HRP20180524T1 - Derivati tipa azaindazola ili diazaindazola kao lijek - Google Patents

Derivati tipa azaindazola ili diazaindazola kao lijek Download PDF

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HRP20180524T1
HRP20180524T1 HRP20180524TT HRP20180524T HRP20180524T1 HR P20180524 T1 HRP20180524 T1 HR P20180524T1 HR P20180524T T HRP20180524T T HR P20180524TT HR P20180524 T HRP20180524 T HR P20180524T HR P20180524 T1 HRP20180524 T1 HR P20180524T1
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HRP20180524TT
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El Bachir Kaloun
Karim Bedjeguelal
Rémi RABOT
Anna Kruczynski
Philippe Schmitt
Michel Perez
Nicolas Rahier
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Pierre Fabre Médicament
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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
    • A61K31/437Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/4985Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems

Claims (18)

1. Spoj sljedeće opće formule (I): [image] (I) ili njegova farmaceutski prihvatljiva sol ili solvat, njegov tautomer, ili stereoizomer ili smjesa njegovih stereoizomera u bilo kojim omjerima, kao što je smjesa enantiomera, posebno racemična smjesa, pri čemu: - Y1 i Y4 svaki predstavlja, neovisno jedan od drugoga, skupinu CH ili dušikov atom, - Y2 predstavlja skupinu C-X-Ar te Y3 predstavlja dušikov atom ili skupinu C-W, ili Y2 predstavlja dušikov atom ili skupinu CH te Y3 predstavlja skupinu C-X-Ar, uz uvjet da: ▪ najmanje jedan a najviše dvije od skupina Y1, Y2, Y3 i Y4 predstavljaju dušikov atom, te ▪ Y2 i Y4 ne mogu istodobno predstavljati dušikov atom, - Ar predstavlja arilnu ili heteroarilnu skupinu koja može biti supstituirana s jednom ili više skupina odabranih od atoma halogena, (C1-C6)alkil, (C1-C6)halogenalkil, (C1-C6)halogenalkoksi, (C1-C6)halogentioalkoksi, CN, NO2, OR11, SR12, NR13R14, CO2R15, CONR16R17, SO2R18, SO2NR19R20, COR21, NR22COR23, NR24SO2R25, te R26NR27R28 i/ili može biti fuzionirani heterociklil, - X predstavlja dvovalentnu skupinu odabranu od O, S, S(O), S(O)2, NR4, S(NR4), S(O)(NR4), S(O)2(NR4), NR4S, NR4S(O), NR4S(O)2, CH2, CH2S, CH2S(O), CH2S(O)2, SCH2, S(O)CH2, S(O)2CH2, CH2CH2, CH=CH, C≡C, CH2O, OCH2, NR4CH2, te CH2NR4, - W predstavlja skupine R5, SR5, OR5 ili NR5R6, - U predstavlja skupine CH2 ili NH, - V predstavlja C(O), - n predstavlja 0, - R1 predstavlja vodikov atom, ili skupinu NR7R8, - R2 predstavlja jednu od sljedećih skupina: NH2, NH(CH2)3NMe2, NMe(CH2)3NMe2, NO2, [image] , ili [image] , - R3 predstavlja H, - R4, R11 do R25 te R27 do R28 svaki predstavlja, neovisno jedan od drugoga, vodikov atom ili (C1-C6)alkilnu skupinu, - R5 i R6 svaki predstavlja, neovisno jedan od drugoga, vodikov atom ili (C1-C6)alkilnu skupinu, koja može biti supstituirana arilnom skupinom ili može biti supstituirana benzilnom skupinom, - R7 i R8 svaki predstavlja, neovisno jedan od drugoga, vodikov atom ili koji može biti supstituiran (C1-C6)alkilnom skupinom ili (C3-C12)cikloalkilnom skupinom ili može biti supstituiran heterociklilom, te - R26 predstavlja (C1-C6)alkilnu skupinu.
2. Spoj prema patentnom zahtjevu 1, naznačeno time da - Y1 i/ili Y4 = N, - Y2 = CH ili C-X-Ar, te - Y3 = C-W ili C-X-Ar.
3. Spoj prema bilo patentnom zahtjevu 1 ili patentnom zahtjevu 2, naznačeno time da X predstavlja dvovalentnu skupinu odabranu od S, S(O), S(O)2, NR4, CH2, CH2S, CH2S(O), CH2S(O)2, CH2O, CH2NR4, NHS(O)2, SCH2, S(O)CH2, S(O)2CH2, S(O)2NH, OCH2, NR4CH2, CH2CH2, CH=CH, te C≡C; pogotovo od S, S(O), S(O)2, NR4, CH2, SCH2, S(O)CH2, S(O)2CH2, S(O)2NH, CH2CH2, C≡C, OCH2, te NR4CH2, pri čemu je prvi atom tih skupina vezan na atom C lanca C-X-Ar.
