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    Hepatitis C inhibitor peptides
    4.
    发明授权
    Hepatitis C inhibitor peptides 有权
    丙型肝炎抑制肽

    公开(公告)号：US06767991B1

    公开(公告)日：2004-07-27

    申请号：US09368670

    申请日：1999-08-05

    申请人： Montse Llinas-Brunet ,  Murray D. Bailey ,  Dale Cameron ,  Elise Ghiro ,  Nathalie Goudreau ,  Marc-André Poupart ,  Jean Rancourt ,  Youla S. Tsantrizos ,  Bruno Simoneau ,  Dominik M. Wernic

    发明人： Montse Llinas-Brunet ,  Murray D. Bailey ,  Dale Cameron ,  Elise Ghiro ,  Nathalie Goudreau ,  Marc-André Poupart ,  Jean Rancourt ,  Youla S. Tsantrizos ,  Bruno Simoneau ,  Dominik M. Wernic

    IPC分类号： C07K700

    CPC分类号： C07K7/06 ,  A61K38/00 ,  C07K5/06139 ,  C07K5/0808 ,  C07K5/101 ,  C07K5/1016 ,  C07K7/08 ,  C07K14/005 ,  C12N2770/24222

    摘要： Disclosed herein are hepatitis C viral protease inhibitors of formula (I): wherein a is 0 or 1; b is 0 or 1; Y is H or C1-6 alkyl; B is H, an acyl derivative or a sulfonyl derivative; R6, when present, is C1-6 alkyl substituted with carboxyl; R5, when present, is C1-6 alkyl optionally substituted with carboxyl; R4 is C1-10 alkyl, C3-7 cycloalkyl or C4-10 (alkylcycloalkyl); R3 is C1-10 alkyl optionally substituted with carboxyl, C3-7 cycloalkyl or C4-10 (alkylcycloalkyl); R2 is CH2—R20, NH—R20, O—R20 or S—R20; wherein R20 is a saturated or unsaturated C3-7 cycloalkyl or C4-10 (alkyl cycloalkyl) being optionally mono-, di- or tri-substituted with R21, or R20 is a C6 or C10aryl, C7-16 aralkyl, Het or (lower alkyl)-Het, all optionally mono-, di- or tri-substituted with R21, wherein R21 is as defined herein; R1 is C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, all optionally substituted with halogen; and W is hydroxy or a N-substituted amino: or W taken together with the carbonyl group to which it is bonded represents an ester group, or a pharmaceutically acceptable salt thereof.

    摘要翻译： 本文公开了式（I）的丙型肝炎病毒蛋白酶抑制剂：其中a为0或1; b为0或1; Y是H或C 1-6烷基; B是H，酰基衍生物或磺酰基衍生物;当存在时，R 6是被羧基取代的C 1-6烷基;当存在时，R 5是任选被羧基取代的C 1-6烷基; R4是C1-10烷基，C3-7环烷基或C4-10（烷基环烷基）; R3是任选被羧基取代的C1-10烷基，C3-7环烷基或C4-10（烷基环烷基）; R2是CH2-R20，NH- R20，O-R20或S-R20; 其中R 20是饱和或不饱和的C 3-7环烷基或任选被R 21单取代，二或三取代的C 4-10（烷基环烷基），或R 20是C 6或C 10芳基，C 7-16芳烷基，Het或（低级烷基 ）-Het，全部任选被R 21单取代，二取代或三取代，其中R 21如本文所定义; R 1是C 1-6烷基，C 2-6烯基或C 2-6炔基，全部被卤素取代; 和W是羟基或N-取代的氨基：或W与其键合的羰基一起代表酯基或其药学上可接受的盐。

    Hepatitis C inhibitor tri-peptides
    5.
    再颁专利
    Hepatitis C inhibitor tri-peptides 有权
    丙型肝炎抑制剂三肽

