HRP20120250T1 - Derivati 5-fenil-pentanoične kiseline kao inhibitori matriks metaloproteinaze za liječenje astme i drugih bolesti - Google Patents

Derivati 5-fenil-pentanoične kiseline kao inhibitori matriks metaloproteinaze za liječenje astme i drugih bolesti Download PDF

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HRP20120250T1
HRP20120250T1 HR20120250T HRP20120250T HRP20120250T1 HR P20120250 T1 HRP20120250 T1 HR P20120250T1 HR 20120250 T HR20120250 T HR 20120250T HR P20120250 T HRP20120250 T HR P20120250T HR P20120250 T1 HRP20120250 T1 HR P20120250T1
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Croatia
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compound
ethyl
hydroxy
pentanoic acid
formula
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HR20120250T
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P. Palle Venkata
Jitendra Sattigeri Viswajanani
Kumar Khera Manoj
Rao Voleti Sreedhara
Ray Abhijit
G. Dastidar Sunanda
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Ranbaxy Laboratories Limited
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Application filed by Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Publication of HRP20120250T1 publication Critical patent/HRP20120250T1/hr

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Abstract

Spoj, naznačen time, da je to spoj: 5-Bifenil-4-il-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 1), 2-(2-{[(Benziloksi)karbonil]amino}etil)-5-bifenil-4-il-3-hidroksipentanoična kiselina (spoj br. 11), 5-Bifenil-4-il-3-hidroksi-2-{2-[(fenilacetil)amino]etil}pentanoična kiselina (spoj br. 45), 5-Bifenil-4-il-3-hidroksi-2-[2-(1-oksoftalazin-2(1H)-il)etil] pentanoična kiselina (spoj br. 47), 5-Bifenil-4-il-3-hidroksi-2-[2-(2'-oksospiro[ciklopropan-1,3'-indol]-1'(2'H)-il)etil] pentanoična kiselina (spoj br. 49), 3-Hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]-5-[4'-(trifluormetil)bifenil-4-il]pentanoična kiselina (spoj br. 59), 5-(3',4'-Difluorbifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 60), 3-Hidroksi-5-(4'-metoksibifenil-4-il)-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 64), 5-(4'-klorbifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3 (4H)-il)etil]pentanoična kiselina (spoj br. 65), 3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 67), 3-Hidroksi-5-(4'-metilbifenil-4-il)-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]pentanoična kiselina (spoj br. 68), 5-(4'-klorbifenil-4-il)-3-hidroksi-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]pentanoična kiselina (spoj br. 69), 3-Hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]-5-[4'-(trifluormetoksi)bifenil-4-il]pentanoična kiselina (spoj br. 70), 5-(4'-Fluorbifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 71), 3-hidroksi-5-(4'-metilbifenil-4-il)-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 72), 5-(4'-Cijanobifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 73), 5-(4'-Fluorbifenil-4-il)-3-hidroksi-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]pentanoična kiselina (spoj br. 74), 3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]pentanoična kiselina (spoj br. 75), 5-(4'-Etilbifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 76), 3-Hidroksi-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-5-[4'-(trifluormetil)bifenil-4-il]pentanoična kiselina (spoj br. 77), 5-Bifenil-4-il-3-hidroksi-2-[2-(-okso-4-fenil-4a,8a-dihidroftalazin-2(1 H)-il)etil] pentanoična kiselina (spoj br. 84), 5-Bifenil-4-il-3-hidroksi-2-[2-(3-okso-2,3-dihidro-4H-1,4-benzoksazin-4-il)etil] pentanoična kiselina (spoj br. 85), 5-Bifenil-4-il-2-{2-[(3aR,7aS)-1,3-diokso-1,3,3a,4,7,7a-heksahidro-2H-izoindol-2-il]etil}-3-hidroksipentanoična kiselina (spoj br. 86), 5-Bifenil-4-il-2-(2-([(4-fluorfenil)sulfonil]amino)etil)-3-hidroksipentanoična kiselina (spoj br. 87), 5-Bifenil-4-il-2-(2-{[(3-fluorfenil)acetil]amino}etil)-3-hidroksipenta