4. Spoj prema patentnom zahtjevu 3, naznačeno time da X predstavlja dvovalentnu skupinu odabranu od S, S(O)2, CH2, SCH2, S(O)2CH2, S(O)2NH, CH2CH2, i C≡C, pri čemu je prvi atom tih skupina vezan na atom C lanca C-X-Ar.
5. Spoj prema bilo kojem od patentnih zahtjeva 1 do 4, naznačeno time da Ar predstavlja arilnu skupinu, kao što je fenil, koja može biti supstituirana s jednom ili više skupina odabranih od atoma halogena, (C1-C6)alkil, (C1-C6)halogenalkil, (C1-C6)halogenalkoksi, (C1-C6)halogentioalkoksi, CN, NO2, OR11, SR12, NR13R14, CO2R15, CONR16R17, SO2R18, SO2NR19R20, COR21, NR22COR23 i NR24SO2R25; ili skupinu koja je piridin.
6. Spoj prema patentnom zahtjevu 5, naznačeno time da Ar predstavlja skupinu odabranu od sljedećih skupina: [image] [image]
7. Spoj prema bilo kojem od patentnih zahtjeva 1 do 6, naznačeno time da W predstavlja skupine R5, SR5, OR5 ili NR5R6, s tim da R5 i R6 predstavljaju, neovisno jedan od drugoga, vodikov atom ili (C1-C6)alkilnu skupinu.
8. Spoj prema bilo kojem od patentnih zahtjeva 1 do 7, naznačeno time da R7 predstavlja vodikov atom, a R8 predstavlja (C3-C12)cikloalkilnu skupinu ili koja može biti supstituirana heterociklilom.
9. Spoj prema bilo kojem od patentnih zahtjeva 1 do 8, naznačeno time da R1 predstavlja jednu od sljedećih skupina: H, [image]
10. Spoj prema bilo kojem od patentnih zahtjeva 1 do 9, naznačeno time da je odabran od sljedećih spojeva: [image] [image] [image] [image] [image] [image]
11. Spoj prema bilo kojem od patentnih zahtjeva 1 do 10, za upotrebu kao lijek.
12. Spoj prema bilo kojem od patentnih zahtjeva 1 do 10, za upotrebu kao lijek namijenjen liječenju karcinoma, upalnih i neurodegenerativnih bolesti kao što je Alzheimerova bolest, posebice karcinoma.
13. Spoj prema bilo kojem od patentnih zahtjeva 1 do 10, za upotrebu kao inhibitor kinaza kao što je ALK, Abl i/ili c-Src.
14. Spoj prema bilo kojem od patentnih zahtjeva 1 do 10, za upotrebu kao lijek namijenjen liječenju bolesti povezane s kinazom kao što je ALK, Abl i/ili c-Src.
15. Farmaceutski pripravak koji sadrži najmanje jedan spoj formule (I) prema bilo kojem od patentnih zahtjeva 1 do 10, i najmanje jedan farmaceutski prihvatljiv ekscipijens.
16. Farmaceutski pripravak prema patentnom zahtjevu 15, koji dalje sadrži najmanje jedan drugi aktivni sastojak kao što je antikancerogeno sredstvo.
17. Farmaceutski pripravak koji sadrži: (i) najmanje jedan spoj formule (I) prema bilo kojem od patentnih zahtjeva 1 do 10, te (ii) najmanje jedan drugi aktivni sastojak, kao što je antikancerogeno sredstvo, kao kombinirani proizvod za istodobnu, odvojenu ili sekvencijalnu upotrebu.
18. Metoda priprave spoja formule (I) prema bilo kojem od patentnih zahtjeva 1 do 10, koja obuhvaća sljedeće sukcesivne korake: (a1) povezivanje između spoja sljedeće formule (A): [image] (A) u kojoj Y1, Y2, Y3 i Y4 jesu kao što je definirano u patentnom zahtjevu 1, te R29 predstavlja vodikov atom ili N-zaštićenu skupinu, sa spojem sljedeće formule (B): [image] (B) u kojoj R1, R2, U, V i n jesu kao što je definirano u patentnom zahtjevu 1, te R30= OH ili izlazna skupina kao što je Cl, da bi nastao spoj sljedeće formule (C): [image] (C) u kojoj Y1, Y2, Y3, Y4, R1, R2, U, V i n jesu kao što je definirano u patentnom zahtjevu 1, te R29 jest takav kao što je gore definirano, (b1) moguće uklanjanje zaštitne skupine s dušikova atoma koji nosi R29 skupinu i predstavlja N-zaštićenu skupinu da bi nastao spoj formule (I), (c1) moguća tvorba soli spoja formule (I) dobivena u prethodnom koraku da bi nastala farmaceutski prihvatljiva sol od istoga.
HRP20180524TT 2011-01-27 2018-03-29 Derivati tipa azaindazola ili diazaindazola kao lijek HRP20180524T1 (hr)