    公开(公告)号：USRE42164E1

    公开(公告)日：2011-02-22

    申请号：US12119609

    申请日：2008-05-13

    申请人： Montse Llinas-Brunet ,  Murray D. Bailey ,  Dale R. Cameron ,  Elise Ghiro ,  Nathalie Goudreau ,  Marc-Andre Poupart ,  Jean Rancourt ,  Youla S. Tsantrizos ,  Anne-Marie Faucher ,  Teddy Halmos ,  Dominik M. Wernic

    发明人： Montse Llinas-Brunet ,  Murray D. Bailey ,  Dale R. Cameron ,  Elise Ghiro ,  Nathalie Goudreau ,  Marc-Andre Poupart ,  Jean Rancourt ,  Youla S. Tsantrizos ,  Anne-Marie Faucher ,  Teddy Halmos ,  Dominik M. Wernic

    IPC分类号： A61K31/40 ,  A61K31/47 ,  C07D215/16 ,  C07D207/12

    CPC分类号： C12P13/02 ,  A61K38/21 ,  A61K45/06 ,  C07D207/16 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07K5/0806 ,  C07K5/0808 ,  C07K5/081 ,  C07K5/0812 ,  C12P41/005 ,  A61K2300/00

    摘要： Racemates, diastereoisomers and optical isomers of a compound of formula (I): wherein B is H, a C6 or C10 aryl, C7-16 aralkyl; Het or (lower alkyl)-Het, all of which optionally substituted with C1-6 alkyl; C1-6 alkoxy; C1-6 alkanoyl; hydroxy; hydroxyalkyl; halo; haloalkyl; nitro; cyano; cyanoalkyl; amino optionally substituted with C1-6 alkyl; amido; or (lower alkyl)amide; or B is an acyl derivative of formula R4—C(O)—; a carboxyl of formula R4—O—C(O)—; an amide of formula R4—N(R5)—C(O)—; a thioamide of formula R4—N(R5)—C(S)—; or a sulfonyl of formula R4—SO2; R5 is H or C1-6 alkyl; and Y is H or C1-6 alkyl; R3 is C1-8 alkyl, C3-7 cycloalkyl, or C4-10 alkylcycloalkyl, all optionally substituted with hydroxy, C1-6 alkoxy, C1-6 thioalkyl, amido, (lower alkyl)amido, C6 or C10 aryl, or C7-16 aralkyl; R2 is CH2—R20, NH—R20, O—R20 or S—R20, wherein R20 is a saturated or unsaturated C3-7 cycloalkyl or C4-10 (alkylcycloalkyl), all of which being optionally mono-, di- or tri-substituted with R21, or R20 is a C6 or C10 aryl or C7-14 aralkyl optionally substituted, or R20 is Het or (lower alkyl)-Het, both optionally substituted, Het or (lower alkyl)-Het; carboxyl; carboxy(lower alkyl); C6 or C10 aryl, C7-14 aralkyl or Het, said aryl, aralkyl or Het being optionally substituted; and R1 is H; C1-6 alkyl, C3-7 cycloalkyl, C2-6 alkenyl, or C2-6 alkynyl, all optionally substituted with halogen; or a pharmaceutically acceptable salt or ester thereof.

    摘要翻译： 式（I）化合物的外消旋体，非对映异构体和光学异构体：其中B是H，C6或C10芳基，C7-16芳烷基; Het或（低级烷基）-Het，其全部任选被C 1-6烷基取代; C 1-6烷氧基 C 1-6烷酰基; 羟基; 羟烷基 光环; 卤代烷基 硝基 氰基; 氰基烷基; 任选被C 1-6烷基取代的氨基; 氨基酸 或（低级烷基）酰胺; 或B是式R4-C（O） - 的酰基衍生物; 式R4-O-C（O） - 的羧基; 式R 4 -N（R 5）-C（O） - 的酰胺; 式R 4 -N（R 5）-C（S） - 的硫代酰胺; 或式R4-SO2的磺酰基; R5是H或C1-6烷基; Y为H或C 1-6烷基; R 3是C 1-8烷基，C 3-7环烷基或C 4-10烷基环烷基，全部任选被羟基，C 1-6烷氧基，C 1-6硫烷基，酰氨基，（低级烷基）酰氨基，C 6或C 10芳基或C 7〜 16芳烷基; R2是CH2-R20，NH-R20，O-R20或S-R20，其中R20是饱和或不饱和的C3-7环烷基或C4-10（烷基环烷基），它们都是任选的单 - ，二 - 或三 - 或R 20为任选取代的C 6或C 10芳基或C 7-14芳烷基，或R 20为Het或（低级烷基）-Het，均为任选取代的Het或（低级烷基）-Het; 羧基; 羧基（低级烷基）; C6或C10芳基，C7-14芳烷基或Het，所述芳基，芳烷基或Het任选被取代; 且R1为H; C 1-6烷基，C 3-7环烷基，C 2-6烯基或C 2-6炔基，全部被卤素取代; 或其药学上可接受的盐或酯。

