HRP20130166T1 - Supstituirani spojevi nikotinamida i njihova uporaba u farmaceutskim proizvodima - Google Patents

Supstituirani spojevi nikotinamida i njihova uporaba u farmaceutskim proizvodima Download PDF

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HRP20130166T1
HRP20130166T1 HRP20130166AT HRP20130166T HRP20130166T1 HR P20130166 T1 HRP20130166 T1 HR P20130166T1 HR P20130166A T HRP20130166A T HR P20130166AT HR P20130166 T HRP20130166 T HR P20130166T HR P20130166 T1 HRP20130166 T1 HR P20130166T1
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nicotinamide
ethylthio
phenylsulfonyl
thienylmethyl
alkyl
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HRP20130166AT
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Beatrix Merla
Sven KĂĽhnert
Robert Frank
Dagmar Kaulartz
Wolfgang Schröder
Gregor Bahrenberg
Klaus Schiene
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GrĂĽnenthal GmbH
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Pyridine Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Claims (14)

1. Supstituirani spojevi nikotinamida sa općom formulom I [image] naznačeni time da n = 0, 1 ili 2 p = 0 ili 1 q = 0 ili 1, R1 označava aril ili heteroaril, nesupstituiran ili monosupstituiran ili polisupstituiran; C1-6-alkil, C3-10-cikloalkil ili heterociklil, nesupstituiran ili monosupstituiran ili polisupstituiran; R2 označava H; C1-6-alkil, nesupstituiran ili monosupstituiran ili polisupstituiran; R3 označava aril ili heteroaril, nesupstituiran ili monosupstituiran ili polisupstituiran; C1-6-alkil ili C3-10-cikloalkil, u svakom slučaju nesupstituiran ili monosupstituiran ili polisupstituiran; R4, R5, R6 i R7 neovisno jedan od drugoga označavaju H; C1-6-alkil, nesupstituiran ili monosupstituiran ili polisupstituiran; R8, R9 i R10 neovisno jedan od drugoga označavaju H, F, Cl, Br, O-C1-6-alkil, CF3, OCF3, SCF3, C1-6-alkil; uz uvjet da kada R3 označava 3-trifluorometilfenil ili 4-trifluorometil-2-piridil, R2, R4 i R5 označavaju H i n označava 0, tada R1 ne označava 2-piridil ili 2-tienil i kada R3 označava fenil ili metil, R2, R4 i R5 označavaju H i n označava 0, tada R1 ne označava 2-tienil; pri čemu C1-6-alkil sadrži acikličke zasićene ili nezasićene radikale ugljikovodika i pri čemu cikloalkil i C3-10-cikloalkil sadrže zasićene ili nezasićene ali ne aromatske cikličke ugljikovodike; u obliku racemata; enantiomera, diastereoizomera, smjesa enantiomera ili diastereoizomera ili pojedinačnog enantiomera ili diastereoizomera; baza i/ili soli fiziološki prihvatljivih kiselina.
