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ME02635B - Novi derivati pirola, postupak njihove priprave i farmaceutski pripravci koji ih sadrže - Google Patents

Novi derivati pirola, postupak njihove priprave i farmaceutski pripravci koji ih sadrže

Info

Publication number
ME02635B
ME02635B MEP-2017-63A MEP201763A ME02635B ME 02635 B ME02635 B ME 02635B ME P201763 A MEP201763 A ME P201763A ME 02635 B ME02635 B ME 02635B
Authority
ME
Montenegro
Prior art keywords
formula
compound
dimethyl
morpholin
hydroxyphenyl
Prior art date
Application number
MEP-2017-63A
Other languages
German (de)
English (en)
French (fr)
Inventor
Tiran Arnaud Le
Diguarher Thierry Le
Jérôme-Benoît Starck
Jean-Michel Henlin
Anne-Françoise Guillouzic
Nanteuil Guillaume De
Olivier Geneste
Imre Fejes
Janos Tatai
Miklos Nyerges
James Edward Paul Davidson
James Brooke Murray
I-Jen Chen
Didier Durand
Original Assignee
Servier Lab
Vernalis R&D Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=50023639&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ME02635(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Servier Lab, Vernalis R&D Ltd filed Critical Servier Lab
Publication of ME02635B publication Critical patent/ME02635B/me

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    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
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    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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    • A61K31/5375—1,4-Oxazines, e.g. morpholine
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    • C07D401/02—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
    • C07D401/10—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 carbon chain containing aromatic rings
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    • C07D401/02—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
    • 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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    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
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    • C07D498/14—Ortho-condensed systems

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  • Nitrogen Condensed Heterocyclic Rings (AREA)
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Claims (35)

1. Spoj formule (I): naznačen time, da: ♦ A1 predstavlja atom vodika ili halogena, ravnu ili razgrananu (C1-C6)polihaloalkilnu skupinu, ravnu ili razgrananu (C1-C6)alkilnu skupinu ili cikloalkilnu skupinu, ♦ A2 predstavlja ravnu ili razgrananu (C1-C6)alkilnu skupinu po izboru supstituiranu sa skupinom odabranom od halogena, hidroksi, ravnog ili razgrananog (C1-C6)alkoksi, NR'R'' i morfolina ili A2 predstavlja ravnu ili razgrananu (C1-C6)polihaloalkilnu skupinu ili ciklopropilnu skupinu, gdje se podrazumijeva da R' i R", svaki neovisno jedan o drugome, predstavljanju atom vodika ili ravnu ili razgrananu (C1-C6)alkilnu skupinu, ♦ T predstavlja atom vodika, ravnu ili razgrananu (C1-C6)alkilnu skupinu po izboru supstituiranu s jednim do tri atoma halogena, skupinu (C1-C4)alkil-NR1R2 ili skupinu (C1-C4)alkil-OR6, ♦ R1 i R2, svaki neovisno jedan o drugome, predstavljaju atom vodika ili ravnu ili razgrananu (C1-C6)alkilnu skupinu ili R1 i R2 tvore s dušikovim atomom koji ih nosi heterocikloalkil, ♦ R3 predstavlja arilnu ili heteroarilnu skupinu, pri čemu se podrazumijeva da jedan ili više ugljikovih atoma iz prethodnih skupina ili njihovi mogući supstituenti mogu biti deuterirani, ♦ R4 predstavlja fenilnu skupinu, 4-hidroksifenilnu skupinu, 3-fluoro-4-hidroksifenilnu skupinu, 2-hidroksipirimidinsku skupinu ili 3-hidroksipiridinsku skupinu, pri čemu se podrazumijeva da jedan ili više ugljikovih atoma iz prethodnih skupina ili njihovi mogući supstituenti mogu biti deuterirani, ♦ R5 predstavlja atom vodika ili atom halogena, ravnu ili razgrananu (C1-C6)alkilnu skupinu ili ravnu ili razgrananu (C1-C6)alkoksi skupinu, ♦ R6 predstavlja atom vodika ili ravnu ili razgrananu (C1-C6)alkilnu skupinu, ♦ Ra i Rd svaki predstavlja atom vodika i (Rb,Rc) zajedno s ugljikovim atomom koji ih nose tvore skupinu 1,3-dioksolana ili skupinu 1,4-dioksana ili Ra, Rc and Rd svaki predstavlja atom vodika i Rb predstavlja atom vodika ili halogena ili metoksi skupinu ili Ra i Rd svaki predstavlja atom vodika, Rb predstavlja atom vodika ili atom halogena i Rc predstavlja hidroski ili metoksi skupinu ili: Ra i Rd svaki predstavlja atom vodika, Rb predstavlja hidroksi ili metoksi skupinu i Rc predstavlja atom halogena, gdje se podrazumijeva kako: - "aril" znači fenilna, naftilna, bifenilna ili indenilna skupina, - "heteroaril" znači bilo koja mono- ili bi-ciklička skupina sastavljena od 5 do 10 članova prstena, koja ima najmanje jednu aromatsku polovicu i sastoji se od 1 do 4 heteroatoma odabrana od kisika, sumpora i dušika (uključujući kvaterne dušike), - "cikloalkil” znači bilo koja mono- ili bi-ciklička, ne-aromatska, karbociklička skupina koja se sastoji od 3 do 10 članova prstena, - "heterocikloalkil" znači bilo koja mono- ili bi-ciklička, ne-aromatska, kondenzirana ili spiro skupina koja se sastoji od 3 do 10 članova prstena i sadrži od 1 do 3 heteroatoma odabrana od kisika, sumpora, SO, SO2 i dušika, pri čemu je moguće za tako definirane arilne, heteroarilne, cikloalkilne i heterocikloalkilne skupine i skupine alkila, alkenil, alkinila i alkoksi da budu supstituirane s 1 do 3 skupine odabrane od ravnog ili razgrananog (C1-C6)alkila, (C3-C6)spiro, ravnog ili razgrananog (C1-C6)alkoksi, (C1-C6)alkil-S-, hidroksi, okso (ili N-oksida gdje je prikladno), nitro, cijano, -COOR', -OCOR', NR'R'', ravnog ili razgrananog (C1-C6)polihaloalkila, trifluorometoksi, (C1-C6)alkilsulfonila, halogena, arila, heteroarila, ariloksi, ariltio, cikloalkila, heterocikloalkila po izboru supstituiranog s jednim ili više atoma halogena ili alkilnim skupinama, njegove enantiomere i dijastereoizomere i njihove adicijske soli s s farmaceutski prihvatljivom kiselinom ili lužinom.
2. Spoj formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da A1 predstavlja atom vodika ili metilnu skupinu.
3. Spoj formule (I) u skladu s patentnim zahtjevom 1 ili 2, naznačen time, da A1 i A2 oba predstavljaju metilnu skupinu.
4. Spoj formule (I) u skladu s jednim od patentnih zahtjeva 1 do 3, naznačen time, da T predstavlja metil, aminometil, (morfolin-4-il)metil, (4-metilpiperazin-1-il)metil, 2-(morfolin-4-il)etil, [2-(morfolin-4-il)etoksi]metil, hidroksimetil,[2-(dimetilamino)etoksi]metil, heksahidropirazino[2,1-c][1,4]oksazin-8(1H)-ilmetil, 1-oksa-6-azaspiro[3.3]hept-6-ilmetil, 3-(morfolin-4-il)propilnu ili trifluorometilnu skupinu.