    Hepatitis C inhibitor tri-peptides
    8.
    发明授权
    Hepatitis C inhibitor tri-peptides 有权
    丙型肝炎抑制剂三肽

    公开(公告)号：US06410531B1

    公开(公告)日：2002-06-25

    申请号：US09849057

    申请日：2001-05-04

    申请人： Montse Llinas-Brunet ,  Murray D. Bailey ,  Dale R. Cameron ,  Elise Ghiro ,  Nathalie Goudreau ,  Marc-Andre Poupart ,  Jean Rancourt ,  Youla S. Tsantrizos ,  Anne-Marie Faucher ,  Teddy Halmos ,  Dominik M. Wernic

    发明人： Montse Llinas-Brunet ,  Murray D. Bailey ,  Dale R. Cameron ,  Elise Ghiro ,  Nathalie Goudreau ,  Marc-Andre Poupart ,  Jean Rancourt ,  Youla S. Tsantrizos ,  Anne-Marie Faucher ,  Teddy Halmos ,  Dominik M. Wernic

    IPC分类号： A61K3535

    CPC分类号： C12P13/02 ,  A61K38/21 ,  A61K45/06 ,  C07D207/16 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07K5/0806 ,  C07K5/0808 ,  C07K5/081 ,  C07K5/0812 ,  C12P41/005 ,  A61K2300/00

    摘要： Racemates, diastereoisomers and optical isomers of a compound of formula (I): wherein B is H, a C6 or C10 aryl, C7-16 aralkyl; Het or (lower alkyl)-Het, all of which optionally substituted with C1-6 alkyl; C1-6 alkoxy; C1-6 alkanoyl; hydroxy; hydroxyalkyl; halo; haloalkyl; nitro; cyano; cyanoalkyl; amino optionally substituted with C1-6 alkyl; amido; or (lower alkyl)amide; or B is an acyl derivative of formula R4—C(O)—; a carboxyl of formula R4—O—C(O)—; an amide of formula R4—N(R5)—C(O)—; a thioamide of formula R4—N(R5)—C(S)—; or a sulfonyl of formula R4—SO2; R5 is H or C1-6 alkyl; and Y is H or C1-6 alkyl; R3 is C1-8 alkyl, C3-7 cycloalkyl, or C4-10 alkylcycloalkyl, all optionally substituted with hydroxy, C1-6 alkoxy, C1-6 thioalkyl, amido, (lower alkyl)amido, C6 or C10 aryl, or C7-16 aralkyl; R2 is CH2—R20, NH—R20, O—R20 or S—R20, wherein R20 is a saturated or unsaturated C3-7 cycloalkyl or C4-10 (alkylcycloalkyl), all of which being optionally mono-, di- or tri-substituted with R21, or R20 is a C6 or C10 aryl or C7-14 aralkyl optionally substituted, or R20 is Het or (lower alkyl)-Het, both optionally substituted, Het or (lower alkyl)-Het; carboxyl; carboxy(lower alkyl); C6 or C10 aryl, C7-14 aralkyl or Het, said aryl, aralkyl or Het being optionally substituted; and R1 is H; C1-6 alkyl, C3-7 cycloalkyl, C2-6 alkenyl, or C26 alkynyl, all optionally substituted with halogen; or a pharmaceutically acceptable salt or ester thereof.