Claims (15)

1. Spoj, naznačen time, da je to spoj: 5-Bifenil-4-il-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 1), 2-(2-{[(Benziloksi)karbonil]amino}etil)-5-bifenil-4-il-3-hidroksipentanoična kiselina (spoj br. 11), 5-Bifenil-4-il-3-hidroksi-2-{2-[(fenilacetil)amino]etil}pentanoična kiselina (spoj br. 45), 5-Bifenil-4-il-3-hidroksi-2-[2-(1-oksoftalazin-2(1H)-il)etil] pentanoična kiselina (spoj br. 47), 5-Bifenil-4-il-3-hidroksi-2-[2-(2'-oksospiro[ciklopropan-1,3'-indol]-1'(2'H)-il)etil] pentanoična kiselina (spoj br. 49), 3-Hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]-5-[4'-(trifluormetil)bifenil-4-il]pentanoična kiselina (spoj br. 59), 5-(3',4'-Difluorbifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 60), 3-Hidroksi-5-(4'-metoksibifenil-4-il)-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 64), 5-(4'-klorbifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3 (4H)-il)etil]pentanoična kiselina (spoj br. 65), 3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 67), 3-Hidroksi-5-(4'-metilbifenil-4-il)-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]pentanoična kiselina (spoj br. 68), 5-(4'-klorbifenil-4-il)-3-hidroksi-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]pentanoična kiselina (spoj br. 69), 3-Hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]-5-[4'-(trifluormetoksi)bifenil-4-il]pentanoična kiselina (spoj br. 70), 5-(4'-Fluorbifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 71), 3-hidroksi-5-(4'-metilbifenil-4-il)-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 72), 5-(4'-Cijanobifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 73), 5-(4'-Fluorbifenil-4-il)-3-hidroksi-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]pentanoična kiselina (spoj br. 74), 3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]pentanoična kiselina (spoj br. 75), 5-(4'-Etilbifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 76), 3-Hidroksi-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-5-[4'-(trifluormetil)bifenil-4-il]pentanoična kiselina (spoj br. 77), 5-Bifenil-4-il-3-hidroksi-2-[2-(-okso-4-fenil-4a,8a-dihidroftalazin-2(1 H)-il)etil] pentanoična kiselina (spoj br. 84), 5-Bifenil-4-il-3-hidroksi-2-[2-(3-okso-2,3-dihidro-4H-1,4-benzoksazin-4-il)etil] pentanoična kiselina (spoj br. 85), 5-Bifenil-4-il-2-{2-[(3aR,7aS)-1,3-diokso-1,3,3a,4,7,7a-heksahidro-2H-izoindol-2-il]etil}-3-hidroksipentanoična kiselina (spoj br. 86), 5-Bifenil-4-il-2-(2-([(4-fluorfenil)sulfonil]amino)etil)-3-hidroksipentanoična kiselina (spoj br. 87), 5-Bifenil-4-il-2-(2-{[(3-fluorfenil)acetil]amino}etil)-3-hidroksipentanoična kiselina (spoj br. 88), 5-Bifenil-4-il-2-{2-[(4-fluorbenzoil)amino]etil}-3-hidroksipentanoična kiselina (spoj br. 89), 5-Bifenil-4-il-3-hidroksi-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]pentanoična kiselina (spoj br. 90), S-Bifenil-4-il-3-hidroksi-2-[2-(1 -okso-1,3-dihidro-2H-izoindol-2-il)etil] pentanoična kiselina (spoj br. 91), 