5. Spoj formule (I): u skladu s patentnim zahtjevom 1, naznačen time, da - A1, A2, Ra, Rb, Rc, Rd, T, R4 i R5 jesu definirani u patentnim zahtjevima 1 do 4, - R3 predstavlja skupinu odabranu od fenila, 1H-pirazola, 1H-indola, 1H-indazola, piridina, pirimidina, 1H-pirolo[ 2,3-b]piridina, 2,3-dihidro-1H-pirolo[2,3-b]piridina, 1H-benzimidazola, 1H-pirola, 1H-pirolo[2,3- c]piridina, 1H-pirolo[3,2-b]piridina, 5H-pirolo[3,2-d]pirimidina, tiofena, pirazina, 1H-pirazolo[3,4-b]piridina, 1,2-oksazola i pirazolo[1,5-a]pirimidina, te skupine po izboru imaju jednog ili više supstituenata odabrana od halogena, ravnog ili razgrananog (C1-C6)alkila, ravnog ili razgrananog (C1-C6)alkoksi, cijano, ciklopropila, oksetana, tetrahidrofurana, -CO-O-CH3, trideuteriometila, 2-(morfolin-4-il)etila i 2-(morfolin-4-il)etoksi, njihovih enantiomera i dijastereoizomera te njihovih adicijskih soli s farmaceutski prihvatljivom kiselinom ili lužinom.
6. Spoj formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da je odabran iz sljedeće skupine: - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirazol-4-il)-1H-pirol-3-karboksamid, - 5-(5-kloro-2-{[(3R)-3-metil-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2- dimetil-N-(piridin-4-il)-1H-pirol-3-karboksamida, - N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirazol-4-il)-5-(6-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}-1,3-benzoadioksol-5-il)-1H-pirol-3-karboksamida, - N-(4-hidroksifenil)-1,2-dimetil-5-(6-{[(3R)-3-metil-3,4-dihidroizokinolin-2(1H)-il]karbonil}-1,3-benzodioksol-5-il)-N-(piridin-4-il)-1H-pirol-3-karboksamida, - 5-(5-fluoro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirazol-4-il)-1H-pirol-3-karboksamida, - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirolo[2,3-b]piridin-5-il)-1H-pirol-3-karboksamida, - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(piridin-4-il)-1H-pirol-3-karboksamida, - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(5-cijano- 1-metil-1H-pirol-3-il)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamida, - N-(5-cijano-1-metil-1H-pirol-3-il)-5-(5-fluoro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin- 2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamida, - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(5-cijano- 1,2-dimetil-1H-pirol-3-il)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamida, - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-2,3-dihidro-1H-pirolo[2,3-b]piridin-5-il)-1H-pirol-3-karboksamida, - N-(5-cijano-1,2-dimetil-1H-pirol-3-il)-5-(5-fluoro-2-{[(3S)-3-(morfolin-4-il-metil)-3,4 dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamida, - 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]-karbonil}fenil)-N-[5-cijano-2-metil-1-(trideuteriometil)-1H-pirol-3-il]-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamida, njihovih enantiomera i dijastereoizomera te njihovih adicijskih soli s farmaceutski prihvatljivom kiselinom ili lužinom.
7. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirazol-4-il)-1H-pirol-3-karboksamid.
8. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3R)-3-metil-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(piridin-4-il)-1H-pirol-3-karboksamid.
9. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirazol-4-il)-5-(6-[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}-1,3-benzodioksol-5-il)-1H-pirol-3-karboksamid.
10. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je N-(4-hidroksifenil)-1,2-dimetil-5-(6-{[(3R)-3-metil-3,4-dihidroizokinolin-2(1H)-il]karbonil}-1,3-benzodioksol-5-il)-N-(piridin-4-il)-1H-pirol-3 karboksamid.
11. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-fluoro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirazol-4-il)-1H-pirol-3-karboksamid.
12. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-1H-pirolo[2,3-b]piridin-5-il)-1H-pirol-3-karboksamid.
13. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(piridin-4-il)-1H-pirol-3-karboksamid.
14. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(5-cijano-1-metil-1H-pirol-3-il)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamid.
15. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je N-(5-cijano-1-metil-1H-pirol-3-il)-5-(5-fluoro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamid.
16. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(5-cijano-1,2-dimetil-1H-pirol-3-il)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamid.
17. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-N-(1-metil-2,3-dihidro-1H-pirolo[2,3-b]piridin-5-il)-1H-pirol-3-karboksamid.
18. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je N-(5-cijano-1,2-dimetil-1H-pirol-3-il)-5-(5-fluoro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamid.