    摘要翻译： 式（I）化合物的外消旋物，非对映异构体和光学异构体：其中B是H，C6或C10芳基，C7-16芳烷基; Het或（低级烷基）-Het，其全部任选被C 1-6烷基取代; C 1-6烷氧基 C 1-6烷酰基; 羟基; 羟烷基 光环; 卤代烷基 硝基 氰基; 氰基烷基 任选被C 1-6烷基取代的氨基; 氨基酸 或（低级烷基）酰胺; 或B是式R4-C（O） - 的酰基衍生物; 式R4-O-C（O） - 的羧基; 式R 4 -N（R 5）-C（O） - 的酰胺; 式R 4 -N（R 5）-C（S） - 的硫代酰胺; 或式R4-SO2的磺酰基; R5是H或C1-6烷基; 并且Y是H或C 1-6烷基; R 3是C 1-8烷基，C 3-7环烷基或C 4-10烷基环烷基，全部被羟基，C 1-6烷氧基，C 1-6硫烷基，酰氨基，（低级烷基） ，C6或C10芳基或C7-16芳烷基; R2是CH2-R20，NH-R20，O-R20或S-R20，其中R20是饱和或不饱和的C3-7环烷基或C4-10（烷基环烷基），全部 其任选被R 21单取代，二取代或三取代，或R 20为任选取代的C 6或C 10芳基或C 7-14芳烷基，或R 20为Het或（低级烷基）-Het，均为任选取代的Het或 （低级烷基）-Het; 羧基; 羧基（低级烷基）; C6或C10芳基，C7-14芳烷基或Het，所述芳基，芳烷基或Het任选被取代; 且R1为H; C 1-6烷基，C 3-7环烷基，C 2-6烯基或C 26炔基，全部被卤素取代; 或其药学上可接受的盐或酯。

    Hepatitis C inhibitor tri-peptides
    9.
    再颁专利
    Hepatitis C inhibitor tri-peptides 有权
    丙型肝炎抑制剂三肽

    公开(公告)号：USRE41894E1

    公开(公告)日：2010-10-26

    申请号：US12042627

    申请日：2008-03-05

    申请人： Montse Llinas-Brunet ,  Murray D. Bailey ,  Dale R. Cameron ,  Elise Ghiro ,  Nathalie Goudreau ,  Marc-Andre Poupart ,  Jean Rancourt ,  Youla S. Tsantrizos ,  Anne-Marie Faucher ,  Teddy Halmos ,  Dominik M. Wernic

    发明人： Montse Llinas-Brunet ,  Murray D. Bailey ,  Dale R. Cameron ,  Elise Ghiro ,  Nathalie Goudreau ,  Marc-Andre Poupart ,  Jean Rancourt ,  Youla S. Tsantrizos ,  Anne-Marie Faucher ,  Teddy Halmos ,  Dominik M. Wernic

    IPC分类号： A61K31/505 ,  A61K31/52 ,  C07D239/00 ,  C07D239/02 ,  C07D239/72

    CPC分类号： C12P13/02 ,  A61K38/21 ,  A61K45/06 ,  C07D207/16 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07K5/0806 ,  C07K5/0808 ,  C07K5/081 ,  C07K5/0812 ,  C12P41/005 ,  A61K2300/00

