HRP20120346T1 - Derivati kinolinona kao parp i tank inhibitori - Google Patents

Derivati kinolinona kao parp i tank inhibitori Download PDF

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HRP20120346T1
HRP20120346T1 HRP20120346AT HRP20120346T HRP20120346T1 HR P20120346 T1 HRP20120346 T1 HR P20120346T1 HR P20120346A T HRP20120346A T HR P20120346AT HR P20120346 T HRP20120346 T HR P20120346T HR P20120346 T1 HRP20120346 T1 HR P20120346T1
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6alkyl
formula
hydrogen
methyl
6alkynyl
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HRP20120346AT
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Eduardo Vialard Jorge
Ren� Angibaud Patrick
Anne Mevellec Laurence
Meyer Christophe
Jean Edgard Freyne Eddy
No�lle Constance Pilatte Isabelle
Roux Bruno
Th�rese Jeanne Pasquier Elisabeth
Marc Bourdrez Xavier
Denis Adelinet Christophe
Fran�oise Bernadette Marconnet-Decrane Laurence
Anne Macritchie Jacqueline
Edward Stewart Duffy James
Pate Owens Andrew
Storck Pierre-Henri
Sophie Poncelet Virginie
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Janssen Pharmaceutica N.V.
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Abstract

Spoj formule (I), njegovi N-oksidni oblici, farmaceutski prihvatljive adicijske soli i stereokemijski izomerni oblici, naznačen time dam je 0, 1 ili 2 i kada m je 0 tada je namjeravana direktna veza; n je 0, 1, 2, 3 ili 4 i kada n je 0 tada je namjeravana direktna veza; X je direktna veza, CR10R11, (C=O)NR8, NR8, O ili C?C; R1 je aril ili Het; pri čemu aril je fenil ili naftalenil; pri čemu Het je tienil, pirolil, pirolinil, oksazolil, tiazolil, imidazolil, pirazolil, izoksazolil, izotiazolil, oksadiazolil, triazolil, tetrazolil, tiadiazolil, furanil, piperidinil, piridinil, piridazinil, pirimidinil, piperazinil, pirazinil, triazinil, indolizinil, azaindolizinil, indolil, indolinil, benzotienil, indazolil, benzoksazolil, benzimidazolil, benzofuranil, benzotiazolil, benzotriazolil, kromanil, purinil, kinolinil, cinolinil, ftalazinil, kinazolinil, kinoksazolinil, naftiridinil ili pteridinil; dva atoma ugljika na arilu ili Het mogu biti premoštena (tj. formiraju bi- ili triciklički dio) sa dvovalentnim radikalom odabranim od????????-O-CH2-CH2-O- (a-1), ????????-CH2-O-CH2-O- (a-2), ????????-O-CH2-CH2- CH2- (a-3), ????????-O-CH2-CH2-NR8- (a-4), ????????-O-CR82-O- (a-5), ????????-O-CH2-CH2- (a-6), ????????-CH2-N-CH2-CH2- (a-7), ????????-(CH2)3- (a-8), ili????????