Patent ES-2613766-T3 (ES)
Title: Derivados de carbamato de hexadecahidrociclopropa(e)pirrolo(1,2-a)(1,4)diazaciclopentadecinilo sustituidos con 9-metilo como inhibidores de la proteasa no estructural 3 (NS3) para el tratamiento de infecciones del virus de la hepatitis C
Inventor: SUN LI-QIANG
IPC: A61K38/55
Filed: 2012-10-19
Granted: 2017-05-25
Abstract: Un compuesto seleccionado de: ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-14a-(((1-(fluorometil)ciclopropil)sulfonil)carbamoil)-2-((3-(4-isopropoxifenil)-6-metoxiisoquinolin-1-il)oxi)-7,9-dimetil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de (S)-3- (trifluorometil)tetrahidro-2H-piran-3-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-14a-(((1-(fluorometil)ciclopropil)sulfonil)carbamoil)-2-((3-(4-isopropoxifenil)-6- metoxiisoquinolin-1-il)oxi)-7,9-dimetil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a- hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de (R)-3- (trifluorometil)tetrahidro-2H-piran-3-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-2-((7-fluoro-6-metoxiisoquinolin-1-il)oxi)-14a-(((1- (fluorometil)ciclopropil)sulfonil)carbamoil)-7,9-dimetil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan-2-ilo; ((2R,6S,7R,9S,13aS,14aR,16aS,Z)-2-((7-fluoro-6-metoxiisoquinolin-1-il)oxi)-14a-(((1- (fluorometil)ciclopropil)sulfonil)carbamoil)-7,9-dimetil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan 2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-7-etil-2-((7-fluoro-3,6-dimetoxiisoquinolin-1-il)oxi)-9-metil-14a-(((1- metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan 2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-7-etil-2-((7-fluoro-3,6-dimetoxiisoquinolin-1-il)oxi)-9-metil-14a-(((1- metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 3,3-difluoro-2-metilbutan-2- ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-7-etil-2-((7-fluoro-3,6-dimetoxiisoquinolin-1-il)oxi)-9-metil-14a-(((1- metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 3-(trifluorometil)tetrahidro 2H-piran-3-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-2-((7-fluoro-6-metoxiisoquinolin-1-il)oxi)-14a-(((1- (fluorometil)ciclopropil)sulfonil)carbamoil)-7,9-dimetil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 2-(trifluorometil)tetrahidro- 2H-piran-2-ilo; ((2R,6S,7R,9S,13aS,14aR,16aS,Z)-2-((7-fluoro-6-metoxiisoquinolin-1-il)oxi)-14a-(((1- (fluorometil)ciclopropil)sulfonil)carbamoil)-7,9-dimetil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 2-(trifluorometil)tetrahidro 2H-piran-2-ilo; ((2R,6S,7R,9R,13a,14aR,16aS,Z)-7-etil-2-((7-fluoro-6-metoxiisoquinolin-1-il)oxi)-9-metil-14a-(((1- metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 2-(trifluorometil)tetrahidro 2H-piran-2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-2-((3,6-dimetoxiisoquinolin-1-il)oxi)-7-etil-14a-(((1- (fluorometil)ciclopropil)sulfonil)carbamoil)-9-metil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan 2-ilo; ((2R,6S,7R,9S,13aS,14aR,16aS,Z)-2-((3,6-dimetoxiisoquinolin-1-il)oxi)-7-etil-14a-(((1- (fluorometil)ciclopropil)sulfonil)carbamoil)-9-metil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a- hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan 2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-14a-((ciclopropilsulfonil)carbamoil)-7-etil-2-((8-fluoro-9-metoxi-2,3-dihidro-1H pirano[2,3-c]isoquinolin-6-il)oxi)-9-metil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan- 2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-2-((8-fluoro-9-metoxi-2,3-dihidro-1H-pirano[2,3-c]isoquinolin-6-il)oxi)-7,9- dimetil-14a-(((1-metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan 2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-7-etil-2-((8-fluoro-9-metoxi-2,3-dihidro-1H-pirano[2,3-c]isoquinolin-6-il)oxi)-9- metil-14a-(((1-metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan 2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-7-etil-2-((8-fluoro-9-metoxi-2,3-dihidro-1H-pirano[2,3-c]isoquinolin-6-il)oxi)-9- metil-14a-(((1-metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 