19. Spoj formule (I) u skladu s patentnim zahtjevom 6, naznačen time, da je 5-(5-kloro-2-{[(3S)-3-(morfolin-4-ilmetil)-3,4-dihidroizokinolin-2(1H)-il]karbonil}fenil)-N-[5-cijano-2-metil-1-(trideuteriometil)-1H-pirol-3-il]-N-(4-hidroksifenil)-1,2-dimetil-1H-pirol-3-karboksamid.
20. Postupak za pripravu spojeva formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da je kao početni materijal korišten spoj formule (II): pri čemu su Ra, Rb, Rc i Rd kako je definirano za formulu (I), koji spoj formule (II) je izložen Heckovoj reakciji u vodenom ili organskom mediju u nazočnosti paladijevog katalizatora, lužine, fosfina i spoja formule (III): gdje su skupine A1 i A2 kako je definirano za formulu (I) i Alk predstavlja ravni ili razgranani (C1-C6)alkil, kako bi se dobio spoj formule (IV): pri čemu su A1, A2, Ra, Rb, Rc i Rd definirani za formulu (I) i Alk je ranije gore definiran, funkcija aldehida kojim je spoj formule (IV) oksidiran u karboksilnu kiselinu kako bi se dobio spoj formule (V): pri čemu su A1, A2, Ra, Rb, Rc i Rd defininirani za formulu (I) i Alk je ranije gore definiran, koji se spoj formule (V) potom izlaže spajanju peptida sa spojem formule (VI): pri čemu su T i R5 definirani za formulu (I), kako bi se dobio spoj formule (VII): pri čemu su A1, A2, Ra, Rb, Rc i Rd, T i R5 definirano za formulu (I) i Alk je ranije gore definiran, esterska funkcija kojom je hidraliziran spoj formule (VII) kako bi se dobila odgovarajuća karboksilna kiselina ili karboksilat, koji se može pretvoriti u derivat kiseline poput primjerice u acil-klorida ili anhidrid prije spajanja s NHR3R4 aminom, gdje R3 i R4 imaju ista značenja kao za formulu (I), kako bi se dobio spoj formule (I), koji se spoj formule (I) može pročišćavati u skladu s uobičajenim tehnikama separacije, koji se može pretvoriti, ako je poželjno, u svoje adicijske soli s farmaceutski prihvatljivom kiselinom ili lužinom i koji je po izboru razdvojen u svoje izomere u skladu s uobičajenim tehnikama separacije, gdje se podrazumijeva, da se bilo koje vrijeme smatra prikladnim u smislu gore opisanog postupka, izvjesne skupine (hidroksi, amino...) reagensa ili intermedijera sinteze mogu biti zaštićene a potom im se skida zaštita u skladu sa zahtjevima sinteze.
21. Postupak u skladu s patentnim zahtjevom 20 za pripravu spoja formule (I) gdje je jedna od skupina R3 ili R4 supstituirana s hidroksi funkcijom, naznačen time, da je amin NHR3R4 prije toga izložen reakciji štiteći hidroksi funkciju prije bilo kakvog spajanja s karboksilnom kiselinom dobivenom od spoja formule (VII) ili s odgovarajućim derivatom kiseline, dobiveni zaštićeni spoj formule (I) naknadno se podvrgava reakciji skidanja zaštite a potom se po izboru pretvara u jednu od njegovih adicijskih soli s farmaceutski prihvatljivom kiselinom ili lužinom.
22. Farmaceutski pripravak koji sadrži spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 19 ili njegove adicijske soli s farmaceutski prihvatljivom kiselinom ili lužinom, naznačen time, da je u kombinaciji s jednim ili više farmaceutski prihvatljivih ekscipijensa.
23. Farmaceutski pripravak u skladu s patentnim zahtjevom 22, naznačen time, da je za uporabu kao pro-apoptotičko sredstvo.
24. Farmaceutski pripravak u skladu s patentnim zahtjevom 22, naznačen time, da je za uporabu u liječenju karcinoma, autoimunih bolesti i bolesti imunog sustava.
