HRP20100418T1 - Novi spojevi aminobenzofenona - Google Patents

Novi spojevi aminobenzofenona Download PDF

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Publication number
HRP20100418T1
HRP20100418T1 HR20100418T HRP20100418T HRP20100418T1 HR P20100418 T1 HRP20100418 T1 HR P20100418T1 HR 20100418 T HR20100418 T HR 20100418T HR P20100418 T HRP20100418 T HR P20100418T HR P20100418 T1 HRP20100418 T1 HR P20100418T1
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Croatia
Prior art keywords
compound
chloro
phenylamino
methyl
difluoro
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HR20100418T
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English (en)
Inventor
Rytter Ottosen Erik
Marie Horneman Anne
Liang Xifu
Christian Schou Soren
Elisabeth Havez Sophie
Peter Sabroe Thomas
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Leo Pharma A/S
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Publication of HRP20100418T1 publication Critical patent/HRP20100418T1/hr

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    • C07C225/22—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
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Abstract

Spoj opće formule Inaznačen time, štoR1 je halogen, hidroksi, merkapto, trifluorometil, amino, C1-4alkil, C2-4alkenil, C2-4alkinil, C1-4alkoksi, C1-4alkiltio, C1-6alkilamino, C1-4alkoksikarbonil, cijano, -CONH2 ili nitro; R2 je halogen, amino, C1-4alkil ili nitro; R3 predstavlja jedan ili više jednakih ili različitih supstituenata iz skupine koja obuhvaća vodik, halogen, C1-4alkil ili C1-4alkoksi; R4 je fluor; jedan od R5 i R6 je -COOH, -C(O)NHOH, -C(O)NHNH2, Y2R9, Y2R9Y3R10, C1-6alkil-Y2R9, C1-6alkil-Y2R9Y3R10, C2-6alkenil-Y2R9, C2-6alkenil-Y2R9Y3R10, Y2R9-C1-6alkil-Y3R10, Y2R9-C2-6alkenil-Y3R10, C3-12karbociklil-Y2R9, C3-12karbociklil-Y2R9Y3R10, C1-12heterociklil-Y2R9, C1-12heterociklil-Y2R9Y3R10, C3-12karbociklil-C1-6alkil-Y2R9, C3-12karbociklil-C1-6alkil-Y2R9Y3R10, C1-12heterociklil-C1-6alkil-Y2R9, C1-12heterociklil-C1-6alkil-Y2R9Y3R10, C3-12karbociklil-C1-6alkil-Y3R10, C1-12heterociklil-C1-6alkil-Y3R10, C1-12heterociklil-C1-10alkil, C3-12karbociklil-C1-10alkil, C1-10alkil-C1-12heterociklil, C1-10alkil-C3-12karbociklil, C1-10alkil, C2-10alkenil, C2-10alkinil, C3-12karbociklil ili C1-12heterociklil, od kojih je svaki po izboru supstituiran jednim ili više jednakih ili različitih supstituenata koje predstavlja R7, a drugi je vodik, halogen, hidroksi, merkapto, trifluorometil, amino, C1-4alkil, C2-4alkenil, C2-4alkinil, C1-4alkoksi, C1-4alkiltio, C1-6alkilamino, C1-4alkoksikarbonil, cijano, -CONH2 ili nitro; uz uvjet da kada je R5 ili R6 fenil, C1-5alkil ili C2-3alkenil, tada je R5 ili R6 supstituiran jednim ili više jednakih ili različitih supstituenata koje predstavlja R7 (osim tri fluora kada je R5 ili R6 metil), R7 je halogen, hidroksi, merkapto, trifluorometil, amino, C1-4alkil, C1-6hidroksialkil, C1-4alkoksi, C1-4alkiltio, C1-6alkilamino, C1-4alkoksikarbonil, C1-9trialkilamonij u vezi s anionom, cijano, azidom, nitro, -S(O)2NH2, -S(O)2NRaRb, -S(O)2R, -COOH, - CONH2, -NRaC(O)R', -CONHR' ili -CONRR', pri čemu su R i R' isti ili različiti, a svaki predstavlja vodik ili C1-3alkil; Ra, Rb i RC su isti ili različiti, a svaki predstavlja vodik, C1-4alkil, C2-4alkenil, C2-4alkinil, C3-8karbociklil, C1-12heterociklil ili aril, svaki od C1-4alkil, C2-4alkenil, C2-4alkinil, C3-8karbociklil, C1-12heterociklil ili aril može po izboru biti supstituiran jednim ili više jednakih ili različitih supstituenata koje predstavlja R7;Y2 je -O-, -S-, -S(O)-, -S(O)2-, -NRa-, -NRaC(O)NRb-, -NRaC(O)-, -C(O)NRa-, -C(O)NRaO-, -C(O)-, -NRaC(O)O-, -NRaS(O)2-, -OC(O)-, -C(O)O-, -C(O)NRaNRbC(S)NRC-, -C(O)NRaNRb- ili -S(O)2NRa-; R9 je C1-10alkil-C1-12heterociklil, C1-10alkil-C3-12karbociklil, C1-10alkil, C2-10alkenil, C2-10alkinil, C3-12karbociklil, C1-12heterociklil, C3-12karbociklil-C1-10alkil ili C1-12heterociklil-C1-10alkil, C3-6karbociklil-C1-6alkenil, C3-6karbociklil-C2-6alkinil, od kojih je svaki po izboru supstituiran jednim ili više jednakih ili različitih supstituenata koje predstavlja R7,uz uvjet da kada je Y2 -O-, -NRa-, -S- ili -C(O)O-, i R9 je C1-6alkil, taj