5-Bifenil-4-il-2-[2-({([(4-fluorfenil)amino]karbonil}amino)etil]-3-hidroksipentanoična kiselina (spoj br. 92), 5-Bifenil-4-il-2-[2-(4,4-dimetil-2,6-dioksopiperidin-1-il)etil]-3-hidroksipentanoična kiselina (spoj br. 93), 5-Bifenil-4-il-2-[2-(7,9-diokso-8-azaspiro[4.5]dec-8-il)etil]-3-hidroksipentanoična kiselina (spoj br. 94), 5-Bifenil-4-il-3-hidroksi-2-[2-(2-okso-1,3-benzoksazol-3(2H)-il)etil]pentanoična kiselina (spoj br. 96), 2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]pentanoična kiselina (spoj br. 97), 5-Bifenil-4-il-2-[2-(5,6-diklor-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksipentanoična kiselina (spoj br. 102), 5-Bifenil-4-il-2-[2-(2,4-diokso-1,4-dihidrokinazolin-3(2H)-il)etil]-3-hidroksipentanoična kiselina (spoj br. 103), 5-Bifenil-4-il-2-[2-(1,3-diokso-1,3-dihidro-2H-pirolo[3,4-c]piridin-2-il)etil]-3-hidroksipentanoična kiselina (spoj br. 104), 2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-5-(3',4'-difluorbifenil-4-il)-3-hidroksipentanoična kiselina (spoj br. 105), (2R,3S+2S,3R)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-5-(4'-fluorbifenil-4-il)-3-hidroksipentanoična kiselina (spoj br. 106), (2R,3S+2S,3R)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksi-5-[4-(trifluormetil)bifenil-4-il] pentanoična kiselina (spoj br. 107), (2R,3R+2S,3S)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-5-(4'-fluorbifenil-4-il)-3-hidroksipentanoična kiselina (spoj br. 108), (2R,3R+2S,3S)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksi-5-[4'-(trifluormetil)bifenil-4-il]pentanoična kiselina (spoj br. 109), (2R,3R+2S, 3S)-2-[2-(5-te rt-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksi-5-(4'-metilbifenil-4-il)pentanoična kiselina (spoj br. 113), (2R,3S+2S,3R)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksi-5-(4'-metilbifenil-4-il)pentanoična kiselina (spoj br. 114), (2R,3R+2S,3S)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksi-5-(4'-metoksibifenil-4-il)pentanoična kiselina (spoj br. 115), (2R,3R+2S,3S)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-5-(4'-klorbifenil-4-il)-3-hidroksipentanoična kiselina (spoj br. 116), (2R,3S+2S,3R)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-5-(4’-klorbifenil-4-il)-3-hidroksipentanoična kiselina (spoj br. 117), (2R,3S+2S,3R)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksi-5-(4'-metoksibifenil-4-il)pentanoična kiselina (spoj br. 118), 5-Bifenil-4-il-2-[2-(5-tert-butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksipentanoična kiselina (spoj br. 121), 5-Bifenil-4-il-3-hidroksi-2-[2-(1-okso-1,3-dihidro-2H-izoindol-2-il)butil]pentanoična kiselina (spoj br. 124), (2R,3S)-3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 133), (2S,3R)-3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 134), (2R,3R)-3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 135), ili (2S,3S)- 3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 136); uključujući njihove racemate, enantiomere i dijastereomere ili farmaceutski prihvatljiva sol bilo kojeg od prethodno navedenih spojeva.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time, da je to spoj: 5-Bifenil-4-il-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 1), ili 2-(2-{[(Benziloksi)karbonil]amino}etil)-5-bifenil-4-il-3-hidroksipentanoičnakiselina (spoj br. 11); uključujući njihove racemate, enantiomere i dijastereomere ili farmaceutski prihvatljiva sol bilo kojeg od prethodno navedenih spojeva.