25. Farmaceutski pripravak u skladu s patentnim zahtjevom 22, naznačen time, da je za uporabu u liječenju raka mjehura, mozga, dojki i maternice, kronične limfoidne leukemije, raka debelog crijeva, raka jednjaka i jetre, leukemije limfoblasta, ne-Hodgkinovog limfoma, melanoma, maligne hemopatije, mijeloma, raka jajnika, raka pluća ne-malih stanica, raka prostate i raka pluća malih stanica.
26. Uporaba farmaceutskog pripravka u skladu s patentnim zahtjevom 22, naznačena time, da je za proizvodnju lijeka za uporabu kao apoptotičkog sredstva.
27. Uporaba farmaceutskog pripravka u skladu s patentnim zahtjevom 22, naznačena time, da je za proizvodnju lijeka za liječenje karcinoma, bolesti imunog sustava i auto-imunih bolesti.
28. Uporaba farmaceutskog pripravka u skladu s patentnim zahtjevom 22, naznačena time, da je za proizvodnju lijeka namijenjenog za liječenje raka mjehura, mozga, dojki i maternice, kronične limfoidne leukemije, raka debelog crijeva, raka jednjaka i jetre, leukemije limfoblasta, ne-Hodgkinovog limfoma, melanoma, maligne hemopatije, mijeloma, raka jajnika, raka pluća ne-malih stanica, raka prostate i raka pluća malih stanica.
29. Spoj formule (I) u skladu s jednim od patentnih zahtjeva 1 do 19, ili njegova adicijska sol s farmaceutksi prihvatljivom kiselinom ili lužinom, naznačen time, da se koristi u liječenju raka mjehura, mozga, dojki i maternice, kronične limfoidne leukemije, raka debelog crijeva, raka jednjaka i jetre, leukemije limfoblasta, ne-Hodgkinovog limfoma, melanoma, maligne hemopatije, mijeloma, raka jajnika, raka pluća ne-malih stanica, raka prostate i raka pluća malih stanica.
30. Uporaba spoja formule (I) u skladu s jednim od patentnih zahtjeva 1 do 19, ili njegova adicijska sol s farmaceutksi prihvatljivom kiselinom ili lužinom, naznačen time, da je za proizvodnju lijeka namijenjenog za liječenje raka mjehura, mozga, dojki i maternice, kronične limfoidne leukemije, raka debelog crijeva, raka jednjaka i jetre, leukemije limfoblasta, ne-Hodgkinovog limfoma, melanoma, maligne hemopatije, mijeloma, raka jajnika, raka pluća ne-malih stanica, raka prostate i raka pluća malih stanica.
31. Kombinacija spoja formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 19, naznačen time, da se kombinira s protutumorskim sredstvom koje je odabrano od genotoksičnih sredstava, mitotičkih otrova, antimetabolita, inhibitora proteazoma, inhibitora kinaze i protutijela.
32. Farmaceutski pripravak koji sadrži kombinaciju u skladu s patentnim zahtjevom 31, naznačen time, da se kombinira s jednim ili više farmaceutski prihvatljivih ekscipijensa.
33. Kombinacija u skladu s patentnim zahtjevom 31, naznačeno time, da je za uporabu u liječenju karcinoma.
34. Uporaba kombinacije u skladu s patentnim zahtjevom 31, naznačena time, da je za proizvodnju lijeka za uporabu u liječenju karcinoma.
35. Spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 19, naznačen time, da je za uporabu u kombinaciji s radioterapijom za liječenje karcinoma.