    摘要： Racemates, diastereoisomers and optical isomers of a compound of formula (I): wherein B is H, a C6 or C10 aryl, C7-16 aralkyl; Het or (lower alkyl)-Het, all of which optionally substituted with C1-6 alkyl; C1-6 alkoxy; C1-6 alkanoyl; hydroxy; hydroxy-alkyl; halo; haloalkyl; nitro; cyano; cyanoalkyl; amino optionally substituted with C1-6 alkyl; amido; or (lower alkyl)amide; or B is an acyl derivative of formula R4—C(O)—; a carboxyl of formula R4—O—C(O)—; an amide of formula R4—N(R5)—C(O)—; a thioamide of formula R4—N(R5)—C(S)—; or a sulfonyl of formula R4—SO2; R5 is H or C1-6 alkyl; and Y is H or C1-6 alkyl; R3 is C3-7 cycloalkyl, or C4-10 alkylcycloalkyl, all optionally substituted with hydroxy, C1-6 alkoxy, C1-6 thioalkyl, amido, (lower alkyl)amido, C6 or C10 aryl, or C7-16 aralkyl; R2 is CH2—R20, NH—R20, O—R20 or S—R20, wherein R20 is a saturated or unsaturated C3-7 cycloalkyl or C4-10 (alkylcycloalkyl), all of which being optionally mono-, di- or tri-substituted with R21, or R20 is a C6 or C10 aryl or C7-14 aralkyl optionally substituted, or R20 is Het or (lower alkyl)-Het, both optionally substituted, Het or (lower alkyl)-Het; carboxyl; carboxy(lower alkyl); C6 or C10 aryl, C7-14 aralkyl or Het, said aryl, aralkyl or Het being optionally substituted; and R1 is H; C1-6 alkyl, C3-7 cycloalkyl, C2-6 alkenyl, or C2-6 alkynyl, all optionally substituted with halogen; or a pharmaceutically acceptable salt or ester thereof.

    摘要翻译： 式（I）化合物的外消旋体，非对映异构体和光学异构体：其中B是H，C6或C10芳基，C7-16芳烷基; Het或（低级烷基）-Het，其全部任选被C 1-6烷基取代; C 1-6烷氧基 C 1-6烷酰基; 羟基; 羟基 - 烷基; 光环; 卤代烷基 硝基 氰基; 氰基烷基 任选被C 1-6烷基取代的氨基; 氨基酸 或（低级烷基）酰胺; 或B是式R4-C（O） - 的酰基衍生物; 式R4-O-C（O） - 的羧基; 式R 4 -N（R 5）-C（O） - 的酰胺; 式R 4 -N（R 5）-C（S） - 的硫代酰胺; 或式R4-SO2的磺酰基; R5是H或C1-6烷基; Y为H或C 1-6烷基; R 3为C 3-7环烷基或C 4-10烷基环烷基，全部任选被羟基取代，C 1-6烷氧基，C 1-6硫烷基，酰氨基，（低级烷基）酰氨基，C 6或C 10芳基或C 7-16芳烷基; R2是CH2-R20，NH-R20，O-R20或S-R20，其中R20是饱和或不饱和的C3-7环烷基或C4-10（烷基环烷基），它们都是任选的单 - ，二 - 或三 - 或R 20为任选取代的C 6或C 10芳基或C 7-14芳烷基，或R 20为Het或（低级烷基）-Het，均为任选取代的Het或（低级烷基）-Het; 羧基; 羧基（低级烷基）; C6或C10芳基，C7-14芳烷基或Het，所述芳基，芳烷基或Het任选被取代; 且R1为H; C 1-6烷基，C 3-7环烷基，C 2-6烯基或C 2-6炔基，全部被卤素取代; 或其药学上可接受的盐或酯。

    Hepatitis C inhibitor tri-peptides
    10.
    再颁专利
    Hepatitis C inhibitor tri-peptides 有权
    丙型肝炎抑制剂三肽

    公开(公告)号：USRE41356E1

    公开(公告)日：2010-05-25

    申请号：US12118926

    申请日：2008-05-12

    申请人： Montse Llinas-Brunet ,  Murray D. Bailey ,  Dale R. Cameron ,  Elise Ghiro ,  Nathalie Goudreau ,  Marc-Andre Poupart ,  Jean Rancourt ,  Youla S. Tsantrizos ,  Anne-Marie Faucher ,  Teddy Halmos ,  Dominik M. Wernic

    发明人： Montse Llinas-Brunet ,  Murray D. Bailey ,  Dale R. Cameron ,  Elise Ghiro ,  Nathalie Goudreau ,  Marc-Andre Poupart ,  Jean Rancourt ,  Youla S. Tsantrizos ,  Anne-Marie Faucher ,  Teddy Halmos ,  Dominik M. Wernic