3. Spoj u skladu s patentnim zahtjevom 1, naznačen time, da je to spoj: 3-Hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]-5-[4'-(trifluormetil)bifenil-4-il]pentanoična kiselina (spoj br. 59), 5-(3',4'-Difluorbifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 60), 3-Hidroksi-5-(4'-metoksibifenil-4-il)-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 64), 5-(4'-klorbifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 65), 3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 67), 5-(4'-klorbifenil-4-il)-3-hidroksi-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]pentanoična kiselina (spoj br. 69), 3-Hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]-5-[4'-(trifluormetoksi)bifenil-4-il]pentanoična kiselina (spoj br. 70), 3-hidroksi-5-(4'-metilbifenil-4-il)-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 72), 3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]pentanoična kiselina (spoj br. 75), 5-(4'-Etilbifenil-4-il)-3-hidroksi-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil] pentanoična kiselina (spoj br. 76), 3-Hidroksi-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-5-[4'-(trifluormetil)bifenil-4-il]pentanoična kiselina (spoj br. 77), 5-Bifenil-4-il-3-hidroksi-2-[2-(5-metil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]pentanoična kiselina (spoj br. 90), 2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]pentanoična kiselina (spoj br. 97), 5-Bifenil-4-il-2-[2-(5,6-diklor-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksipentanoična kiselina (spoj br. 102), (2R,3S+2S,3R)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksi-5-[4’-(trifluormetil)bifenil-4-il] pentanoična kiselina (spoj br. 107), (2R,3R+2S,3S)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksi-5-[4-(trifluormetil)bifenil-4-il] pentanoična kiselina (spoj br. 109), (2R,3R+2S,3S)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksi-5-(4-metoksibifenil-4-il)pentanoična kiselina (spoj br. 115), (2R,3R+2S,3S)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-5-(4’-klorbifenil-4-il)-3-hidroksipentanoična kiselina (spoj br. 116), (2R,3S+2S,3R)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-5-(4’-klorbifenil-4-il)-3-hidroksipentanoična kiselina (spoj br. 117), (2R,3S+2S,3R)-2-[2-(5-tert-Butil-1,3-diokso-1,3-dihidro-2H-izoindol-2-il)etil]-3-hidroksi-5-(4-metoksibifenil-4-il)pentanoična kiselina (spoj br. 118), (2R,3S)-3-Hidroksi-S-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 133), (2S,3R)-3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 134) ili (25,3 S)-3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina (spoj br. 136); uključujući njihove racemate, enantiomere i dijastereomere ili farmaceutski prihvatljiva sol bilo kojeg od prethodno navedenih spojeva.
4. Spoj u skladu s patentnim zahtjevom 1, naznačen time, da je taj spoj 3-Hidroksi-5-[4-(6-metoksipiridin-3-il)fenil]-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina uključujući njezine racemate, enantiomere i dijastereomere ili njegove farmaceutski prihvatljive soli.
5. Spoj u skladu s patentnim zahtjevom 1, naznačen time, da je taj spoj (2S,3R)-3-Hidroksi-5-[4-(6- metoksipiridin-3-il)fenil]-2-[2-(4-okso-1,2,3-benzotriazin-3(4H)-il)etil]pentanoična kiselina ili njegove farmaceutski prihvatljive soli.
6. Farmaceutski pripravak, naznačen time, da sadrži terapijski učinkovitu količinu spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 5 u kombinaciji s farmaceutski prihvatljivim nosačem, ekscipijensom ili razrjeđivačem.
7. Farmaceutski pripravak u skladu s patentnim zahtjevom 6, naznačen time, da dodatno sadrži jednu ili više djelatnih tvari odabranih između sljedećeg: a. Protuupalna sredstva odabrana između sljedećeg: (i) nesteroidna protuupalna sredstva odabrana između piroksikama, diklofenaka, propionskih kiselina, fenamata, pirazolona, salicilata, inhibitora PDE-4/pd38 MAP kinaze/katepsina; (ii) leukotriena, inhibitora LTC4/LTD4/LTE4/LTB4, inhibitora 5-lipoksigenaze i antagonista receptora PAF; (iii) nhibitora Cox-2; (iv) inhibitora MMP; ili (v) inhibitora interleukina-I; b. Sredstva protiv hipertenzije odabrana između sljedećeg: (i) inhibitora ACE odabranih između enalaprila, lisinoprila, valsartana, telmisartana ili kvinaprila; (ii) antagonista i agonista receptora angiotenzina II odabranih između losartana, kandesartana, irbesartana, valsartana ili eprosartana, (iii) p-blokatora; ili (iv) blokatora kalcijevih kanala; ili c. imunosupresivnih sredstava odabranih između ciklosporina, azatioprina ili metotreksata; ili protuupalnih kortikosteroida.
8. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time, da se koristi u medicini.
9. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time, da se koristi za liječenje ili profilaksu životinje ili humanog subjekta koji pate od upalnih bolesti ili s njima povezane patologije.
10. Spoj u skladu s patentnim zahtjevom 9, naznačen time, da su upalne bolesti ili s njima povezana patologija astma, reumatoidni artritis, COPD, rinitis, osteoartritis, psorijatični artritis, psorijaza, plućna fibroza, upala pluća, akutni respiratorni distres sindrom, perodontitis, multipla skleroza, gingivitis, ateroskleroza, neointimalna proliferacija povezana s restenozom i ishemijskim zatajenjem srca, moždani udar, bolest bubrega ili metastaza tumora.
11. Postupak za pripremu spoja Formule VIII [image] naznačen time, da A" odabran je između (CH2)n-NR4R5, (CH2)n-NHC(=Y)R4, (CH2)n-NHC(=Y)NR5Rx, (CH2)n-NHC(=O)OR4, (CH2)n-NHSO2R4, (CH2)n-amidino ili (CH2)n-guanidino, n je cijeli broj u rasponu od 1 do 5, Y je kisik ili sumpor; R4 je alkil, alkenil, alkinil, cikloalkil, aril, heterociklil, heteroaril, aralkil, heteroarilalkil, heterociklilalkil ili cikloalkilalkil; R5 je vodik ili R4; R4 i R5 po izboru zajedno tvore heterociklički prsten koji sadrži jedan ili više heteroatoma koji su odabrani između O, N ili S; a Rx je R4 ili SO2N(R4)2; koji obuhvaća: a) reakciju spoja Formule II [image] u kojem hal je Cl, Br ili I; sa spojem Formule III [image] u kojem P je alkil ili aralkil koji su odabrani između terc-butila, etila, metila ili benzila; čime se dobiva spoj Formule IV; [image] b) reakciju spoja Formula IV sa spojem Formule V hal-A” Formula V u kojem hal je Cl, Br ili I, a A" je definiran gore, čime se dobiva spoj Formule VI; [image] c) redukciju spoja Formule VI, čime se dobiva spoj Formule VII; te [image] d) skidanje zaštite sa spoja Formule VII, čime se dobiva spoj Formule VIII [image]
12. Postupak za pripremu spoja Formule XXI [image] naznačen time, da obuhvaća: e) reakciju spoja Formule IX [image] sa spojem Formule III [image] čime se dobiva spoj Formule X; [image] f) reakciju spoja Formule X sa spojem Formule XI hal-(CH2)n-OP1 Formula XI čime se dobiva spoj Formule XII; [image] g) redukciju spoja Formule XII, čime se dobiva spoj Formule XIII; [image] h) reakciju spoja Formule XIII sa spojem Formule XIV P2-hal Formula XIV čime se dobiva spoj Formule XV; [image] j) konverziju spoja Formule XVI, čime se dobiva spoj Formule XVII [image] reakcijom sa spojem Formule L-hal (u kojem L je metansulfonil, p-toluenesulfonil, a hal je halogen); k) reakciju spoja Formule XVII sa spojem Formule M-A' ili A', čime se dobiva spoj Formule XVIII; [image] l) reakciju spoja Formule XVIII sa spojem Formule XIX [image] čime se dobiva spoj Formule XX; te [image] m) skidanje zaštite sa spoja Formule XX, čime se dobiva spoj Formule XXI [image] pri čemu: P je alkil ili aralkil odabran između tert-butila, etila ili metila te benzila; P1 je zaštitna sililna skupina odabrana između tert-butildimetilsilana, tert-butildifenilsilana ili triizopropilsilana; P2 je aralkil ili heterociklil odabran između benzila, 