HRP20210344T1 - Pripravci i postupci liječenja poremećaja cns - Google Patents

Pripravci i postupci liječenja poremećaja cns Download PDF

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HRP20210344T1
HRP20210344T1 HRP20210344TT HRP20210344T HRP20210344T1 HR P20210344 T1 HRP20210344 T1 HR P20210344T1 HR P20210344T T HRP20210344T T HR P20210344TT HR P20210344 T HRP20210344 T HR P20210344T HR P20210344 T1 HRP20210344 T1 HR P20210344T1
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image
compound
heteroaryl
alkyl
hydrogen
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Albert Jean Robichaud
Gabriel Martinez Botella
Francesco G. Salituro
Boyd L. Harrison
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Sage Therapeutics, Inc.
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    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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    • C07J—STEROIDS
    • C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
    • C07J13/007—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 17 (20)
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    • C07J3/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom
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    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0044—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 with an estrane or gonane skeleton, including 18-substituted derivatives and derivatives where position 17-beta is substituted by a carbon atom not directly bonded to another carbon atom and not being part of an amide group
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    • C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
    • C07J7/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa
    • C07J7/002—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa not substituted in position 16
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    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
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    • C07J7/0065—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by an OH group free esterified or etherified
    • C07J7/007—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by an OH group free esterified or etherified not substituted in position 17 alfa
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    • C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
    • C07J7/008—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21
    • C07J7/0085—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21 by an halogen atom
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    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
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    • C07J7/009—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21 by only one oxygen atom doubly bound
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Claims (20)