-(CH2)4- (a-9); svaki aril, Het, premošteni aril ili premošteni Het može biti supstituiran sa jednim, dva, tri, četiri ili pet supstituenata koji su svaki nezavisno odabrani od vodika, halo, cijano, nitro, hidroksikarbonila, C1-6alkila, C2-6alkenila, C2-6alkinila, C3-6cikloalkila, aminoC3-6cikloalkila, haloC1-6alkila, trihaloC1-6alkila, C1-6alkilkarbonila, C1-6alkiloksikarbonila, C2-6alkenilkarbonila, oksima, C1-6alkiloksima, amidoksima, -C?C-CH2O-CH3, -C?C-CH2N(CH3)2, -C?C-Si(CH3)3, hidroksiC1-6alkila, hidroksiC2-6alkenila, hidroksiC2-6alkinila, cijanoC1-6alkila, cijanoC2-6alkenila, aminokarbonilC1-6alkila, C1-6alkilsulfonilC1-6alkila, C1-6alkilsulfonilC2-6alkenila, C1-6alkilsulfonilC1-6alkinila, -PO(OC1-6alkil)2, -B(OH)2, -S-CH3, SF5, C1-6alkilsulfonila, -NR8R9, C1-6alkilNR8R9, -OR8, -C1-6alkilOR8, -CONR8R9, piperidinilC1-6alkila, piperazinilC1-6alkila, C1-6alkilpiperazinilC1-6alkila, morfolinilC1-6alkila, piperidinila, piperazinila, C1-6alkilpiperazinila, morfolinila, fenila, tienila, pirazolila, pirolila, pirolidinila, piridinila, pirimidinila, oksadiazolila, imidazolila, imidazolilC2-6alkinila, C1-6alkilimidazolilC2-6alkinila, cijanopiridinila, fenilC1-6alkila, fenilC2-6alkenila, morfolinilC1-6alkila, C1-6alkiloksifenila, trihaloC1-6alkilfenila, metilpirazolila, halopirimidinila ili dimetilaminopirolidinila; R2 je vodik, metil, etil, propil, C3-6cikloalkil, C3-6cikloalkilmetil, fluor, fenil, cijanofenil ili trifluorometil; R3 je metil, etil, propil, hidroksimetil, halo, trifluorometil, metiloksi ili C1-6alkilkarbonil; R4 je vodik, halo, metil, aminokarbonil, hidroksiaminokarbonil, NR8R9C1-6alkil-, cijanometil, hidroksimetil ili Het; svaki R5, R6 i R7 je neovisno oda

Claims (15)

1. Spoj formule (I), [image] njegovi N-oksidni oblici, farmaceutski prihvatljive adicijske soli i stereokemijski izomerni oblici, naznačen time da m je 0, 1 ili 2 i kada m je 0 tada je namjeravana direktna veza; n je 0, 1, 2, 3 ili 4 i kada n je 0 tada je namjeravana direktna veza; X je direktna veza, CR10R11, (C=O)NR8, NR8, O ili C≡C; R1 je aril ili Het; pri čemu aril je fenil ili naftalenil; pri čemu Het je tienil, pirolil, pirolinil, oksazolil, tiazolil, imidazolil, pirazolil, izoksazolil, izotiazolil, oksadiazolil, triazolil, tetrazolil, tiadiazolil, furanil, piperidinil, piridinil, piridazinil, pirimidinil, piperazinil, pirazinil, triazinil, indolizinil, azaindolizinil, indolil, indolinil, benzotienil, indazolil, benzoksazolil, benzimidazolil, benzofuranil, benzotiazolil, benzotriazolil, kromanil, purinil, kinolinil, cinolinil, ftalazinil, kinazolinil, kinoksazolinil, naftiridinil ili pteridinil; dva atoma ugljika na arilu ili Het mogu biti premoštena (tj. formiraju bi- ili triciklički dio) sa dvovalentnim radikalom odabranim od         -O-CH2-CH2-O- (a-1),         -CH2-O-CH2-O- (a-2),         -O-CH2-CH2- CH2- (a-3),         -O-CH2-CH2-NR8- (a-4),         -O-CR82-O- (a-5),         -O-CH2-CH2- (a-6),         -CH2-N-CH2-CH2- (a-7),         -(CH2)3- (a-8), ili         -(CH2)4- (a-9); svaki aril, Het, premošteni aril ili premošteni Het može biti supstituiran sa jednim, dva, tri, četiri ili pet supstituenata koji su svaki nezavisno odabrani od vodika, halo, cijano, nitro, hidroksikarbonila, C1-6alkila, C2-6alkenila, C2-6alkinila, C3-6cikloalkila, aminoC3-6cikloalkila, haloC1-6alkila, trihaloC1-6alkila, C1-6alkilkarbonila, C1-6alkiloksikarbonila, C2-6alkenilkarbonila, oksima, C1-6alkiloksima, amidoksima, -C≡C-CH2O-CH3, -C≡C-CH2N(CH3)2, -C≡C-Si(CH3)3, hidroksiC1-6alkila, hidroksiC2-6alkenila, hidroksiC2-6alkinila, cijanoC1-6alkila, cijanoC2-6alkenila, aminokarbonilC1-6alkila, C1-6alkilsulfonilC1-6alkila, C1-6alkilsulfonilC2-6alkenila, C1-6alkilsulfonilC1-6alkinila, -PO(OC1-6alkil)2, -B(OH)2, -S-CH3, SF5, C1-6alkilsulfonila, -NR8R9, C1-6alkilNR8R9, -OR8, -C1-6alkilOR8, -CONR8R9, piperidinilC1-6alkila, piperazinilC1-6alkila, C1-6alkilpiperazinilC1-6alkila, morfolinilC1-6alkila, piperidinila, piperazinila, C1-6alkilpiperazinila, morfolinila, fenila, tienila, pirazolila, pirolila, pirolidinila, piridinila, pirimidinila, oksadiazolila, imidazolila, imidazolilC2-6alkinila, C1-6alkilimidazolilC2-6alkinila, cijanopiridinila, fenilC1-6alkila, fenilC2-6alkenila, morfolinilC1-6alkila, C1-6alkiloksifenila, trihaloC1-6alkilfenila, metilpirazolila, halopirimidinila ili dimetilaminopirolidinila; R2 je vodik, metil, etil, propil, C3-6cikloalkil, C3-6cikloalkilmetil, fluor, fenil, cijanofenil ili trifluorometil; R3 je metil, etil, propil, hidroksimetil, halo, trifluorometil, metiloksi ili C1-6alkilkarbonil; R4 je vodik, halo, metil, aminokarbonil, hidroksiaminokarbonil, NR8R9C1-6alkil-, cijanometil, hidroksimetil ili Het; svaki R5, R6 i R7 je neovisno odabran od vodika, halo, C1-6alkiloksi, cijano, C1-6alkila, -OCH2CH2NR8R9, -CH2OCH2CH2NR8R9, -OCH2CH2CH2NR8R9 ili C1-6alkiloksiC1-6alkiloksi; svaki R8 i R9 je neovisno odabran od vodika, halo, C1-6alkila, C2-6alkenila, C2-6alkinila, karbonila, C1-6alkilsulfonilC1-6alkila, C1-6alkiloksiC1-6alkil, hidroksiC1-6alkila, dihidroksiC1-6alkila, cijanoC1-6alkila, trihaloC1-6alkila, fenilC1-6alkila, (diC1-6alkil)aminoC1-6alkila, C1-6alkilsulfonila, morfolinilC1-6alkila, morfolinilkarbonila, piperazinilC1-6alkila, C1-6alkilpiperazinilC1-6alkila, piperidinilC1-6alkila, tiomorfolinilC1-6alkila, C3-6cikloalkilmetila, piridinila, pirimidinila, fenila, halofenila, oksanilC1-6alkila, C1-6alkilsulfonilC1-6alkila ili C1-6alkilkarbonilaminoC1-6alkila; svaki R10 i R11 je neovisno odabran od vodika, metila, hidroksila, ili uzeti zajedno sa atomom ugljika na koji su spojeni mogu formirati ciklopropilni prsten ili radikal formule C(=O).