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Families Citing this family (31)

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Publication number Priority date Publication date Assignee Title
FR3008975A1 (fr) * 2013-07-23 2015-01-30 Servier Lab Nouveaux derives de pyrrole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO2018015526A1 (en) 2016-07-22 2018-01-25 Les Laboratoires Servier Combination of a bcl-2 inhibitor and a mcl-1 inhibitor, uses and pharmaceutical compositions thereof
UA125138C2 (uk) * 2016-07-22 2022-01-19 Ле Лаборатуар Сервьє Комбінація інгібітора bcl-2 та інгібітора mcl-1, їхнє застосування і фармацевтичні композиції
WO2018158225A1 (en) 2017-02-28 2018-09-07 Les Laboratoires Servier Combination of a bcl-2 inhibitor and a mdm2 inhibitor, uses and pharmaceutical compositions thereof
FR3072679B1 (fr) * 2017-10-25 2020-10-30 Servier Lab Nouveaux derives macrocycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO2019236884A1 (en) 2018-06-07 2019-12-12 Disarm Therapeutics, Inc. Inhibitors of sarm1
UY38431A (es) * 2018-10-31 2020-05-29 Servier Lab Formulación basada en ciclodextrina de un inhibidor de bcl-2
GEP20237494B (en) * 2018-10-31 2023-04-10 Servier Lab Novel salt of a bcl-2 inhibitor, related crystalline form, method for preparing the same and pharmaceutical compositions containing the same
US12129261B2 (en) * 2018-12-06 2024-10-29 Les Laboratoires Servier Crystalline forms of a MCL-1 inhibitor, a process for their preparation and pharmaceutical compositions containing them
CA3123215C (en) 2018-12-19 2024-04-02 Disarm Therapeutics, Inc. Inhibitors of sarm1 in combination with neuroprotective agents
KR102468480B1 (ko) 2018-12-27 2022-11-18 홀로스메딕 주식회사 신규한 화합물 및 이를 포함하는 항암 활성 증진용 약학 조성물
WO2020139044A1 (ko) * 2018-12-27 2020-07-02 홀로스메딕 주식회사 신규한 화합물 및 이를 포함하는 항암 활성 증진용 약학 조성물
MD3969000T2 (ro) * 2019-05-14 2023-12-31 Servier Lab Inhibitori de Bcl-2 pentru utilizare în tratamentul unui cancer mediat de Bcl-2 care poartă mutația Gly101Val
US20230092679A1 (en) 2019-05-20 2023-03-23 Novartis Ag Mcl-1 inhibitor antibody-drug conjugates and methods of use
KR20230044452A (ko) 2020-07-31 2023-04-04 르 라보레또레 쎄르비에르 암을 치료하기 위한 bcl-2 억제제 및 저메틸화제의 조합물, 이의 용도 및 약학적 조성물
WO2022090443A1 (en) 2020-10-30 2022-05-05 Les Laboratoires Servier Administration and dose regimen for a combination of a bcl-2 inhibitor and a mcl1 inhibitor
US20240042051A1 (en) 2020-11-24 2024-02-08 Francesca Rocchetti Mcl-1 inhibitor antibody-drug conjugates and methods of use
CN117794929A (zh) 2021-02-02 2024-03-29 法国施维雅药厂 选择性bcl-xl protac化合物及使用方法
CN113129644B (zh) * 2021-03-05 2022-03-08 中国人民解放军国防科技大学 基于球面扫描线的船舶三维特征航线提取方法
CN116997544A (zh) * 2021-03-24 2023-11-03 法国施维雅药厂 用于合成5-{5-氯-2-[(3s)-3-[(吗啉-4-基)甲基]-3,4-二氢异喹啉-2(1h)-羰基]苯基}-1,2-二甲基-1h-吡咯-3-甲酸衍生物的新方法及其在生产药物化合物中的应用
EP4332091A4 (en) * 2021-04-26 2025-06-18 Sunshine Lake Pharma Co., Ltd. METHOD FOR PREPARING A PYRROLAMIDE COMPOUND
CA3240077A1 (en) * 2021-12-29 2023-07-06 Volodymyr KYSIL Bcl-2 inhibitors
CN114736156B (zh) * 2022-05-18 2024-03-19 中捷四方生物科技股份有限公司 一种白叶藤碱简化衍生物的制备方法及用途