Claims (38)

1. Spoj opće formule I [image] naznačen time, što R1 je halogen, hidroksi, merkapto, trifluorometil, amino, C1-4alkil, C2-4alkenil, C2-4alkinil, C1-4alkoksi, C1-4alkiltio, C1-6alkilamino, C1-4alkoksikarbonil, cijano, -CONH2 ili nitro; R2 je halogen, amino, C1-4alkil ili nitro; R3 predstavlja jedan ili više jednakih ili različitih supstituenata iz skupine koja obuhvaća vodik, halogen, C1-4alkil ili C1-4alkoksi; R4 je fluor; jedan od R5 i R6 je -COOH, -C(O)NHOH, -C(O)NHNH2, Y2R9, Y2R9Y3R10, C1-6alkil-Y2R9, C1-6alkil-Y2R9Y3R10, C2-6alkenil-Y2R9, C2-6alkenil-Y2R9Y3R10, Y2R9-C1-6alkil-Y3R10, Y2R9-C2-6alkenil-Y3R10, C3-12karbociklil-Y2R9, C3-12karbociklil-Y2R9Y3R10, C1-12heterociklil-Y2R9, C1-12heterociklil-Y2R9Y3R10, C3-12karbociklil-C1-6alkil-Y2R9, C3-12karbociklil-C1-6alkil-Y2R9Y3R10, C1-12heterociklil-C1-6alkil-Y2R9, C1-12heterociklil-C1-6alkil-Y2R9Y3R10, C3-12karbociklil-C1-6alkil-Y3R10, C1-12heterociklil-C1-6alkil-Y3R10, C1-12heterociklil-C1-10alkil, C3-12karbociklil-C1-10alkil, C1-10alkil-C1-12heterociklil, C1-10alkil-C3-12karbociklil, C1-10alkil, C2-10alkenil, C2-10alkinil, C3-12karbociklil ili C1-12heterociklil, od kojih je svaki po izboru supstituiran jednim ili više jednakih ili različitih supstituenata koje predstavlja R7, a drugi je vodik, halogen, hidroksi, merkapto, trifluorometil, amino, C1-4alkil, C2-4alkenil, C2-4alkinil, C1-4alkoksi, C1-4alkiltio, C1-6alkilamino, C1-4alkoksikarbonil, cijano, -CONH2 ili nitro; uz uvjet da kada je R5 ili R6 fenil, C1-5alkil ili C2-3alkenil, tada je R5 ili R6 supstituiran jednim ili više jednakih ili različitih supstituenata koje predstavlja R7 (osim tri fluora kada je R5 ili R6 metil), R7 je halogen, hidroksi, merkapto, trifluorometil, amino, C1-4alkil, C1-6hidroksialkil, C1-4alkoksi, C1-4alkiltio, C1-6alkilamino, C1-4alkoksikarbonil, C1-9trialkilamonij u vezi s anionom, cijano, azidom, nitro, -S(O)2NH2, -S(O)2NRaRb, -S(O)2R, -COOH, - CONH2, -NRaC(O)R', -CONHR' ili -CONRR', pri čemu su R i R' isti ili različiti, a svaki predstavlja vodik ili C1-3alkil; Ra, Rb i RC su isti ili različiti, a svaki predstavlja vodik, C1-4alkil, C2-4alkenil, C2-4alkinil, C3-8karbociklil, C1-12heterociklil ili aril, svaki od C1-4alkil, C2-4alkenil, C2-4alkinil, C3-8karbociklil, C1-12heterociklil ili aril može po izboru biti supstituiran jednim ili više jednakih ili različitih supstituenata koje predstavlja R7; Y2 je -O-, -S-, -S(O)-, -S(O)2-, -NRa-, -NRaC(O)NRb-, -NRaC(O)-, -C(O)NRa-, -C(O)NRaO-, -C(O)-, -NRaC(O)O-, -NRaS(O)2-, -OC(O)-, -C(O)O-, -C(O)NRaNRbC(S)NRC-, -C(O)NRaNRb- ili -S(O)2NRa-; R9 je C1-10alkil-C1-12heterociklil, C1-10alkil-C3-12karbociklil, C1-10alkil, C2-10alkenil, C2-10alkinil, C3-12karbociklil, C1-12heterociklil, C3-12karbociklil-C1-10alkil ili C1-12heterociklil-C1-10alkil, C3-6karbociklil-C1-6alkenil, C3-6karbociklil-C2-6alkinil, od kojih je svaki po izboru supstituiran jednim ili više jednakih ili različitih supstituenata koje predstavlja R7, uz uvjet da kada je Y2 -O-, -NRa-, -S- ili -C(O)O-, i R9 je C1-6alkil, taj C1-6alkil je supstituiran jednim ili više jednakih ili različitih supstituenata koje predstavlja R7; Y3 je -O-, -S-, -S(O)-, -S(O)2-, -NRa-, -NRaC(O)NRb-, -NRaC(O)-, -C(O)NRa-, -C(O)NRaO-, -C(O)-, -NRaC(O)O-, -NRaS(O)2-, -OC(O)- ili -C(O)O-; R10 je C1-10alkil-C1-12heterociklil, C1-10alkil-C3-12karbociklil, C1-10alkil, C2-10alkenil, C2-10alkinil, C3-12karbociklil ili C1-12heterociklil, od kojih je svaki po izboru supstituiran jednim ili više jednakih ili različitih supstituenata koje predstavlja R7; ili, kada je jedan od R5 i R6 skupina -C(O)NRaR9, Ra i R9 zajedno s atomom dušika za koji su vezani tvore C1-12heterociklički prsten, koji po izboru sadrži jedan ili više dodatnih heteroatoma izabranih iz skupine koja obuhvaća O, S i N, po izboru supstituirane jednim ili više supstituenata koje predstavlja R7; ili njegova farmaceutski prihvatljiva sol, solvat ili ester.