1. Spoj Formule (I): [image] , ili njegova farmaceutski prihvatljiva sol; naznačen time što: Prsten A je izborno supstituirani aril ili heteroaril; R1 je nesupstituirani C1-3 alkil; R2 je odsutan ili je vodik; R3 je vodik ili -CH2OR3A, gdje je R3A vodik, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, aril, heteroaril ili C3-6 karbociklil; ----- predstavlja jednostruku ili dvostruku vezu, gdje kada je jedan ----- dvostruka veza, drugi ----- je jednostruka veza.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je spoj Formule (I) spoj kojeg se bira između: i) spoja Formule (I-b): [image] , gdje: Prsten A je izborno supstituirani aril ili heteroaril; R1 je nesupstituirani C1-3 alkil; R2 je odsutan ili je vodik; n je 0, 1, 2, 3, 4 ili 5; Ra je halogen, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, karbociklil, heterociklil, aril, heteroaril, -C(O)RA, -C(O)ORA, -C(O)NRBRC, -S(O)2RD ili -ORY, gdje je RY vodik, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, karbociklil, heterociklil, aril, heteroaril, -C(O)RA, -C(O)ORA, -C(O)NRBRC ili -S(O)2RD; RA je vodik, C1-C6 alkil, karbociklil, heterociklil, aril ili heteroaril; svaki od RB i RC je neovisno vodik, C1-C6 alkil, karbociklil, heterociklil, aril, heteroaril, ili uzeti zajedno s atomom na kojeg su vezani tvore prsten, primjerice 3-7-eročlani prsten, primjerice, 5-7-eročlani prsten; gdje prsten sadrži najmanje jedan heteroatom, primjerice atom dušika, kisika ili sumpora; i RD je vodik, C1-C6 alkil, karbociklil, heterociklil, aril ili heteroaril; i ii) spoja Formule (I-c): [image] , gdje: Prsten A je izborno supstituirani aril ili heteroaril; R1 je nesupstituirani C1-3 alkil; R2 je odsutan ili je vodik; gdje R3A je vodik, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, aril, heteroaril ili C3-6 karbociklil; n je 0, 1, 2, 3, 4 ili 5; Ra je halogen, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, karbociklil, heterociklil, aril, heteroaril, -C(O)RA, -C(O)ORA, -C(O)NRBRC, -S(O)2RD ili -ORY, gdje RY je vodik, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, karbociklil, heterociklil, aril, heteroaril, -C(O)RA,-C(O)ORA, -C(O)NRBRC ili -S(O)2RD; RA je vodik, C1-C6 alkil, karbociklil, heterociklil, aril ili heteroaril; svaki od RB i RC je neovisno vodik, C1-C6 alkil, karbociklil, heterociklil, aril, heteroaril, ili uzeti zajedno s atomom na kojeg su vezani tvore prsten, primjerice 3-7-eročlani prsten, primjerice 5-7-eročlani prsten; gdje prsten sadrži najmanje jedan heteroatom, primjerice atom dušika, kisika ili sumpora; i RD je vodik, C1-C6 alkil, karbociklil, heterociklil, aril ili heteroaril.
3. Spoj u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2, naznačen time što je A 5-7-eročlani prsten, primjerice gdje je A monociklički ili biciklički.
4. Spoj u skladu s patentnim zahtjevom 3, naznačen time što je A monociklički ili biciklički i sadrži najmanje jedan atom dušika ili dva atoma dušika.
5. Spoj u skladu s patentnim zahtjevom 3, naznačen time što: i) A je 5-eročlani prsten, primjerice gdje je A oksazol, pirazol ili tiazol; ili ii) A je 6-eročlani prsten, primjerice gdje se A bira između arilnog prstena, primjerice fenila, i heteroarilnog prstena, primjerice piridina ili pirimidina.
6. Spoj u skladu s patentnim zahtjevom 2, naznačen time što je n 0 ili 1, ili što je n 1, a Ra je alkil.
7. Spoj u skladu s patentnim zahtjevom 2, naznačen time što ga se bira između: i) spoja Formule (I-b), kojeg se bira između spojeva Formule (I-b-i), (I-b-ii), (I-b-iii), te (I-b-iv): [image] , [image] , [image] , te [image] ; ii) spoja Formule (I-b), kojeg se bira između: [image] , [image] , [image] , [image] , [image] , [image] , [image] ili [image] .
8. Spoj u skladu s patentnim zahtjevom 2, naznačen time što ga se bira između: i) spoja Formule (I-c), kojeg se bira između spojeva Formule (I-c-i), (I-c-ii), (I-c-iii) ili (I-c-iv): [image] , [image] , [image] , te [image] ; ii) spoja Formule (I-c), kojeg se bira između: [image] , [image] , [image] , [image] , [image] , [image] , [image] , te [image] .
9. Farmaceutski pripravak, naznačen time što sadrži spoj u skladu s bilo kojim od prethodnih patentnih zahtjeva, kao i farmaceutski prihvatljivo pomoćno sredstvo.