2. Spoj formule (I) prema zahtjevu 1 naznačen time da m je 0; X je CR10R11 i tada n je 0; ili X je O i tada n je 2; Het je tienil, oksazolil, tiazolil, oksadiazolil, triazolil, tiadiazolil, furanil, piridinil, pirimidinil, azaindolizinil, indazolil, benzoksazolil, benzofuranil, benzotiazolil, benzotriazolil, kinolinil ili kinoksazolinil; dva atoma ugljika na arilu ili Het mogu biti premoštena sa dvovalentnim radikalom odabranim od (a-1), (a-2), (a-4) ili (a-5); svaki aril ili Het ili premošteni aril može biti supstituiran sa jednim, dva, tri, četiri ili pet supstituenata koji su svaki nezavisno odabrani od vodika, halo, cijano, nitro, amino, hidroksikarbonila, C1-6alkila, haloC1-6alkila, trihaloC1-6alkila, C1-6alkilkarbonila, C1-6alkiloksikarbonila, C2-6alkinila, -CH=CH-CN, hidroksiC1-6alkila, cijanoC1-6alkila, -PO(OC1-6alkil)2, -S-CH3, C1-6alkilsulfonila, -NR8R9, -CH2NR8R9, -OR8, -CH2OR8, -CONR8R9, morfolinilC1-6alkila, piperidinila, piperazinila, C1-6alkilpiperazinila, morfolinila, fenila, C1-6alkiloksifenila, pirazolila, metilpirazolila ili oksadiazolila; R2 je metil, etil, propil, C3-6cikloalkil, C3-6cikloalkilmetil, fenil ili cijanofenil; R3 je metil, etil ili hidroksimetil; R4 je vodik; svaki R5, R6 i R7 je vodik; ili svaki R8 i R9 je neovisno odabran od vodika, C1-6alkila, C1-6alkiloksiC1-6alkila, dihidroksiC1-6alkila, cijanoC1-6alkila, trihaloC1-6alkila, fenilC1-6alkila, C1-6alkilsulfonila, morfolinilC1-6alkila, morfolinilkarbonila, piperazinilC1-6alkila ili C1-6alkilpiperazinilC1-6alkila.
3. Spoj formule (I) prema zahtjevu 1 naznačen time da Het je tienil, tiazolil, imidazolil, oksadiazolil, triazolil, tiadiazolil, furanil, piperidinil, piridinil, pirimidinil, piperazinil, azaindolizinil, indolil, indolinil, benzotienil, indazolil, benzoksazolil, benzimidazolil, benzofuranil, benzotiazolil, benzotriazolil, kinolinil, cinolinil ili kinoksazolinil; svaki aril, Het, premošteni aril ili premošteni Het može biti supstituiran sa jednim, dva, tri, četiri ili pet supstituenata koji su svaki nezavisno odabrani od vodika, halo, cijano, nitro, hidroksikarbonila, C1-6alkila, C2-6alkenila, C2-6alkinila, aminoC3-6cikloalkila, trihaloC1-6alkila, C1-6alkilkarbonila, C1-6alkiloksikarbonila, oksima, C1-6alkiloksima, amidoksima, -C≡C-CH2O-CH3, -C≡C-CH2N(CH3)2, -C≡C-Si(CH3)3, hidroksiC2-6alkenila, hidroksiC2-6alkinila, cijanoC1-6alkila, cijanoC2-6alkenila, C1-6alkilsulfonilC1-6alkila, C1-6alkilsulfonilC2-6alkenila, -PO(OC1-6alkil)2, -S-CH3, SF5, C1-6alkilsulfonila, -NR8R9, C1-6alkilNR8R9, -OR8, -C1-6alkilOR8, -CONR8R9, C1-6alkilpiperazinilC1-6alkila, piperidinila, piperazinila, C1-6alkilpiperazinila, morfolinila, fenila, pirolila, pirolidinila, piridinila, oksadiazolila, C1-6alkilimidazolilC2-6alkinila, cijanopiridinila, fenilC2-6alkenila, morfolinilC1-6alkila, C1-6alkiloksifenila, trihaloC1-6alkilfenila, metilpirazolila, halopirimidinila ili dimetilaminopirolidinila; R2 je metil, etil, propil, C3-6cikloalkil, C3-6cikloalkilmetil, fluor, fenil ili cijanofenil; R3 je metil, etil, propil, hidroksimetil, metiloksi ili C1-6alkilkarbonil; R4 je vodik, halo ili metil; svaki R5, R6 i R7 je neovisno odabran od vodika, halo, C1-6alkiloksi, C1-6alkila ili C1-6alkiloksiC1-6alkiloksi; svaki R8 i R9 je neovisno odabran od vodika, C1-6alkila, C2-6alkinila, C1-6alkiloksiC1-6alkila, hidroksiC1-6alkila, dihidroksiC1-6alkila, cijanoC1-6alkila, trihaloC1-6alkila, fenilC1-6alkila, C1-6alkilsulfonila, morfolinilC1-6alkil, morfolinilkarbonila, piperazinilC1-6alkila, C1-6alkilpiperazinilC1-6alkila, C3-6cikloalkilmetila, piridinila, pirimidinila, fenila, halofenila, oksanilC1-6alkila ili C1-6alkilsulfonilC1-6alkila; ili svaki R10 i R11 je neovisno odabran od vodika ili metila.