2. Supstituirani derivati nikotinamida prema zahtjevu 1, naznačeni time da "supstituirani alkil ", "supstituirani heterociklil" i " supstituirani cikloalkil " predstavlja zamjenu radikala vodika sa F, Cl, Br, I, -CN, NH2, NH-C1-6-alkilom, NH-C1-6-alkil-OH, C1-6-alkilom, N(C1-6-alkil)2, N(C1-6-alkil-OH)2, NO2, SH, S-C1-6-alkilom, S-benzilom, O-C1-6-alkilom, OH, O-C1-6-alkil-OH, =O, O-benzilom, C(=O)C1-6-alkilom, CO2H, CO2-C1-6-alkilom, fenil, fenoksi, morfolinilom, piperidinilom, pirolidinilom ili benzilom; te " supstituirani aril " i "supstituirani heteroaril" predstavlja zamjenu jednom ili više puta, npr. dva, tri ili četiri puta, jednog ili više atoma vodika iz prstenastog sustava sa F, Cl, Br, I, CN, NH2, NH-C1-6-alkilom, NH-C1-6-alkil-OH, N(C1-6-alkil)2, N(C1-6-alkil-OH)2, NO2, SH, S-C1-6-alkilom, OH, O-C1-6-alkilom, O-C1-6alkil-OH, C(=O)C1-6-alkilom, C(=O)NHC1-6-alkilom; o-piridilom; C(=O)-arilom; C(=O)-N-morfolinom; C(=O)-piperidinom; (C=O)-pirolidinom; (C=O)-piperazinom; NHSO2C1-6-alkilom, NHCOC1-6-alkilom, CO2H, CH2SO2-fenilom, CO2-C1-6-alkilom, OCF3, SCF3, CF3, [image] C1-6-alkilom, pirolidinilom, piperidinilom, morfolinilom, benziloksi, fenoksi, fenilom, piridilom, alkilarilom, imidazolilom, pirazolilom, tienilom ili furilom.
3. Supstituirani derivati nikotinamida prema bilo kojem zahtjevu 1 ili zahtjevu 2, naznačeni time da p i q označavaju 1.
4. Supstituirani derivati nikotinamida prema bilo kojem zahtjevu 1 ili zahtjevu 2, naznačeni time da R1 predstavlja tert-butil; fenil, piridil, tienil, furil ili cikloheksil, nesupstituiran ili monosupstituiran ili polisupstituiran.
5. Supstituirani derivati nikotinamida prema zahtjevu 4, naznačeni time da R1 predstavlja cikloheksil, ili fenil, nesupstituiran ili monosupstituiran ili polisupstituiran sa F, CH3, Cl, Br, CF3, OCH3, SCF3 ili OCF3; piridil, tienil ili furil, nesupstituiran ili monosupstituiran ili polisupstituiran sa CH3.
6. Supstituirani derivati nikotinamida prema bilo kojem zahtjevu 1 ili zahtjevu 2, naznačeni time da R2 predstavlja CH3 ili H, te naročito H.
7. Supstituirani derivati nikotinamida prema bilo kojem zahtjevu 1 ili zahtjevu 2, naznačeni time da R4, R5, R6 i R7 neovisno jedan od drugoga predstavljaju H ili CH3, te naročito H.
8. Supstituirani derivati nikotinamida prema bilo kojem zahtjevu 1 ili zahtjevu 2, naznačeni time da n označava 0 ili 1, te naročito poželjno 0.
9. Supstituirani derivati nikotinamida prema bilo kojem zahtjevu 1 ili zahtjevu 2, naznačeni time da R3 označava aril ili heteroaril, nesupstituiran ili monosupstituiran ili polisupstituiran, te poželjno R3 označava fenil nesupstituiran ili supstituiran sa CF3 ili CH3.