2. Spoj prema zahtjevu 1, naznačen time što je R1 halogen, trifluorometil, C1-4alkil, C1-4alkoksi ili nitro.
3. Spoj prema zahtjevu 2, naznačen time što je R1 metil, etil, metoksi, etoksi, brom, fluor ili klor.
4. Spoj prema bilo kojem od zahtjeva 1-3, naznačen time što je R2 metil, etil, nitro, brom, fluor ili klor.
5. Spoj prema bilo kojem od zahtjeva 1-4, naznačen time što je R3 vodik, metil, etil, metoksi, etoksi, brom, fluor ili klor.
6. Spoj prema bilo kojem od zahtjeva 1-5, naznačen time što R3 predstavlja jedan supstituent.
7. Spoj prema zahtjevu 6, naznačen time što je R3 u odnosu na R4 u meta položaju, a u odnosu na -NH je u para položaju, ili je R3 u odnosu na R4 u meta položaju, a u odnosu na -NH je u orto položaju, ili je R3 u odnosu na R4 u orto položaju, a u odnosu na -NH je u meta položaju.
8. Spoj prema bilo kojem od zahtjeva 1-7, naznačen time što je R3 fluor.
9. Spoj prema bilo kojem od zahtjeva 1-8, naznačen time što je R7 halogen, hidroksi, amino, -S(O)2CH3, trifluorometil, cijano, C1-4hidroksialkil, C1-4alkoksi, C1-4alkil, C1-4alkiltio, C1-4alkilamino, C1-4alkoksikarbonil, -COOH, -CONH2, -S(O)2NH2, azido, -CONHR' ili -CONRR', pri čemu su R i R' kako je naznačeno u zahtjevu 1.
10. Spoj prema zahtjevu 9, naznačen time što je R7 metil, etil, metoksi, etoksi, hidroksi, metoksikarbonil, etoksikarbonil, dimetilamino, etilamino, amino, -COOH, fluor, klor, brom, -CONH2, -S(O)2NH2, azido, metiltio, -S(O)2CH3, trifluorometil, cijano ili hidroksimetil.
11. Spoj prema bilo kojem od zahtjeva 1-10, naznačen time što jedan od R5 i R6 je Y2R9, C1-4alkil-Y2R9, Y2R9Y3R10, C1-4alkil-Y2R9Y3R10, C2-4alkenil-Y2R9, C2-4alkenil-Y2R9Y3R10, Y2R9-C1-4alkil-Y3R10, Y2R9-C2-4alkenil-Y3R10, C1-6heterociklil-C1-4alkil-Y2R9, C1-4alkil-C1-6heterociklil, C1-4alkil-C3-6karbociklil, C3-6karbociklil-C1-4alkil, C1-4alkil supstituiran s R7, C2-4alkenil, C2-4alkinil, C3-6karbociklil, C1-6heterociklil, -COOH, -C(O)NHOH ili -C(O)NHNH2, a drugi je vodik, halogen, C1-4alkil ili C1-4alkoksi.
12. Spoj prema zahtjevu 11, naznačen time što R5 je Y2R9, C1-4alkil-Y2R9, Y2R9Y3R10, C1-4alkil-Y2R9Y3R10, C2-4alkenil-Y2R9, C2-4alkenil-Y2R9Y3R10, Y2R9-C1-4alkil-Y3R10, Y2R9-C2-4alkenil-Y3R10, C1-6heterociklil-C1-4alkil-Y2R9, C1-4alkil-C1-6heterociklil, C1-4alkil-C3-6karbociklil, C3-6karbociklil-C1-4alkil, C1-4alkil supstituiran s R7, C2-4alkenil, C2-4alkinil, C3-6karbociklil, C1-6heterociklil, -COOH, -C(O)NHOH ili -C(O)NHNH2, a R6 je vodik, halogen, C1-4alkil ili C1-4alkoksi.
13. Spoj prema zahtjevu 11, naznačen time što jedan od R5 i R6 je Y2R9, Y2R9Y3R10, fenil, metilfenil, propenil, metil-Y2R9, tetrazol, etinil, triazol, tiadiazol, dihidrooksazol, -COOH, -C(O)NHOH ili -C(O)NHNH2, a drugi je vodik, fluor, klor, metil ili metoksi.
14. Spoj prema bilo kojem od zahtjeva 1-13, naznačen time što je R6 vodik.
15. Spoj prema bilo kojem od zahtjeva 1-11 ili 13, naznačen time što je R5 vodik.
16. Spoj prema bilo kojem od zahtjeva 1-15, naznačen time što Y2 je -O-, -NRa-, -NRaC(O)NRb-, -NRaC(O)-, -C(O)NRa-, -C(O)NRaO-, -C(O)-, -NRaC(O)O-, -NRaS(O)2-, -C(O)NRaNRb- ili -S(O)2NRa-.
