitamin D derivative or analogue |
| US20130039952A1 (en) | 2009-12-22 | 2013-02-14 | Leo Pharma A/S | Calcipotriol monohydrate nanocrystals |
| NZ600999A (en) | 2009-12-22 | 2014-06-27 | Leo Pharma As | Cutaneous composition comprising vitamin d analogue and a mixture of solvent and surfactants |
| WO2012121988A2 (en) * | 2011-03-07 | 2012-09-13 | Celgene Corporation | Methods for treating diseases using isoindoline compounds |
| SG11201402424PA (en) * | 2011-12-21 | 2014-09-26 | Leo Pharma As | [1,2,4]triazolopyridines and their use as phospodiesterase inhibitors |
| CN104822392B (zh) * | 2012-11-30 | 2017-09-08 | 利奥制药有限公司 | 抑制活化的t‑细胞中il‑22表达的方法 |
| WO2014206903A1 (en) | 2013-06-25 | 2014-12-31 | Leo Pharma A/S | METHODS FOR THE PREPARATION OF SUBSTITUTED [1,2,4]TRIAZOLO[1,5-a]PYRIDINES |
| WO2017089347A1 (en) | 2015-11-25 | 2017-06-01 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and pharmaceutical compositions for the treatment of braf inhibitor resistant melanomas |
| DK3642210T3 (da) | 2017-06-20 | 2024-12-09 | Union Therapeutics As | Fremgangsmåder til fremstilling af heterocykliske 1,3-benzodioxolforbindelser |
| WO2019079481A2 (en) | 2017-10-17 | 2019-04-25 | Conocophillips Company | GEOMETRY OF HYDRAULIC FRACTURES BY DISTRIBUTED ACOUSTIC DETECTION AND LOW FREQUENCY |
| EP3724196B9 (en) | 2017-12-15 | 2023-03-22 | UNION therapeutics A/S | Substituted azetidine dihydrothienopyridines and their use as phosphodiesterase inhibitors |
| JP2021155336A (ja) * | 2018-06-27 | 2021-10-07 | Meiji Seikaファルマ株式会社 | 新規pde4阻害剤 |
| AR114977A1 (es) * | 2018-06-27 | 2020-11-11 | Meiji Seika Pharma Co Ltd | Cristales de derivado de benzoxazol |
| GB202306662D0 (en) | 2023-05-05 | 2023-06-21 | Union Therapeutics As | Dosage regimen |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU705690B2 (en) | 1995-05-19 | 1999-05-27 | Kyowa Hakko Kogyo Co. Ltd. | Oxygen-containing heterocyclic compounds |
| WO1998022455A1 (en) | 1996-11-19 | 1998-05-28 | Kyowa Hakko Kogyo Co., Ltd. | Oxygenic heterocyclic compounds |
| US6514989B1 (en) * | 2001-07-20 | 2003-02-04 | Hoffmann-La Roche Inc. | Aromatic and heteroaromatic substituted 1,2,4-triazolo pyridine derivatives |
| US6693116B2 (en) * | 2001-10-08 | 2004-02-17 | Hoffmann-La Roche Inc. | Adenosine receptor ligands |
| US7763617B2 (en) | 2005-03-07 | 2010-07-27 | Kyorin Pharmaceutical Co., Ltd. | Pyrazolopyridine-4-yl pyridazinone derivatives and addition salts thereof, and PDE inhibitors comprising the same derivatives or salts as active ingredient |
| JP2007091597A (ja) | 2005-09-27 | 2007-04-12 | Kyorin Pharmaceut Co Ltd | ピラゾロピリジン−4−イルピラゾロン誘導体とその付加塩及びそれを有効成分とするホスホジエステラーゼ阻害剤 |
| US20090196284A1 (en) * | 2006-06-28 | 2009-08-06 | Nokia Siemens Networks Gmbh & Co.Kg | Method for Providing an Emergency Call Service for VoIP Subscribers |
| AU2007272009A1 (en) * | 2006-07-12 | 2008-01-17 | Syngenta Limited | Triazolopyridine derivatives as herbicides |
| JP2008024599A (ja) * | 2006-07-18 | 2008-02-07 | Kyorin Pharmaceut Co Ltd | ピリダジノン誘導体、それらを有効成分とするpde阻害剤及び医薬 |
| JP2008069144A (ja) | 2006-08-17 | 2008-03-27 | Kyorin Pharmaceut Co Ltd | ピラゾロン誘導体及びそれらを有効成分とするpde阻害剤 |
| ATE540037T1 (de) | 2007-04-16 | 2012-01-15 | Leo Pharma As | Triazolopyridine als phosphodiesterasehemmer zur behandlung von hautkrankheiten |
| CA2692249A1 (en) | 2007-06-19 | 2008-12-24 | Yasushi Kohno | Pyrazolone derivative and pde inhibitor containing the same as active ingredient |