4. Spoj formule (I) prema bilo kojem od zahtjeva 1 do 3 naznačen time da m je 0 ili I; n je 0 ili 1; X je direktna veza, CR10R11 ili NR8; R1 je fenil, tiadiazolil, piridinil ili pirimidinil; R1 je fenil i je premošten sa dvovalentnim radikalom odabranim od (a-3) ili (a-8); svaki fenil, premošteni fenil, tiadiazolil, piridinil ili pirimidinil može biti supstituiran sa jednim ili dva supstituenta koji su svaki neovisno odabrani od vodika, halo, cijano, C1-6alkila, C2-6alkinila, hidroksiC2-6alkenila ili -OR8; R2 je metil; R3 je metil ili etil; R4 je vodik; svaki R5, R6 i R7 je vodik; svaki R8 je neovisno odabran od vodika ili C1-6alkila i svaki R10 i R11 je vodik.
5. Spoj formule (I) prema bilo kojem od zahtjeva 1, 3 i 4 naznačen time da spoj je Spoj br. 34, Spoj br. 36, Spoj br. 42, Spoj br. 43, Spoj br. 3, Spoj br. 51, Spoj br. 53, Spoj br. 46, Spoj br. 381, Spoj br. 242, Spoj br. 246, Spoj br. 183, Spoj br. 253, Spoj br. 207, Spoj br. 232, Spoj br. 204, Spoj br. 174 ili Spoj br. 252. [image]
6. Spoj formule (I) prema bilo kojem od zahtjeva 1 do 5 naznačen time da je za uporabu kao lijek.
7. Farmaceutski pripravak naznačen time da sadrži farmaceutski prihvatljive nosače i kao aktivni sastojak terapeutski učinkovitu količinu spoja formule (I) prema bilo kojem od zahtjeva 1 do 5.
8. Uporaba spoja prema bilo kojem od zahtjeva 1 do 5 naznačena time da je za proizvodnju lijeka za liječenje oštećenja tkiva koje proizlazi iz oštećenja stanice ili smrti zbog nekroze ili apoptoze, za liječenje oštećenja živčanog tkiva nastalih zbog ishemije i reperfuzijske ozljede, neuroloških poremećaja i neurodegenerativnih bolesti, za liječenje krvožilnog infarkta; za liječenje kardiovaskularnih bolesti, za liječenje mišićne degeneracije povezane sa starenjem, AIDS-a, imunoloških bolesti povezanih sa starenjem, upale, gihta, artritisa, ateroskleroza, kaheksije, raka, degenerativnih bolesti skeletnih mišića koje uključuju replikativno starenje, dijabetes, traumu glave, poremećaje ulceroznog kolitisa, mišićnu distrofiju, osteoartritis, osteoporozu, kroničnu i/ili akutnu bol, zatajenje bubrega, ishemiju mrežnice, septički šok, te starenje kože; za produljivanje trajanja života i proliferativnog kapaciteta stanica; za promjenu ekspresije gena starih stanica; za kemosenzitiziranje i/ili radiosenzitiziranje tumorskih stanica.