17. Spoj prema bilo kojem od zahtjeva 1-16, naznačen time što Y3 je -O-, -NRaC(O)-, -C(O)NRa-, -C(O)-, -C(O)O- ili -NRaC(O)O-.
18. Spoj prema bilo kojem od zahtjeva 1-17, naznačen time što R9 je C1-4alkil-C1-6heterociklil, C1-4alkil-C3-6karbociklil, C1-6alkil, C2-4alkenil, C2-4alkinil, C3-10karbociklil, C1-6heterociklil, C3-6karbociklil-C1-6alkil, C1-6heterociklil-C1-6alkil, C3-6karbociklil-C2-4alkenil ili C3-6karbociklil-C2-4alkinil.
19. Spoj prema zahtjevima 1-18, naznačen time što R9 je C1-4heterociklil, C1-6alkil, C1-3alkil-C1-5heterociklil, C6-10karbociklil, C1-3alkil-C6karbociklil, C3alkenil, C6karbociklil-C1alkil, C6karbociklil-C3alkenil ili C6karbociklil-C2alkinil.
20. Spoj prema zahtjevu 19, naznačen time što je R9 morfolinil, propilmorfolinil, piperazinil, metil, etil, n-propil, n-butil, tert-butil, izobutil, heksil, izopropil, dimetilpropil, metiltetrahidrofuranil, metilpiridinil, etilpiperazinil, cikloheksil, propiloksopirolidinil, benzil, metilcikloheksil, propilfenil, etilmorfolinil, alil, etilfuranil, fenil, metildioksoimidazolidinil, dioksoheksahidropirimidinil, tiazolil, metilfenil, etilfenil, metildioksolanil, metiltiazolil, propenilfenil, metilfuranil, tiofenil, tetrahidropiranil ili etinilfenil.
21. Spoj prema bilo kojem od zahtjeva 1-20, naznačen time što R10 je C1-4alkil, C2-4alkenil, C3-6karbociklil ili C1-6heterociklil.
22. Spoj prema zahtjevu 21, naznačen time što je R10 metil, etil, metakril, terc-butil, tetrahidropiranil ili etenil.
23. Spoj prema bilo kojem od zahtjeva 1-22, naznačen time što navedeni heterocikl ili heterociklil sadrži jedan ili dva atoma kisika ili jedan atom sumpora, i/ili do dva atoma dušika, ili tri ili četiri atoma dušika, pri čemu su po izboru jedan ili dva fragmenta prstena CH2 zamijenjena jednim ili dva -C(O)- fragmenta.
24. Spoj prema bilo kojem od zahtjeva 1-23, naznačen time što Ra, Rb ili Rc nezavisno jedan od drugoga predstavljaju vodik, metil, etil, 2-hidroksietil ili 2-metoksietil.
25. Spoj prema bilo kojem od zahtjeva 1-24, naznačen time što se izabire iz skupine koja obuhvaća 3-[2-klor-4-(2,4-difluorfenilamino)benzoil]-N-(2-hidroksietil)-4-metilbenzamid (Spoj 115), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-N-(2-hidroksietil)-4-metilbenzamid (Spoj 120), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-4,N-dimetil-benzamid (Spoj 121), etilni ester (2-{3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-4-metil-benzoilamino}-acetilamino)-octene kiseline (Spoj 122), etilni ester {3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-4-metil-benzoilamino}-octene kiseline (Spoj 123), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-N-(2-metoksi-etil)-4-metil-benzamid (Spoj 124), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-N-cikloheksil-4-metil-benzamid (Spoj 125), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-N-etil-4-metil-benzamid (Spoj 126), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-N-(6-hidroksi-heksil)-4-metil-benzamid (Spoj 127), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)benzoil]-N-izopropil-4-metil-benzamid (Spoj 128), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-N-izobutil-4-metil-benzamid (Spoj 129), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-N-(2,2-dimetil-propil)-4-metil-benzamid (Spoj 130), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-N-(3-metoksil-propil)-4-metil-benzamid (Spoj 131), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-4-metil-N-[3-(2-okso-pirolidin-1-il)-propil]-benzamid (Spoj 132), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-N-(2-dimetilamino-etil)-4-metil-benzamid (Spoj 133), etilni ester 2-{3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-4-metil-benzoilamino}-2-metil-akrilne kiseline (Spoj 134), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-N-cis-(4-hidroksi-cikloheksil)-4-metil-benzamid (Spoj 135), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-N-trans-(4-hidroksi-cikloheksil)-4-metil-benzamid (Spoj 136), terc-butilni ester (2-{3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-4-metil-benzoilamino}-etil)-karbaminske kiseline (Spoj 137), N-(2-amino-etil)-3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-4-metil-benzamid (Spoj 138), (2-{3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-4-metil-benzoilamino}-acetilamino)-octena kiselina (Spoj 139), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2-hidroksi-etil)-4-metoksi-benzamid (Spoj 140), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2,2-difluor-etil)-4-metoksi-benzamid (Spoj 141), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2-fluor-etil)-4-metoksi-benzamid (Spoj 142), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2,3-dihidroksi-propil)-4-metoksi-benzamid (Spoj 143), N-karbamoilmetil-3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metoksi-benzamid (Spoj 144), N-karbamoilmetil-3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzamid (Spoj 145), N-benzill-3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzamid (Spoj 146), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2-fluor-etil)-4-metil-benzamid (Spoj 147), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-N-(2,2,2-trifluor-etil)-benzamid (Spoj 148), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-etil-4-metil-benzamid (Spoj 149), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-cikloheksilmetil-4-metil-benzamid (Spoj 150), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2-hidroksi-propil)-4-metil-benzamid (Spoj 151), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2,3-dihidroksi-propil)-4-metil-benzamid (Spoj 152), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(1-hidroksimetil-propil)-4-metil-benzamid (Spoj 153), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-N-(2,2,3,3,3-pentafluor-propil)-benzamid (Spoj 154), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(3-hidroksi-propil)-4-metil-benzamid (Spoj 155), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2-hidroksi-1,1-dimetil-etil)-4-metil-benzamid (Spoj 156), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2-hidroksi-1-hidroksimetil-1-metil-etil)-4-metil-benzamid (Spoj 157), etilni ester {3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzoilamino}-octene kiseline (Spoj 158), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(4-hidroksi-butil)-4-metil-benzamid (Spoj 159), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(3-hidroksi-1,1-dimetil-butil)-4-metil-benzamid (Spoj 160), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-N-(3-fenil-propil)-benzamid (Spoj 161), (R)-3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(1-hidroksimetil-3metil-butil)-4-metil-benzamid (Spoj 162), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-izopropil-4-metil-benzamid (Spoj 164), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-cikloheksil-4-metil-benzamid (Spoj 165), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2,2-difluor-etil)-4-metil-benzamid (Spoj 166), metilni ester 5-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzoilamino}-4-okso-pentanske kiseline (Spoj 167), N-[(2-karbamoil-etilkarbamoil)-metil]-3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzamid (Spoj 168), etilni ester (2-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzoilamino}-acetilamino)-octene kiseline (Spoj 169), N-alil-3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzamid (Spoj 170), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-N-(2-sulfamoil-etil)-benzamid (Spoj 171), N-(2-acetilamino-etil)-3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzamid (Spoj 172), 3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-N-(2-hidroksi-etil)-4-metoksi-benzamid (Spoj 173), 3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-N-(2-fluor-etil)-4-metoksi-benzamid (Spoj 174), 3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-N-(2,3-dihidroksi-propil)-4-metoksi-benzamid (Spoj 175), 3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-N-(3-hidroksi-propil)-4-metoksi-benzamid (Spoj 176), 3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-4-metoksi-N-fenetil-benzamid (Spoj 177), 3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-N-(2-hidroksi-1,1-dimetil-etil)-4-metoksi-benzamid (Spoj 178), 3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-4-metoksi-N-(2-morfolin-4-il-etil)-benzamid (Spoj 179), 3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-N-(2-hidroksi-1-hidroksimetil-1-metil-etil)-4-metoksi-benzamid (Spoj 180), 3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-N-(2-hidroksi-etil)-4-metoksi-N-metil-benzamid (Spoj 181), etilni ester {3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-4-metoksi-benzoilamino}-octene kiseline (Spoj 182), etilni ester (2-{3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-4-metoksi-benzoilamino}-acetilamino)-octene kiseline (Spoj 183), 3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-N,N-bis-(2-hidroksi-etil)-4-metoksi-benzamid (Spoj 184), 3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-4-metoksi-N,N-bis-(2-metoksi-etil)-benzamid (Spoj 185); 4-klor-3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2-hidroksi-etil)-benzamid (Spoj 204), N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-metoksi-propionamid (Spoj 241), N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-propionamid (Spoj 242), N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-2-(2-metoksi-etoksi)-acetamid (Spoj 243), N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-morfolin-4-il-propionamid (Spoj 244), N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-hidroksi-propionamid (Spoj 245), N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-furan-2-il-propionamid (Spoj 246), N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-2-hidroksi-benzamid (Spoj 247), N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-2-(2,5-diokso-imidazolidin-4-il)-acetamid (Spoj 248), {3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-amid 2,6-diokso-heksahidro-pirimidin-4-karboksilne kiseline (Spoj 249), 2-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil-karbamoil}-etilni ester akrilne kiseline (Spoj 250), N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-metilsulfanil-propionamid (Spoj 251), N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-metansulfonil-propionamid (Spoj 252), {3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-amid etansulfonske kiseline (Spoj 253), N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-4-metoksi-benzensulfonamid (Spoj 254), N-5-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil-sulfamoil}-4-metil-tiazol-2-il)-acetamid (Spoj 255), 5-acetil-2-klor-N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-benzensulfonamid (Spoj 256), {3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-amid naftalen-2-sulfonske kiseline (Spoj 257), N-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-C-fenil-metansulfonamid (Spoj 258), 2-(3-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-ureido)-etilni ester 2-metil-akrilne kiseline (Spoj 259), 1-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-(2-hidroksi-etil)-urea (Spoj 260), etilni ester (3-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-ureido)-octene kiseline (Spoj 261), 