10. Supstituirani derivati nikotinamida prema zahtjevu 1 naznačeni time da su iz skupine koja sadrži: 1 2-(2-(fenilsulfonil)etiltio)-N-(piridin-2-ilmetil)nikotinamid 2 2-(2-(fenilsulfonil)etiltio)-N-(piridin-4-ilmetil)nikotinamid 3 N-(3-fluorofenetil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 4 N-metil-N-(3-metilbenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 5 N-(4-metilbenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 6 2-(2-(fenilsulfonil)etiltio)-N-(2-(trifluorometil)benzil)nikotinamid 7 2-(2-(fenilsulfonil)etiltio)-N-(piridin-3-ilmetil)nikotinamid 8 N-(3,5-difluorobenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 9 N-metil-N-fenetil-2-(2-(fenilsulfonil)etiltio)nikotinamid 10 N-(3-metoksibenzil)-N-metil-2-(2-(fenilsulfonil)etiltio)nikotinamid 11 N-(2-fluorobenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 12 N-(3,4-difluorobenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 13 N-(3-bromobenzil)-N-metil-2-(2-(fenilsulfonil)etiltio)nikotinamid 14 N-(2-metoksibenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 15 N-(3-fluorobenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 16 N-(furan-2-ilmetil)-N-metil-2-(2-(fenilsulfonil)etiltio)nikotinamid 17 N-(4-metoksibenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 18 N-(2-klorobenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 19 N-(3,4-diklorobenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 20 N-(4-fluorobenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 21 N-(2-metoksifenetil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 22 N-(2,6-difluorobenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 23 N-(2-metilbenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 24 N-(3,5-dimetoksibenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 25 N-(3-klorobenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 26 N-(2,4-diklorobenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 29 N-(4-klorobenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 30 N-(2,3-diklorobenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 31 N-(4-bromobenzil)-N-metil-2-(2-(fenilsulfonil)etiltio)nikotinamid 32 N-((1,3-dioksolan-2-il)metil)-N-metil-2-(2-(fenilsulfonil)etiltio)-nikotinamid 33 N-benzil-N-metil-2-(2-tosiletiltio)nikotinamid 34 N-(piridin-2-ilmetil)-2-(2-tosiletiltio)nikotinamid 35 N-(piridin-4-ilmetil)-2-(2-tosiletiltio)nikotinamid 36 N-(tiofen-2-ilmetil)-2-(2-tosiletiltio)nikotinamid 37 N-(3-fluorofenetil)-2-(2-tosiletiltio)nikotinamid 38 N-metil-N-(3-metilbenzil)-2-(2-tosiletiltio)nikotinamid 39 N-(furan-2-ilmetil)-2-(2-tosiletiltio)nikotinamid 40 N-(piridin-3-ilmetil)-2-(2-tosiletiltio)nikotinamid 41 N-(3,5-difluorobenzil)-2-(2-tosiletiltio)nikotinamid 42 N-(3-metoksibenzil)-N-metil-2-(2-tosiletiltio)nikotinamid 43 N-(2-fluorobenzil)-2-(2-tosiletiltio)nikotinamid 44 N-(3-metilbenzil)-2-(2-tosiletiltio)nikotinamid 45 N-(3,4-difluorobenzil)-2-(2-tosiletiltio)nikotinamid 46 N-(3-bromobenzil)-N-metil-2-(2-tosiletiltio)nikotinamid 47 N-(4-metoksibenzil)-2-(2-tosiletiltio)nikotinamid 48 N-(2-klorobenzil)-2-(2-tosiletiltio)nikotinamid 49 N-(4-fluorobenzil)-2-(2-tosiletiltio)nikotinamid 50 N-(3,5-dimetoksibenzil)-2-(2-tosiletiltio)nikotinamid 51 N-(3-klorobenzil)-2-(2-tosiletiltio)nikotinamid 52 2-(2-tosiletiltio)-N-(3-(trifluorometil)benzil)nikotinamid 54 N-benzil-2-(2-(fenilsulfonil)etiltio)nikotinamid 