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FR1150651A FR2970967B1 (fr) 2011-01-27 2011-01-27 Derives de type azaindazole ou diazaindazole comme medicament
EP12701884.4A EP2668184B1 (en) 2011-01-27 2012-01-27 Derivatives of azaindazole or diazaindazole type as medicament
PCT/EP2012/051283 WO2012101239A1 (en) 2011-01-27 2012-01-27 Derivatives of azaindazole or diazaindazole type as medicament

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US (2) US20130172360A1 (hr)
EP (1) EP2668184B1 (hr)
JP (1) JP5931926B2 (hr)
KR (2) KR20180122028A (hr)
CN (1) CN103339129B (hr)
AR (1) AR084935A1 (hr)
AU (1) AU2012210467B2 (hr)
CA (1) CA2823824C (hr)
CY (1) CY1120088T1 (hr)
DK (1) DK2668184T3 (hr)
ES (1) ES2661695T3 (hr)
FR (1) FR2970967B1 (hr)
HK (1) HK1186737A1 (hr)
HR (1) HRP20180524T1 (hr)
HU (1) HUE037153T2 (hr)
IL (2) IL227496B (hr)
LT (1) LT2668184T (hr)
MA (1) MA34903B1 (hr)
MX (1) MX356411B (hr)
MY (1) MY180666A (hr)
PL (1) PL2668184T3 (hr)
PT (1) PT2668184T (hr)
RS (1) RS57101B1 (hr)
RU (1) RU2600976C2 (hr)
SI (1) SI2668184T1 (hr)
TN (1) TN2013000293A1 (hr)
TR (1) TR201802944T4 (hr)
TW (1) TWI546303B (hr)
UA (1) UA109698C2 (hr)
WO (1) WO2012101239A1 (hr)

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JP2014503574A (ja) 2014-02-13
MY180666A (en) 2020-12-04
CN103339129B (zh) 2015-07-29
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NZ614432A (en) 2015-03-27
IL227496A0 (en) 2013-09-30
AU2012210467A1 (en) 2013-09-12
KR20140014147A (ko) 2014-02-05
RU2013138624A (ru) 2015-03-10
US20130085144A1 (en) 2013-04-04
MX2013008673A (es) 2013-12-02
TN2013000293A1 (en) 2015-01-20
AU2012210467B2 (en) 2016-07-07
IL257748A (en) 2018-04-30
PT2668184T (pt) 2018-03-13
DK2668184T3 (en) 2018-03-12
PL2668184T3 (pl) 2018-06-29
JP5931926B2 (ja) 2016-06-08
US8883821B2 (en) 2014-11-11
CN103339129A (zh) 2013-10-02
ES2661695T3 (es) 2018-04-03
KR20180122028A (ko) 2018-11-09
LT2668184T (lt) 2018-04-10
FR2970967B1 (fr) 2013-02-15
CY1120088T1 (el) 2018-12-12
US20130172360A1 (en) 2013-07-04
EP2668184A1 (en) 2013-12-04
MX356411B (es) 2018-05-24
CA2823824A1 (en) 2012-08-02
KR101923751B1 (ko) 2018-11-29
RS57101B1 (sr) 2018-06-29
TR201802944T4 (tr) 2018-03-21
IL227496B (en) 2019-02-28
EP2668184B1 (en) 2018-01-10
HUE037153T2 (hu) 2018-08-28
CA2823824C (en) 2018-12-11
FR2970967A1 (fr) 2012-08-03
IL257748B (en) 2020-06-30
WO2012101239A1 (en) 2012-08-02
HK1186737A1 (en) 2014-03-21
SI2668184T1 (en) 2018-06-29
MA34903B1 (fr) 2014-02-01
AR084935A1 (es) 2013-07-10
TWI546303B (zh) 2016-08-21
RU2600976C2 (ru) 2016-10-27

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