9. Uporaba spoja prema bilo kojem od zahtjeva 1 do 5 naznačena time da je za proizvodnju lijeka za liječenje raka.
10. Uporaba prema zahtjevu 8 i zahtjevu 9 naznačena time da liječenje uključuje kemosenzitiziranje.
11. Uporaba prema zahtjevima 8 i 9 naznačena time da liječenje uključuje radiosenzitiziranje.
12. Kombinirani spoj prema bilo kojem od zahtjeva 1 do 5 naznačen time da je kombinirana sa kemoterapeutskim sredstvom ili antitumorskim sredstvom.
13. Postupak za dobivanje spoja formule (I) prema zahtjevu 1, naznačen time da sadrži a) reakciju intermedijera formule (II) sa odgovarajućim reagensom u reakcijski-inertnom otapalu uz dobivanje spoja formule (I) [image] b) reakciju intermedijera formule (V-a) uz dodavanje suviška baze, u prisutnosti intermedijera formule (VI), pri čemu Halo je kloro ili bromo, u pogodnom otapalu. [image]
14. Spoj formule (II) [image] njegovi N-oksidni oblici, farmaceutski prihvatljive adicijske soli i stereokemijski izomerni oblici, naznačen time da m je 0, 1 ili 2 i kada n je 0 tada je namjeravana direktna veza; n je 0, 1, 2, 3 ili 4 i kada n je 0 tada je namjeravana direktna veza; X je direktna veza, CR10R11, (C=O)NR8, NR8, O ili C≡C; R1 je aril ili Het; pri čemu aril je fenil ili naftalenil; pri čemu Het je tienil, pirolil, pirolinil, oksazolil, tiazolil, imidazolil, pirazolil, izoksazolil, izotiazolil, oksadiazolil, triazolil, tetrazolil, tiadiazolil, furanil, piperidinil, piridinil, piridazinil, pirimidinil, piperazinil, pirazinil, triazinil, indolizinil, azaindolizinil, indolil, indolinil, benzotienil, indazolil, benzoksazolil, benzimidazolil, benzofuranil, benzotiazolil, benzotriazolil, kromanil, purinil, kinolinil, cinolinil, ftalazinil, kinazolinil, kinoksazolinil, naftiridinil ili pteridinil; dva atoma ugljika na arilu ili Het mogu biti premoštena (tj. formiraju bi- ili triciklički dio) sa dvovalentnim radikalom odabranim od         -O-CH2-CH2-O- (a-1),         -CH2-O-CH2-O- (a-2),         -O-CH2-CH2- CH2- (a-3),         -O-CH2-CH2-NR8- (a-4),         -O-CR82-O- (a-5),         -O-CH2-CH2- (a-6),         -CH2-N-CH2-CH2- (a-7),         -(CH2)3- (a-8), ili         -(CH2)4- (a-9); svaki aril, Het, premošteni aril ili premošteni Het može biti supstituiran sa jednim, dva, tri, četiri ili pet supstituenata koji su svaki nezavisno odabrani od vodika, halo, cijano, nitro, hidroksikarbonila, C1-6alkila, C2-6alkenila, C2-6alkinila, C3-6cikloalkila, aminoC3-6cikloalkila, haloC1-6alkila, trihaloC1-6alkila, C1-6alkilkarbonila, C1-6alkiloksikarbonila, C2-6alkenilkarbonila, oksima, C1-6alkiloksima, amidoksima, -C≡C-CH2O-CH3, -C≡C-CH2N(CH3)2, -C≡C-Si(CH3)3, hidroksiC1-6alkila, hidroksiC2-6alkenila, hidroksiC2-6alkinila, cijanoC1-6alkila, cijanoC2-6alkenila, aminokarbonilC1-6alkila, C1-6alkilsulfonilC1-6alkila, C1-6alkilsulfonilC2-6alkenila, C1-6alkilsulfonilC1-6alkinila,-PO(OC1-6alkil)2, -B(OH)2, -S-CH3, SF5, C1-6alkilsulfonila, -NR8R9, C1-6alkilNR8R9, -OR8, -C1