55 N-benzil-N-metil-2-(2-(fenilsulfonil)etiltio)nikotinamid 56 N-(cikloheksilmetil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 57 2-(2-(fenilsulfonil)etiltio)-N-(1-(3-(trifluorometil)fenil)etil)-nikotinamid 58 N-(2-cikloheksiletil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 59 2-(2-(cikloheksiltio)etiltio)-N-(tiofen-2-ilmetil)nikotinamid 60 N-(neopentil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 61 N-(5-metilfuran-2-ilmetil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 62 N-(furan-2-ilmetil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 63 2-(2-(fenilsulfonil)etiltio)-N-(tetrahidro-2H-piran-4-ilmetil)-nikotinamid 64 2-(2-(fenilsulfonil)etiltio)-N-(4-(trifluorometiltio)benzil)nikotinamid 65 2-(2-(fenilsulfonil)etiltio)-N-(3-tolilmetil)nikotinamid 66 (R)-N-(1-cikloheksiletil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 67 N-(1-(3,4-dimetilfenil)etil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 68 N-(1-tiofen-2-iletil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 69 N-(1-(3,5-dimetilfenil)metil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 70 N-(cikloheksilmetil)-2-(2-(3-trifluorometilfenilsulfonil)etiltio)-nikotinamid 71 (S)-N-(1-cikloheksiletil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 72 N-(1-(3,5-dimetilfenil)etil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 73 N-(tiofen-2-ilmetil)-2-(2-(3-(trifluorometil)feniltio)etiltio)-nikotinamid 74 N-(ciklopentilmetil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 75 N-(ciklobutilmetil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 76 N-((1,4-dioksan-2-il)metil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 77 2-(2-(fenilsulfonil)etiltio)-N-(4-(piridin-2-iloksi)benzil)nikotinamid 78 N-(2-metilbutil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 79 N-(2-etilbutil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 80 N-(ciklopropilmetil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 81 N-(3-(2-metoksietoksi)propil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 82 2-(2-(fenilsulfonil)etiltio)-N-(1-(4-(trifluorometiltio)fenil)etil)-nikotinamid 83 N-(3-(1H-pirazol-1-il)benzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 84 N-((2,3-dihidrobenzofuran-5-il)metil)-2-(2-(fenilsulfonil)etiltio)-nikotinamid 85 N-(4-fenoksibenzil)-2-(2-(fenilsulfonil)etiltio)nikotinamid 86 N-(((1R,2S,5R)-6,6-dimetilbiciklo[3.1.1]heptan-2-il)metil)-2-(2-(fenil-sulfonil)etiltio)nikotinamid 87 N-(tiofen-2-ilmetil)-2-(2-(3-(trifluorometil)fenilsulfonil)etiltio)-nikotinamid 88 2-(2-(fenilsulfonil)etiltio)-N-(3-(trifluorometil)benzil)nikotinamid 93 N-izobutil-2-(2-(fenilsulfonil)etiltio)nikotinamid 94 2-[2-(benzensulfonil)etiltio]-N-(2-tetrahidropiranilmetil)-nikotinamid 95 2-[2-(benzensulfonil)etiltio]-N-[(5-metil-2-tienil)metil]-nikotinamid 96 2-[2-(benzensulfonil)etiltio]-N-[(4-metil-2-tienil)metil]-nikotinamid 97 N-(1-adamantilmetil)-2-[2-(benzensulfonil)etiltio]-nikotinamid 98 2-[2-(benzensulfonil)etiltio]-N-[(3-morfolinofenil)metil]-nikotinamid 99 2-[2-(4-klorofenil)sulfoniletiltio]-N-(2-tienilmetil)-nikotinamid 100 2-[2-(4-fluorofenil)sulfoniletiltio]-N-(2-tienilmetil)-nikotinamid 101 N-(2-tienilmetil)-2-[2-[3-(trifluorometoksi)fenil]sulfoniletiltio]-nikotinamid 102 N-(2-tienilmetil)-2-[2-[4-(trifluorometil)fenil]sulfoniletiltio]-nikotinamid 103 