1-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-(3-metoksi-fenil)-urea (Spoj 262), 1-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-(3-trifluormetil-fenil)-urea (Spoj 263), 1-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-propil-urea (Spoj 264), etilni ester 3-(3-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-ureido)-propionske kiseline (Spoj 265), 1-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-cikloheksil-urea (Spoj 266), 1-alil-3-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-urea (Spoj 267), 1-benzil-3-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-urea (Spoj 268), 1-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-etil-urea (Spoj 269), 1-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-fenil-urea (Spoj 270), 1-butil-3-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-urea (Spoj 271), 1-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-fenetil-urea (Spoj 272), metilni ester 2-(3-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-ureido)-benzojeve kiseline (Spoj 273), 1-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-(3-cijano-fenil)-urea (Spoj 274), 1-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-izopropil-urea (Spoj 275), 1-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-(4-metoksi-fenil)-urea (Spoj 276), benzilni ester {3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-karbaminske kiseline (Spoj 277), alil ester {3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-karbaminske kiseline (Spoj 278), etilni ester {3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-karbaminske kiseline (Spoj 279), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-[5-(3-hidroksi-butilamino)-2-metil-fenil]-metanon (Spoj 281), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-(3'-hidroksimetil-4-metil-bifenil-3-il)-metanon (Spoj 282), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-(3'-hidroksi-4-metil-bifenil-3-il)-metanon (Spoj 283), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-(4'-metoksi-4-metil-bifenil-3-il)-metanon (Spoj 284), N-{3'-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-bifenil-3-il}-acetamid (Spoj 285), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-(4-metil-3'-trifluormetoksi-bifenil-3-il)-metanon (Spoj 286), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-(3',4',5'-trifluor-4-metil-bifenil-3-il)-metanon (Spoj 288), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-(3',4'-dimetoksi-4-metil-bifenil-3-il)-metanon (Spoj 289), 3'-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4'-metil-bifenil-3-karbonitril (Spoj 290), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2-hidroksi-etil)-4-metil-benzensulfonamid (Spoj 291), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-N-(2-morfolin-4-il-etil)-benzensulfonamid (Spoj 292), N-alil-3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzensulfonamid (Spoj 293), N-(2-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzensulfonilamino}-etil)-acetamid (Spoj 294), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-N-propil-benzensulfonamid (Spoj 295), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2,3-dihidroksi-propil)-4-metil-benzensulfonamid (Spoj 296), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2-metoksi-etil)-4-metil-benzensulfonamid (Spoj 297), [4-(2,4-difluor-fenilamino)-2-nitro-fenil]-[5-(4-metoksi-benziloksi)-2-metil-fenil]-metanon (Spoj 306), [4-(2,4-difluor-fenilamino)-2-nitro-fenil]-[5-(3-hidroksi-propoksi)-2-metil-fenil]-metanon (Spoj 307), [2-amino-4-(2,4-difluor-fenilamino)-fenil]-[5-(3-hidroksi-propoksi)-2-metil-fenil]-metanon (Spoj 308), [4-(2,4-difluor-fenilamino)-2-nitro-fenil]-[2-metil-5-(2-morfolin-4-il-etoksi)-fenil]-metanon (Spoj 309), [2-amino-4-(2,4-difluor-fenilamino)-fenil]-[2-metil-5-(2-morfolin-4-il-etoksi)-fenil]-metanon (Spoj 310), [4-(2,4-difluor-fenilamino)-2-nitro-fenil]-[5-(2,2-dimetil-[1,3]dioksolan-4-ilmetoksi)-2-metil-fenil]-metanon (Spoj 311), [4-(2,4-difluor-fenilamino)-2-nitro-fenil]-[5-(2,3-dihidroksi-propoksi)-2-metil-fenil]-metanon (Spoj 312), [2-amino-4-(2,4-difluor-fenilamino)-fenil]-[5-(2,3-dihidroksi-propoksi)-2-metil-fenil]-metanon (Spoj 313), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-[2-fluor-5-(3-hidroksi-propoksi)-fenil]-metanon (Spoj 314), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-[5-(2,2-dimetil-[1,3]dioksolan-4-ilmetoksi)-2-fluor-fenil]-metanon (Spoj 315), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-[5-(2,3-dihidroksi-propoksi)-2-fluor-fenil]-metanon (Spoj 316), [2-klor-4-(2,6-difluor-fenilamino)-fenil]-[2-klor-5-(2-morfolin-4-il-etoksi)-fenil]-metanon (Spoj 328), (±)-[2-klor-4-(2,6-difluor-fenilamino)-fenil]-[2-klor-5-(2,3-dihidroksi-propoksi)-fenil]-metanon (Spoj 329), [5-(3-brom-propoksi)-2-klor-fenil]-[2-klor-4-(2,6-difluor-fenilamino)-fenil]-metanon (Spoj 330), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-(5-hidroksimetil-2-metil-fenil)-metanon (Spoj 331), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-(5-klormetil-2-metil-fenil)-metanon (Spoj 332), [5-azidometil-2-metil-fenil]-[2-klor-4-(2,4-difluor-fenilamino)-fenil]-metanon (Spoj 333), [5-aminometil-2-metil-fenil]-[2-klor-4-(2,4-difluor-fenilamino)-fenil]-metanon (Spoj 334), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-(5-hidroksimetil-2-metoksi-fenil)-metanon (Spoj 335), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metoksi-benzilni ester octene kiseline (Spoj 336), N-tert-butoksi-3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metoksi-benzamid (Spoj 337), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-metoksi-4-metil-benzamid (Spoj 