3,3-difluoro-2-metilbutan-2- ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-7-etil-2-((6-fluoro-2,7-dimetoxiquinolin-4-il)oxi)-9-metil-14a-(((1- metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan-2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-7-etil-2-((6-fluoro-2,7-dimetoxiquinolin-4-il)oxi)-9-metil-14a-(((1- metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 3,3-difluoro-2-metilbutan-2- ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-14a-((ciclopropilsulfonil)carbamoil)-7-etil-2-((6-fluoro-2,7-dimetoxiquinolin-4- il)oxi)-9-metil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahidrociclopropa[e]pirrolo[1,2- a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan-2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-14a-((ciclopropilsulfonil)carbamoil)-7-etil-2-((6-fluoro-2,7-dimetoxiquinolin-4- il)oxi)-9-metil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahidrociclopropa[e]pirrolo[1,2- 15 a][1,4]diazaciclopentadecin-6-il)carbamato de 3,3-difluoro-2-metilbutan-2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-2-((6-fluoro-2,7-dimetoxiquinolin-4-il)oxi)-7,9-dimetil-14a-(((1- metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan 2-ilo; 20 ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-2-((6-fluoro-2,7-dimetoxiquinolin-4-il)oxi)-7,9-dimetil-14a-(((1- metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 3,3-difluoro-2-metilbutan-2- ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-14a-((ciclopropilsulfonil)carbamoil)-2-((6-metoxiisoquinolin-1-il)oxi)-7,9-dimetil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahidrociclopropa[e]pirrolo[1,2- a][1,4]diazaciclopentadecin-6-il)carbamato de terc-butilo; ((2R,6S,7R,9S,13aS,14aR,16aS,Z)-14a-((ciclopropilsulfonil)carbamoil)-2-((6-metoxiisoquinolin-1-il)oxi)-7,9- dimetil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahidrociclopropa[e]pirrolo[1,2- a][1,4]diazaciclopentadecin-6-il)carbamato de terc-butilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-2-((7-cloro-4-metoxiisoquinolin-1-il)oxi)-14a-((ciclopropilsulfonil)carbamoil)- 7,9-dimetil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahidrociclopropa[e]pirrolo[1,2- a][1,4]diazaciclopentadecin-6-il)carbamato de terc-butilo; ((2R,6S,7R,9S,13aS,14aR,16aS,Z)-2-((7-cloro-4-metoxiisoquinolin-1-il)oxi)-14a-((ciclopropilsulfonil)carbamoil)- 7,9-dimetil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahidrociclopropa[e]pirrolo[1,2- 35 a][1,4]diazaciclopentadecin-6-il)carbamato de terc-butilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-2-((2,7-dimetoxiquinolin-4-il)oxi)-7-etil-9-metil-14a-(((1- metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan 2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-2-((2,7-dimetoxiquinolin-4-il)oxi)-7-etil-9-metil-14a-(((1- metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 3,3-difluoro-2-metilbutan-2- ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-14a-((ciclopropilsulfonil)carbamoil)-2-((2,7-dimetoxiquinolin-4-il)oxi)-7-etil-9- metil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahidrociclopropa[e]pirrolo[1,2- a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan-2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-14a-((ciclopropilsulfonil)carbamoil)-2-((2,7-dimetoxiquinolin-4-il)oxi)-7-etil-9- metil-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahidrociclopropa[e]pirrolo[1,2- a][1,4]diazaciclopentadecin-6-il)carbamato de 3,3-difluoro-2-metilbutan-2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-2-((2,7-dimetoxiquinolin-4-il)oxi)-7,9-dimetil-14a-(((1- metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 1,1,1-trifluoro-2-metilpropan 2-ilo; ((2R,6S,7R,9R,13aS,14aR,16aS,Z)-2-((2,7-dimetoxiquinolin-4-il)oxi)-7,9-dimetil-14a-(((1- 55 metilciclopropil)sulfonil)carbamoil)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a hexadecahidrociclopropa[e]pirrolo[1,2-a][1,4]diazaciclopentadecin-6-il)carbamato de 3,3-difluoro-2-metilbutan-2- ilo;