N-(2-tienilmetil)-2-[2-[4-(trifluorometoksi)fenil]sulfoniletiltio]-nikotinamid 104 2-[2-(m-tolilsulfonil)etiltio]-N-(2-tienilmetil)-nikotinamid 105 2-[2-(m-toliltio)etiltio]-N-(2-tienilmetil)-nikotinamid 106 2-[2-(3-fluorofenil)sulfoniletiltio]-N-(2-tienilmetil)-nikotinamid 107 2-[2-(benzensulfonil)etiltio]-N-(3,3-dimetilbutil)-nikotinamid 108 2-[2-(benzensulfonil)etiltio]-N-(2-benzotiofenilmetil)-nikotinamid 109 2-[2-(feniltio)etiltio]-N-(2-tienilmetil)-nikotinamid 110 2-[2-(benzensulfinil)etiltio]-N-(2-tienilmetil)-nikotinamid 111 2-(2-cikloheksilsulfoniletiltio)-N-(2-tienilmetil)-nikotinamid 112 N-(2-tienilmetil)-2-[2-[[2-(trifluorometil)fenil]tio]etiltio]-nikotinamid 113 N-(2-tienilmetil)-2-[2-[2-(trifluorometil)fenil]sulfiniletiltio]-nikotinamid 114 N-(2-tienilmetil)-2-[2-[2-(trifluorometil)fenil]sulfoniletiltio]-nikotinamid 115 2-[2-(benzensulfonil)etiltio]-N-[(5-kloro-2-tienil)metil]-nikotinamid 116 2-[2-(2-fluorofenil)sulfoniletiltio]-N-(2-tienilmetil)-nikotinamid 117 2-[2-[3,5-bis(trifluorometil)fenil]sulfoniletiltio]-N-(2-tienilmetil)-nikotinamid 118 2-[2-(3-metoksifenil)sulfoniletiltio]-N-(2-tienilmetil)-nikotinamid 119 2-[2-(4-metoksifenil)sulfoniletiltio]-N-(2-tienilmetil)-nikotinamid 120 2-[2-(benzensulfonil)etiltio]-N-(4-tetrahidrotiopiranilmetil)-nikotinamid 121 2-[2-(4-etilfenil)sulfoniletiltio]-N-(2-tienilmetil)-nikotinamid 122 N-(2-tienilmetil)-2-[2-[[4-(trifluorometil)fenil]tio]etiltio]-nikotinamid 123 2-[2-(o-toliltio)etiltio]-N-(2-tienilmetil)-nikotinamid 124 2-[2-[(3-fluorofenil)tio]etiltio]-N-(2-tienilmetil)-nikotinamid 125 2-[2-[(3,4-difluorofenil)tio]etiltio]-N-(2-tienilmetil)-nikotinamid 126 2-[2-[(2,4-difluorofenil)tio]etiltio]-N-(2-tienilmetil)-nikotinamid 127 2-[2-(benzensulfonil)etiltio]-N-[2-(2-tienil)etil]-nikotinamid 128 2-[2-(benzensulfonil)etiltio]-N-fenetil-nikotinamid 129 2-[2-(benzensulfonil)etiltio]-N-(3-fenilpropil)-nikotinamid 130 2-[2-(3,4-difluorofenil)sulfoniletiltio]-N-(2-tienilmetil)-nikotinamid 131 2-[2-(2,4-difluorofenil)sulfoniletiltio]-N-(2-tienilmetil)-nikotinamid 132 2-[2-[(2-fluorofenil)tio]etiltio]-N-(2-tienilmetil)-nikotinamid 133 2-[2-[(4-fluorofenil)tio]etiltio]-N-(2-tienilmetil)-nikotinamid 134 2-[2-[(4-klorofenil)tio]etiltio]-N-(2-tienilmetil)-nikotinamid 135 2-[2-(p-toliltio)etiltio]-N-(2-tienilmetil)-nikotinamid 136 2-[2-(benzensulfonil)etiltio]-N-izopentil-nikotinamid 137 2-[2-(benzensulfonil)etiltio]-N-(2-ciklopropiletil)-nikotinamid 138 2-[2-(benzensulfonil)etiltio]-N-(2-ciklopentiletil)-nikotinamid 139 N-(3,3-dimetilbutil)-2-[2-[3-(trifluorometil)fenil]sulfoniletiltio]-nikotinamid 140 N-(ciklopentilmetil)-2-[2-[3-(trifluorometil)fenil]sulfoniletiltio]-nikotinamid 141 2-[2-(benzensulfonil)etiltio]-6-metil-N-(2-tienilmetil)-nikotinamid 142 2-[2-(benzensulfonil)etiltio]-N-(2-tienilmetil)-6-(trifluorometil)-nikotinamid 143 2-[2-(benzensulfonil)etiltio]-6-fluoro-N-(2-tienilmetil)-nikotinamid 144 2-[2-(benzensulfonil)etiltio]-N-[(3-metilcikloheksil)metil]-nikotinamid 145 2-[2-(benzensulfonil)etiltio]-N-(cikloheptilmetil)-nikotinamid 146 2-[2-(benzensulfonil)etiltio]-N-[(2-metilcikloheksil)metil]-nikotinamid 147 2-[2-(benzensulfonil)etiltio]-N-[(4-metilcikloheksil)metil]-nikotinamid 148 2-[2-(benzensulfonil)etiltio]-5-fluoro-N-(2-tienilmetil)-nikotinamid 149 2-[2-(benzensulfonil)etiltio]-5-metil-N-(2-tienilmetil)-nikotinamid 150 2-[2-(benzensulfonil)etiltio]-N-(2-tienilmetil)-5-(trifluorometil)-nikotinamid.