-6alkilOR8, -CONR8R9, piperidinilC1-6alkila, piperazinilC1-6alkila, C1-6alkilpiperazinilC1-6alkila, morfolinilC1-6alkila, piperidinila, piperazinila, C1-6alkilpiperazinila, morfolinila, fenila, tienila, pirazolila, pirolila, pirolidinila, piridinila, pirimidinila, oksadiazolila, imidazolila, imidazolilC2-6alkinila, C1-6alkilimidazolilC2-6alkinila, cijanopiridinila, fenilC1-6alkila, fenilC2-6alkenila, morfolinilC1-6alkila, C1-6alkiloksifenila, trihaloC1-6alkilfenila, metilpirazolila, halopirimidinila ili dimetilaminopirolidinila; R2 je vodik, metil, etil, propil, C3-6cikloalkil, C3-6cikloalkilmetil, fluor, fenil, cijanofenil ili trifluorometil; R3 je metil, etil, propil, hidroksimetil, halo, trifluorometil, metiloksi ili C1-6alkilkarbonil; R4 je vodik, halo, metil, aminokarbonil, hidroksiaminokarbonil, NR8R9C1-6alkil-, cijanometil, hidroksimetil ili Het; svaki R5, R6 i R7 je neovisno odabran od vodika, halo, C1-6alkiloksi, cijano, C1-6alkila, -OCH2CH2NR8R9, -CH2OCH2CH2NR8R9, -OCH2CH2CH2NR8R9 ili C1-6alkiloksiC1-6alkiloksi; svaki R8 i R9 je neovisno odabran od vodika, halo, C1-6alkila, C2-6alkenila, C2-6alkinila, karbonila, C1-6alkilsulfonilC1-6alkila, C1-6alkiloksiC1-6alkila, hidroksiC1-6alkila, dihidroksiC1-6alkila, cijanoC1-6alkila, trihaloC1-6alkila, fenilC1-6alkila, (diC1-6alkil)aminoC1-6alkila, C1-6alkilsulfonila, morfolinilC1-6alkila, morfolinilkarbonila, piperazinilC1-6alkila, C1-6alkilpiperazinilC1-6alkila, piperidinilC1-6alkila, tiomorfolinilC1-6alkila, C3-6cikloalkilmetila, piridinila, pirimidinila, fenila, halofenila, oksanilC1-6alkila, C1-6alkilsulfonilC1-6alkila ili C1-6alkilkarbonilaminoC1-6alkila; svaki R10 i R11 je neovisno odabran od vodika, metila, hidroksila, ili uzeti zajedno sa atomom ugljika na koji su spojeni mogu formirati ciklopropilni prsten ili radikal formule C(=O).
15. Postupak za dobivanje spoja formule (11) prema zahtjevu 14, naznačen time da sadrži a) konverziju ketonske skupine intermedijera formule (III) u hidroksi skupinu, sa odgovarajućim redukcijskim sredstvom, u pogodnom otapalu, uz formiranje spojeva formule (II), pri čemu R3 je hidroksimetil, koji se ovdje nazivaju intermedijeri formule (II-a), [image] b) dodavanje kalijeve soli 2-metil-2-propanola, u intermedijere formule (V-b) u prisutnosti intermedijera formule (VI), pri čemu Halo je kloro ili bromo, u pogodnom otapalu, uz formiranje spojeva formule (II), pri čemu R3 je metil, etil ili propil i R2 je metil, etil, C3-6cikloalkil ili fenil, koji se ovdje nazivaju intermedijeri formule (II-b), [image] c) dodavanje kalijeve soli 2-metil-2-propanola, u intermedijere formule (VII) u prisutnosti intermedijera formule (VIII), pri čemu Halo je kloro ili bromo, u pogodnom otapalu, uz formiranje spojeva formule (II), pri čemu R3 je metil, etil ili propil i R2 je propil ili C3-6cikloalkilmetil, koji se ovdje nazivaju intermedijeri formule (II-c). [image]
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