338), N-butoksi-3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzamid (Spoj 339), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-cikloheksilmetoksi-4-metil-benzamid (Spoj 340), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-N-(2-metil-tiazol-4-ilmetoksi)-benzamid (Spoj 341), N-benziloksi-3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzamid (Spoj 342), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(4-metoksi-benziloksi)-4-metil-benzamid (Spoj 343), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzojeva kiselina N',N'-dimetil-hidrazid (Spoj 344), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-N-morfolin-4-il-benzamid (Spoj 345), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-hidroksi-4-metil-benzamid (Spoj 346), 4-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(2-hidroksi-etil)-3-metil-benzamid (Spoj 347), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-[5-(3-hidroksi-propenil)-2-metil-fenil]-metanon (Spoj 348), metilni ester 4-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzoilamino}-tiofen-3-karboksilne kiseline (Spoj 349), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-furan-2-ilmetil-4-metil-benzamid (Spoj 350), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-(3-metoksi-fenil)-4-metil-benzamid (Spoj 351), metilni ester 2-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzoilamino}-benzojeve kiseline (Spoj 352), metilni ester 3-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzoilamino}-tiofen-2-karboksilne kiseline (Spoj 353), 4-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzoilamino}-tiofen-3-karboksilna kiselina (Spoj 354), 2-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzoilamino}-benzojeva kiselina (Spoj 355), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-N-[2-(2-hidroksi-etilkarbamoil)-fenil]-4-metil-benzamid (Spoj 356), (2-hidroksi-etil)-amid 3-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzoilamino}-tiofen-2-karboksilne kiseline (Spoj 357), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-(5-etinil-2-metil-fenil)-metanon (Spoj 362), hidrazid 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzojeve kiseline (Spoj 364), 1-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzoil}-4-etil-3-tio semikarbazid (Spoj 365), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-[5-(5-etilamino-[1,3,4]tiadiazol-2-il)-2-metil-fenil]-metanon (Spoj 366), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-[2-metil-5-(1H-tetrazol-5-il)-fenil]-metanon (Spoj 367), etilni ester 3-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-fenil}-3-okso-propionske kiseline (Spoj 368), [2-klor-4-(2,4-difluor-fenilamino)-fenil]-[5-(4,5-dihidro-oksazol-2-il)-2-metil-fenil]-metanon (Spoj 369), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzojeva kiselina (Spoj 424), 2-{3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metil-benzoilamino}-etilni ester 2-metil-akrilne kiseline (Spoj 425), 3-[2-klor-4-(4-klor-2-fluor-fenilamino)-benzoil]-4-metil-benzojeva kiselina (Spoj 432), 3-[2-klor-4-(2,4-difluor-fenilamino)-benzoil]-4-metoksi-benzojeva kiselina (Spoj 437), 3-[2-klor-4-(2,6-difluor-fenilamino)-benzoil]-4-metoksi-benzojeva kiselina (Spoj 443),
26. Farmaceutska smjesa, naznačena time što obuhvaća spoj prema bilo kojem od zahtjeva 1-25 ili njegovu farmaceutski prihvatljivu sol ili ester zajedno s farmaceutski prihvatljivim nosačem ili pomoćnom tvari.
27. Smjesa prema zahtjevu 26, naznačena time što dalje obuhvaća drugu djelatnu tvar izabranu iz skupine koja obuhvaća glukokortikoide, analoge vitamina D, antihistaminike, antagoniste faktora aktivacije trombocita (PAF), antikolinergike, metil ksantine, ß-adrenergike, inhibitore COX-2, salicilate, indometacin, flufenamat, naproksen, timegadin, soli zlata, penicilamin, sredstva za snižavanje kolesterola u serumu, retionide, soli cinka i salicilazosulfapiridin.
28. Spoj prema bilo kojem od zahtjeva 1-25, naznačen time što je za uporabu kao lijek.
29. Spoj prema bilo kojem od zahtjeva 1-25, naznačen time što je za uporabu kao sredstvo protiv upale ili protiv raka.
30. Spoj prema bilo kojem od zahtjeva 1-25, naznačen time što je za uporabu kod prevencije, liječenja ili poboljšanja oftalmoloških bolesti ili stanja.
31. Uporaba spoja prema bilo kojem od zahtjeva 1-25, naznačena time što se radi o proizvodnji lijeka za profilaksu, liječenje ili poboljšanje upalnih bolesti ili stanja, ili oftalmoloških bolesti ili stanja.
32. Uporaba spoja prema bilo kojem od zahtjeva 1-25, naznačena time što se radi o proizvodnji lijeka za liječenje ili poboljšanje raka.
33. Uporaba prema zahtjevu 31, naznačena time što je lijek namijenjen za primjenu zajedno s drugom djelatnom tvari tvar izabranom iz skupine koja obuhvaća glukokortikoide, analoge vitamina D, antihistaminike, antagoniste faktora aktivacije trombocita (PAF), antikolinergike, metil ksantine, ß-adrenergike, inhibitore COX-2, salicilate, indometacin, flufenamat, naproksen, timegadin, soli zlata, penicilamin, sredstva za snižavanje kolesterola u serumu, retionide, soli cinka i salicilazosulfapiridin.
34. Uporaba prema zahtjevu 31 ili 33, naznačena time što je upalna bolest ili stanje astma, alergija, artritis, reumatoidni artritis, spondiloartritis, giht, ateroskleroza, kronična upalna bolest crijeva, Chronova bolest, neurološke upale, upalne bolesti oka, proliferativni i upalni poremećaji kože, psorijaza, atopijski dermatitis, akne, uveitis, sepsa, septički šok ili akne, osteoporoza.
35. Uporaba prema zahtjevu 31, naznačena time što je oftalmološka bolest akutna makularna degeneracija ili makularna degeneracija povezana sa starenjem.