4-metoksibenzila ili 2,4,6-trimetoksibenzila ili tetrahidropiranila; hal ili halogen je Cl, Br ili I; LG je odlazeća skupina, primjerice mezil, tozil ili triflil ili halogen; A' je NR4R5, NHC(=Y)R4, NHC(=Y)NR5Rx, NHC(=O)OR4, NHSO2R4, amidino ili guanidino, a M je metal odabran između kalija, litija ili natrija; R7 je vodik, halogen (pri čemu je halogen vezan na R7 F, Cl, Br, I), hidroksi, -COOR4, alkil, alkenil, alkinil, cikloalkil, alkoksi, alkeniloksi, alkiniloksi, ariloksi, heterocikliloksi, heteroariloksi, cikloalkiloksi, acil, tioacil, cijano, nitro, amino, -CHO, -OCF3, -CF3, -SCF3, -NR4R5, -C(=Y)NR4R5, -NHC(=Y)R4, -NHC (=Y)NR5Rx, -NHC(=O)OR4, -NHSO2R4, (SO)mR4, aril, heterociklil, heteroaril, heterociklilalkil ili heteroarilalkil koji je po izboru dodatno supstituiran; R4 je alkil, alkenil, alkinil, cikloalkil, aril, heterociklil, heteroaril, aralkil, heteroarilalkil, heterociklilalkil ili cikloalkilalkil; m je cijeli broj u rasponu 0 - 2; n je cijeli broj u rasponu od 1 do 5; R5 je vodik ili R4; a Rx je R4 ili -SO2N(R4)2.
13. Postupak za pripremu spoja Formule XXV [image] naznačen time, da R4 predstavlja alkil, alkenil, alkinil, cikloalkil, aril, heterociklil, heteroaril, aralkil, heteroarilalkil, heterociklilalkil ili cikloalkilalkil; koji obuhvaća: n) reakciju spoja Formule IV [image] u kojem P je alkil ili aralkil odabran između terc-butila, etila ili metila te benzila; sa spojem Formule XXII [image] čime se dobiva spoj Formule XXIII; [image] o) redukciju spoja Formule XXIII, čime se dobiva spoj Formule XXIV; te [image] p) skidanje zaštite sa spoja Formule XXIV, čime se dobiva spoj Formule XXV [image]
14. Postupak za pripremu spoja Formule XXX [image] naznačen time, da RF predstavlja R4CO-, R4SO2- R4OCO- ili (R4)NH-C(=Y)-; koji obuhvaća: a) reakciju spoja Formule XXIV [image] sa spojem Formule XXVI Rt-COOH Formula XXVI čime se dobiva spoj Formule XXVII: pri čemu: P je alkil ili aralkil odabran između terc-butila, etila, metila ili benzila; Rt je alkil, aril, cikloalkil, aralkil, heterociklilalkil ili heteroarilalkil; a R4 je alkil, alkenil, alkinil, cikloalkil, aril, heterociklil, heteroaril, aralkil, heteroarilalkil, heterociklilalkil ili cikloalkilalkil; [image] b) skidanje zaštite sa spoja Formule XXVII, čime se dobiva spoj Formule XXVIII [image] pri čemu su P i Rt definirani jednako kao gore; c) derivaciju spoja Formule XXVIII sa spojem Formule RD, pri čemu: RD je R4COhal, halCOOR4, R4SO2hal ili (R4)N=C(=Y), a hal je Cl, Br ili I; te Y je kisik ili sumpor; čime se dobiva spoj Formule XXX [image] d) skidanje zaštite sa spoja Formule XXX, čime se dobiva spoj Formule XXX; te [image] e) skidanje zaštite sa spoja Formule XXX, čime se dobiva spoj Formule XXXI: [image]
15. Postupak odvajanja spoja Formule VIII, Formule XXI, Formule XXV ili Formule XXX ili spoja sukladno definicijama u bilo kojem prethodnom patentnom zahtjevu u dijastereomerske parove ili pojedinačne dijastereomere, naznačen time, da se provodi preparativnom tankoslojnom kromatografijom ili HPLC-om na kiralnoj ili akiralnoj koloni.
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