11. Lijek koji sadrži barem jedan supstituirani spoj nikotinamida sa općom formulom I prema zahtjevu 1, naznačen time da n = 0, 1 ili 2 p = 0 ili 1 q = 0 ili 1, R1 označava aril ili heteroaril, nesupstituiran ili monosupstituiran ili polisupstituiran; C1-6-alkil, C3-10-cikloalkil ili heterociklil, nesupstituiran ili monosupstituiran ili polisupstituiran; R2 označava H; C1-6-alkil, nesupstituiran ili monosupstituiran ili polisupstituiran; R3 označava aril ili heteroaril, nesupstituiran ili monosupstituiran ili polisupstituiran; C1-6-alkil ili C3-10-cikloalkil, u svakom slučaju nesupstituiran ili monosupstituiran ili polisupstituiran; R4, R5, R6 i R7 neovisno jedan od drugoga označavaju H; C1-6-alkil, nesupstituiran ili monosupstituiran ili polisupstituiran; R8, R9 i R10 neovisno jedan od drugoga označavaju H, F, Cl, Br, O-C1-6-alkil, CF3, OCF3, SCF3, C1-6-alkil; u obliku racemata; enantiomera, diastereoizomera, smjesa enantiomera ili diastereoizomera ili pojedinačnog enantiomera ili diastereoizomera; baza i/ili soli fiziološki prihvatljivih kiselina, te proizvoljno jednu ili više farmaceutski prihvatljivih pomoćnih tvari.
12. Lijek prema zahtjevu 11 naznačen time da je iz skupine koja sadrži 89 2-(2-(fenilsulfonil)etiltio)-N-(tiofen-2-ilmetil)nikotinamid 90 N-(piridin-2-ilmetil)-2-(2-(3-(trifluorometil)fenilsulfonil)etiltio)-nikotinamid 91 N-(piridin-2-ilmetil)-2-(2-(5-(trifluorometil)piridin-2-ilsulfonil)etiltio)-nikotinamid 92 N-(tiofen-2-ilmetil)-2-(2-(5-(trifluorometil)piridin-2-ilsulfonil)etil-tio)nikotinamid.
13. Uporaba supstituiranih spojeva nikotinamida prema zahtjevu 1 ili 11 naznačena time da je za pripravu lijeka za liječenje boli, poželjno boli odabrane iz skupine koja sadrži akutnu bol, kroničnu bol, neuropatsku bol, bol u mišićima i bol uslijed upale.
14. Uporaba spojeva prema zahtjevu 1 ili 11 naznačena time da je za pripravu lijeka za liječenje epilepsije, migrene, anksioznih stanja i urinarne inkontinencije.
HRP20130166AT 2007-09-17 2013-02-27 Supstituirani spojevi nikotinamida i njihova uporaba u farmaceutskim proizvodima HRP20130166T1 (hr)

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