WO2023225359A1 (en) 2022-05-20 2023-11-23 Novartis Ag Antibody-drug conjugates of antineoplastic compounds and methods of use thereof
KR20250027281A (ko) 2022-05-20 2025-02-25 노파르티스 아게 Epha2 bcl-xl 억제제 항체-약물 접합체 및 그의 사용 방법
AU2023273734A1 (en) 2022-05-20 2024-12-12 Les Laboratoires Servier Met bcl-xl inhibitor antibody-drug conjugates and methods of use thereof
CN115960121B (zh) * 2022-10-27 2025-09-12 南通药明康德医药科技有限公司 一种合成1-(3-氧杂丁环烷基)-1h-吡唑-4-硼酸频哪醇酯的方法
IL322700A (en) 2023-03-10 2025-10-01 Novartis Ag Antibody-drug conjugates that inhibit fennerase and methods of using them
WO2025111450A1 (en) 2023-11-22 2025-05-30 Les Laboratoires Servier Anti-cd74 antibody-drug conjugates and methods of use thereof
WO2025111431A1 (en) * 2023-11-22 2025-05-30 Les Laboratoires Servier Anti-cd7 antibody-drug conjugates and methods of use thereof
WO2025215536A1 (en) 2024-04-10 2025-10-16 Novartis Ag Macrocyclic panras inhibitors for the treatment of cancer

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE216388T1 (de) 1995-12-01 2002-05-15 Suntory Ltd Pyrroloazepin-derivate
US7122544B2 (en) 2000-12-06 2006-10-17 Signal Pharmaceuticals, Llc Anilinopyrimidine derivatives as IKK inhibitors and compositions and methods related thereto
AU2005277223C1 (en) * 2004-08-20 2009-05-21 The Regents Of The University Of Michigan Small molecule inhibitors of anti-apoptotic Bcl-2 family members and the uses thereof
US7511056B2 (en) 2004-11-10 2009-03-31 Eli Lilly And Company TGF-β inhibitors
WO2006087309A1 (en) 2005-02-15 2006-08-24 Novo Nordisk A/S 3,4-dihydro-1h-isoquinoline-2-carboxylic acid 5-aminopyridin-2-yl esters
CN101171247A (zh) * 2005-03-04 2008-04-30 阿斯利康(瑞典)有限公司 作为dna促旋酶和拓扑异构酶抑制剂的吡咯衍生物
SE531110C2 (sv) 2006-07-14 2008-12-23 Vaelinge Innovation Ab Låssystem omfattande ett kombinationslås för paneler
RU2009105196A (ru) 2006-07-14 2010-08-27 СмитКлайн Бичэм Конэрейшн (US) Противовирусные соединения (варианты), фармацевтическая композиция на их основе, названные соединения для изготовления лекарственного средства, способ лечения или профилактики вирусной инфекции с их помощью
US7706888B2 (en) 2006-07-14 2010-04-27 Med-El Elektromedizinische Geraete Gmbh Bi-planar electrode with shunting gates
JP2011518109A (ja) 2007-11-30 2011-06-23 ビオタ サイエンティフィック マネージメント ピーティーワイ リミテッド 抗菌剤としてのテトラヒドロ−イソキノリンｐｐａｔ阻害剤
WO2010080503A1 (en) 2008-12-19 2010-07-15 Genentech, Inc. Heterocyclic compounds and methods of use
US8557612B2 (en) 2009-06-26 2013-10-15 California Institute Of Technology Method for fabricating micro and nanostructures in a material
WO2012162365A1 (en) * 2011-05-25 2012-11-29 Bristol-Myers Squibb Company Substituted sulfonamides useful as antiapoptotic bcl inhibitors
JP2015503519A (ja) 2011-12-23 2015-02-02 ノバルティス アーゲー Ｂｃｌ２と結合相手の相互作用を阻害するための化合物
KR20140107575A (ko) * 2011-12-23 2014-09-04 노파르티스 아게 Bcl2와 결합 파트너의 상호작용을 억제하기 위한 화합물
FR2986002B1 (fr) * 2012-01-24 2014-02-21 Servier Lab Nouveaux derives d'indolizine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR3008975A1 (fr) * 2013-07-23 2015-01-30 Servier Lab Nouveaux derives de pyrrole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

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