| JPWO2008156094A1 (ja) * | 2007-06-19 | 2010-08-26 | 杏林製薬株式会社 | ピリダジノン誘導体及びそれらを有効成分とするpde阻害剤 |
| JP2009040711A (ja) | 2007-08-08 | 2009-02-26 | Kyorin Pharmaceut Co Ltd | カルボスティリル誘導体及びそれらを有効成分とするpde阻害剤 |
| EP2348018A4 (en) | 2008-09-25 | 2012-04-25 | Kyorin Seiyaku Kk | HETEROCYCLIC BIARYL DERIVATIVE AND PDE INHIBITOR CONTAINING ACTIVE SUBSTANCE |
| JPWO2010041711A1 (ja) | 2008-10-09 | 2012-03-08 | 杏林製薬株式会社 | イソキノリン誘導体及びそれらを有効成分とするpde阻害剤 |
-
2009
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- 2009-12-18 JP JP2011541089A patent/JP5743901B2/ja not_active Expired - Fee Related
- 2009-12-18 PL PL09795687T patent/PL2379548T3/pl unknown
- 2009-12-18 DK DK09795687.4T patent/DK2379548T3/en active
- 2009-12-18 AU AU2009328752A patent/AU2009328752B2/en not_active Ceased
- 2009-12-18 WO PCT/DK2009/000262 patent/WO2010069322A1/en not_active Ceased
- 2009-12-18 HU HUE09795687A patent/HUE027770T2/hu unknown
- 2009-12-18 RS RS20160308A patent/RS54752B1/sr unknown
- 2009-12-18 NZ NZ593595A patent/NZ593595A/xx not_active IP Right Cessation
- 2009-12-18 HR HRP20160488TT patent/HRP20160488T1/hr unknown
- 2009-12-18 MX MX2011006428A patent/MX2011006428A/es active IP Right Grant
- 2009-12-18 KR KR1020117016745A patent/KR20110094355A/ko not_active Ceased
- 2009-12-18 EP EP09795687.4A patent/EP2379548B1/en active Active
- 2009-12-18 SI SI200931410A patent/SI2379548T1/sl unknown
- 2009-12-18 SG SG2011044203A patent/SG172206A1/en unknown
- 2009-12-18 RU RU2011129786/04A patent/RU2544011C2/ru active
- 2009-12-18 CN CN200980156864.XA patent/CN102317287B/zh not_active Expired - Fee Related
- 2009-12-18 ES ES09795687T patent/ES2570769T3/es active Active
- 2009-12-18 CA CA2747022A patent/CA2747022A1/en not_active Abandoned
- 2009-12-18 BR BRPI0922452A patent/BRPI0922452A2/pt active Search and Examination
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2011
- 2011-06-14 ZA ZA2011/04422A patent/ZA201104422B/en unknown
- 2011-06-15 IL IL213570A patent/IL213570A/en not_active IP Right Cessation
- 2011-06-17 NO NO20110871A patent/NO20110871A1/no not_active Application Discontinuation
-
2014
- 2014-12-18 JP JP2014256695A patent/JP2015096535A/ja not_active Withdrawn
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2016
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Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0922452A2 (pt) | 2015-12-15 |
| DK2379548T3 (en) | 2016-05-17 |
| ES2570769T3 (es) | 2016-05-20 |
| CA2747022A1 (en) | 2010-06-24 |
| US20120028974A1 (en) | 2012-02-02 |
| ZA201104422B (en) | 2012-09-26 |
| RU2544011C2 (ru) | 2015-03-10 |
| JP2012512192A (ja) | 2012-05-31 |
| EP2379548A1 (en) | 2011-10-26 |
| SG172206A1 (en) | 2011-07-28 |
| NO20110871A1 (no) | 2011-09-19 |
| AU2009328752B2 (en) | 2015-07-16 |
| SI2379548T1 (sl) | 2016-06-30 |
| EP2379548B1 (en) | 2016-03-09 |
| HK1165791A1 (en) | 2012-10-12 |
| IL213570A0 (en) | 2011-07-31 |
| WO2010069322A1 (en) | 2010-06-24 |
| RS54752B1 (sr) | 2016-10-31 |
| KR20110094355A (ko) | 2011-08-23 |
| MX2011006428A (es) | 2011-07-28 |
| CY1117562T1 (el) | 2017-04-26 |
| JP5743901B2 (ja) | 2015-07-01 |
| JP2015096535A (ja) | 2015-05-21 |
| IL213570A (en) | 2015-10-29 |
| US8952162B2 (en) | 2015-02-10 |
| PL2379548T3 (pl) | 2016-08-31 |
| CN102317287B (zh) | 2014-10-08 |
| CN102317287A (zh) | 2012-01-11 |
| NZ593595A (en) | 2013-07-26 |
| HRP20160488T1 (hr) | 2016-06-17 |
| AU2009328752A1 (en) | 2011-07-07 |
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