36. Postupak proizvodnje spoja općenite strukture I, [image] gdje su R1, R2, R3, R4, R5 i R6 kako je određeno u zahtjevu 1, naznačen time što obuhvaća korake a) pretvaranje spoja općenite strukture VI, [image] gdje Hal predstavlja halogen, a R5 i R6 su kako je određeno u zahtjevu 1, od kojih je svaki nezavisno od drugog zaštićen ili nezaštićen, u organometalni međuprodukt; b) transmetaliranje organometalnog međuprodukta u organocinkov međuprodukt; c) spajanje organocinkovog međuprodukta s kiselinskim halidom općenite strukture V, [image] gdje je R2 kako je određeno u zahtjevu 1, zaštićen ili nezaštićen, u prisutnosti katalizatora radi dobivanja spoja općenite strukture IV, [image] gdje su R1, R2, R5 i R6 kako je određeno gore, od kojih je svaki nezavisno od drugog zaštićen ili nezaštićen; d) po izboru, pretvaranje, stavljanje ili uklanjanje zaštite jednog ili više supstituenata ili funkcionalnih skupina R1, R2, R5 i R6 spoja općenite strukture IV, radi dobivanja drugog spoja općenite strukture IV; e) reduciranje spoja općenite strukture IV iz koraka c) ili d) do amina općenite strukture III, [image] gdje su R1, R2, R5 i R6 kako je određeno gore, od kojih je svaki nezavisno od drugog zaštićen ili nezaštićen; f) po izboru, pretvaranje, stavljanje ili uklanjanje zaštite jednog ili više supstituenata ili funkcionalnih skupina R1, R2, R5 i R6 spoja općenite strukture III, radi dobvanja drugog spoja općenite strukture III; g) spajanje amina općenite strukture III iz koraka e) ili f) sa spojem općenite strukture II, [image] gdje je L triflat (trifluormetansulfonat) ili halogen, R3 i R4 su kako je određeno u zahtjevu 1, od kojih je svaki nezavisno od drugog zaštićen ili nezaštićen, radi dobivanja spoja opće strukture I, pri čemu su R1, R2, R3, R4, R5 i R6 kako je određeno gore, od kojih je svaki nezavisno od drugog zaštićen ili nezaštićen; h) po izboru, pretvaranje, stavljanje ili uklanjanje zaštite jednog ili više supstituenata ili funkcionalnih skupina R1, R2, R3, R4, R5 ili R6 spoja općenite strukture I iz koraka g) radi dobivanja drugog spoja općenite strukture I.
37. Postupak proizvodnje spoja općenite strukture I, [image] gdje su R1, R2, R3, R4, R5 i R6 kako je određeno u zahtjevu 1, naznačen time što obuhvaća korake a) pretvaranje spoja općenite strukture VIIa, [image] gdje Hal predstavlja halogen, W je halogen ili triflat (trifluormetansulfonat), a R2 je kako je određen u zahtjevu 1, zaštićeni ili nezaštićeni, u organometalni međuprodukt; b) transmetaliranje organometalnog međuprodukta u organocinkov međuprodukt; c) spajanje organocinkovog međuprodukta s kiselinskim halidom općenite strukture VIII, [image] gdje su R1, R5 i R6 kako je određeno u zahtjevu 1, od kojih je svaki nezavisno od drugoga zaštićen ili nezaštićen, u prisutnosti katalizatora radi dobivanja spoja općenite strukture IIIa, [image] gdje su W, R1, R2, R5 i R6 kako je određeno gore, od kojih je svaki nezavisno od drugog zaštićen ili nezaštićen; d) po izboru, pretvaranje, stavljanje ili uklanjanje zaštite jednog ili više supstituenata ili funkcionalnih skupina W, R1, R2, R5 i R6 spoja općenite strukture IIIa, radi dobivanja drugog spoja općenite strukture IIIa; e) spajanje spoja općenite strukture IIIa iz koraka c) ili d) s aminom općenite strukture IIa, [image] gdje su R3 i R4 kako je određeno u zahtjevu 1, od kojih je svaki nezavisno od drugog zaštićen ili nezaštićen, radi dobivanja spoja općenite strukture I, gdje su R1, R2, R3, R4, R5 i R6 kako je određeno gore, od kojih je svaki nezavisno od drugog zaštićen ili nezaštićen ; f) po izboru, pretvaranje, stavljanje ili uklanjanje zaštite jednog ili više supstituenata ili funkcionalnih skupina R1, R2, R3, R4, R5 ili R6 spoja općenite strukture I iz koraka e) radi dobvanja drugog spoja općenite strukture I.
38. Postupak prema zahtjevu 36 ili 37, naznačen time što se spajanje u koraku c) provodi u prisutnosti soli bakra.
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JP4939216B2 (ja) 2012-05-23
IS8323A (is) 2006-02-23
CA2530302C (en) 2013-12-03
US20060166990A1 (en) 2006-07-27
ES2346972T3 (es) 2010-10-22
CN1826310B (zh) 2010-07-21
ZA200510137B (en) 2007-04-25
MXPA06000708A (es) 2006-04-19
AR045082A1 (es) 2005-10-12
TW200509892A (en) 2005-03-16
ATE469878T1 (de) 2010-06-15
AU2004259264A1 (en) 2005-02-03
HK1090350A1 (en) 2006-12-22
RU2006105639A (ru) 2006-06-10
DK1658263T3 (da) 2010-09-27

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