    IPC分类号： A61K31/40 ,  C07D207/00 ,  C07D295/00

    CPC分类号： C12P13/02 ,  A61K38/21 ,  A61K45/06 ,  C07D207/16 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07K5/0806 ,  C07K5/0808 ,  C07K5/081 ,  C07K5/0812 ,  C12P41/005 ,  A61K2300/00

    摘要： Racemates, diastereolsomers and optical isomers of a compound of formula (I): wherein B is H, a C6 or C10 aryl, C7-16 aralkyl; Het or (lower alkyl)-Het, all of which optionally substituted with C1-6 alkyl; C1-6 alkoxy; C1-6 alkanoyl; hydroxy; hydroxyalkyl; halo; haloalkyl; nitro; cyano; cyanoalkyl; amino optionally substituted with C1-6 alkyl; amido; or (lower alkyl)amide; or B is an acyl derivative of formula R4—C(O)—; a carboxyl of formula R4—O—C(O)—; an amide of formula R4—N(R5)—C(O)—; a thioamide of formula R4—N(R5)—C(S)—; or a sulfonyl of formula R4—SO2; R5 is H or C1-6 alkyl; and Y is H or C1-6 alkyl; R3 is C1-8 alkyl, C3-7 cycloalkyl, or C4-10 alkylcycloalkyl, all optionally substituted with hydroxy, C1-6 alkoxy, C1-6 thioalkyl, amido, (lower alkyl)amido, C6 or C10 aryl, or C7-16 aralkyl; R2 is CH2—R20, NH—R20, O—R20 or S—R20, wherein R20 is a saturated or unsaturated C3-7 cycloalkyl or C4-10 (alkylcycloalkyl), all of which being optionally mono-, di- or tri-substituted with R21, or R20 is a C6 or C10 aryl or C7-14 aralkyl optionally substituted, or R20 is Het or (lower alkyl)-Het, both optionally substituted, Het or (lower alkyl)-Het; carboyl; carboxy(lower alkyl); C6 or C10 aryl, C7-14 aralkyl or Het, said aryl, aralkyl or Het being optionally substituted; and R1 is H; C1-6 alkyl, C3-7 cycloalkyl, C2-6 alkenyl, or C2-6 alkynyl, all optionally substituted with halogen; or a pharmaceutically acceptable salt or ester thereof.

    摘要翻译： 式（I）化合物的外消旋物，非对映异构体和光学异构体：其中B是H，C6或C10芳基，C7-16芳烷基; Het或（低级烷基）-Het，其全部任选被C 1-6烷基取代; C 1-6烷氧基; C 1-6烷酰基; 羟基; 羟烷基 光环; 卤代烷基 硝基 氰基; 氰基烷基 任选被C 1-6烷基取代的氨基; 氨基酸 或（低级烷基）酰胺; 或B是式R4-C（O） - 的酰基衍生物; 式R4-O-C（O） - 的羧基; 式R 4 -N（R 5）-C（O） - 的酰胺; 式R 4 -N（R 5）-C（S） - 的硫代酰胺; 或式R4-SO2的磺酰基; R5是H或C1-6烷基; Y为H或C 1-6烷基; R 3是C 1-8烷基，C 3-7环烷基或C 4-10烷基环烷基，全部任选被羟基，C 1-6烷氧基，C 1-6硫烷基，酰氨基，（低级烷基）酰氨基，C 6或C 10芳基或C 7〜 16芳烷基; R2是CH2-R20，NH-R20，O-R20或S-R20，其中R20是饱和或不饱和的C3-7环烷基或C4-10（烷基环烷基），它们都是任选的单 - ，二 - 或三 - 或R 20为任选取代的C 6或C 10芳基或C 7-14芳烷基，或R 20为Het或（低级烷基）-Het，均为任选取代的Het或（低级烷基）-Het; 羰基 羧基（低级烷基）; C6或C10芳基，C7-14芳烷基或Het，所述芳基，芳烷基或Het任选被取代; 且R1为H; C 1-6烷基，C 3-7环烷基，C 2-6烯基或C 2-6炔基，全部被卤素取代; 或其药学上可接受的盐或酯。