10. Spoj Formule (I): [image] , ili njegova farmaceutski prihvatljiva sol; gdje: Prsten A je izborno supstituirani aril ili heteroaril; R1 je nesupstituirani C1-3 alkil; R2 je odsutan ili je vodik; R3 je vodik ili -CH2OR3A, gdje je R3A vodik, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, aril, heteroaril ili C3-6 karbociklil; ----- predstavlja jednostruku ili dvostruku vezu, gdje kada je jedan ----- dvostruka veza, drugi ----- je jednostruka veza; namijenjen upotrebi u postupku kojeg se bira između: i) postupka izazivanja smirivanja i/ili anestezije kod subjekta; ii) postupka liječenja konvulzije kod subjekta; iii) postupka liječenja epilepsije kod subjekta; iv) postupka liječenja epileptičnog statusa (SE) kod subjekta kojem je to potrebno, primjerice gdje je epileptični status konvulzivni epileptični status; primjerice rani epileptični status, etabilirani epileptični status, refrakterni epileptični status, superrefrakterni epileptični status; ili nonkonvulzivni epileptični status, primjerice generalizirani epileptični status, kompleksni parcijalni epileptični status; v) postupka liječenja poremećaja povezanog s funkcijom GABA; kod subjekta kojem je to potrebno; vi) postupka liječenja poremećaja povezanog s CNS-om kod subjekta kojem je to potrebno, primjerice gdje je poremećaj povezan s CNS-om poremećaj spavanja, poremećaj raspoloženja; primjerice depresija, primjerice poslijeporođajna depresija; spektar shizofrenih poremećaja, konvulzivni poremećaj, poremećaj pamćenja i/ili spoznaje, poremećaj kretanja; primjerice drhtavica, primjerice esencijalna drhtavica; anksiozni poremećaj, poremećaj ličnosti, spektar autističnih poremećaja, bol, traumatska ozljeda mozga, vaskularna bolest, poremećaj zloupotrebe tvari i/ili sindrom ustezanja, ili tinitus; vii) postupka liječenja ljudskog subjekta koji boluje od depresije; primjerice poslijeporođajne depresije ili teške poslijeporođajne depresije; viii) postupka liječenja ljudskog subjekta koji boluje od drhtavice, primjerice esencijalne drhtavice, naznačen time što se postupak sastoji u primjeni djelotvorne količine spoja Formule (I).
11. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 10, naznačen time što je postupak postupak izazivanja smirivanja i/ili anestezije, te što subjekt osjeća smirivanje i/ili anesteziju unutar dva sata nakon primjene, ili što subjekt osjeća smirivanje i/ili anesteziju unutar jednog sata nakon primjene, ili što subjekt odmah osjeća smirivanje i/ili anesteziju.
12. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 10, naznačen time što je postupak postupak izazivanja smirivanja i/ili anestezije, te što se spoj primjenjuje intravenskom primjenom, ili što se spoj primjenjuje kronično.
13. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 10, naznačen time što je postupak postupak izazivanja smirivanja i/ili anestezije, te što je subjekt sisavac, primjerice čovjek.
14. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 10, naznačen time što je postupak postupak izazivanja smirivanja i/ili anestezije, te što se spoj primjenjuje u kombinaciju s drugim terapijskim sredstvom.
15. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 10, naznačen time što je postupak postupak liječenja poremećaja povezanog s CNS-om, te što se spoj primjenjuje oralno ili intramuskularno.
16. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 10, naznačen time što je postupak postupak liječenja poremećaja povezanog s CNS-om, te što je subjekt subjekt s Rettovim sindromom, sindromom lomljivog kromosoma X ili Angelmanovim sindromom.
17. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 10, naznačen time što je postupak postupak liječenja ljudskog subjekta koji boluje od depresije, ili postupak liječenja ljudskog subjekta koji boluje od drhtavice, te što se primjenu provodi oralno, parenteralno ili intravenski, primjerice kontinuiranom intravenskom infuzijom.
18. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 10, naznačen time što je postupak postupak liječenja depresije, te što je subjekt ženska osoba i/ili odrasla osoba, primjerice stara 18 do 45 godina.
19. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 18, naznačen time što je subjekt prošao veliku depresivnu epizodu u poslijeporođajnom periodu, primjerice gdje period počinje unutar prva 4 tjedna nakon rađanja bebe.
20. Komplet, naznačen time što sadrži čvrsti pripravak, koji sadrži spoj Formule (I): [image] , ili njegovu farmaceutski prihvatljivu sol; gdje: Prsten A je izborno supstituirani aril ili heteroaril; R1 je nesupstituirani C1-3 alkil; R2 je odsutan ili je vodik; R3 je vodik ili -CH2OR3A, gdje je R3A vodik, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, aril, heteroaril ili C3-6 karbociklil; ----- predstavlja jednostruku ili dvostruku vezu, gdje kada je jedan ----- dvostruka veza, drugi ----- je jednostruka veza.
HRP20210344TT 2015-01-26 2021-03-01 Pripravci i postupci liječenja poremećaja cns HRP20210344T1 (hr)

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Application Number Priority Date Filing Date Title
US201562107776P 2015-01-26 2015-01-26
US201562144789P 2015-04-08 2015-04-08
EP16743932.2A EP3250210B1 (en) 2015-01-26 2016-01-26 Compositions and methods for treating cns disorders
PCT/US2016/014835 WO2016123056A1 (en) 2015-01-26 2016-01-26 Compositions and methods for treating cns disorders

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US20200246459A1 (en) 2020-08-06
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