公开(公告)号：US20060014779A1

公开(公告)日：2006-01-19

申请号：US10532657

申请日：2003-10-24

Applicant: Serge Boulet ,  Ann Filla ,  Peter Gallagher ,  Kevin Hudziak ,  Anette Johansson ,  Rushad Karanjawla ,  John Masters ,  Victor Matassa ,  Brian Mathes ,  Richard Rathmell ,  Maria Whatton ,  Chad Wolfe

Inventor： Serge Boulet ,  Ann Filla ,  Peter Gallagher ,  Kevin Hudziak ,  Anette Johansson ,  Rushad Karanjawla ,  John Masters ,  Victor Matassa ,  Brian Mathes ,  Richard Rathmell ,  Maria Whatton ,  Chad Wolfe

IPC: A61K31/4745 ,  A61K31/4743 ,  A61K31/4704 ,  A61K31/428 ,  A61K31/423

CPC classification number: C07C217/20 ,  C07C217/34 ,  C07D333/54

Abstract: There is provided a compound of formula (I) wherein A is selected from —O— and —S—; X is selected from C2-C8 alkyl, C2-C8 alkenyl, C3-C8 cycloalkyl and C4-C8 cycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n— where n is 0, 1 or 2, —CF3, —CN and —CONH2; Y is selected from phenyl, naphthyl, dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, thienopyridyl, indanyl, 1,3-benzodioxolyl, benzothienyl, indolyl and benzofuranyl, each of which may be optionally substituted with up to 4 or, where possible, 5 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n— where n is 0, 1 or 2, nitro, acetyl, —CF3, —SCF3 and cyano; and when Y is indolyl it may be substituted or further substituted by an N-substituent selected from C1-C4 alkyl; Z is selected from H, OR3 or F, wherein R3 is selected from H, C1-C6 alkyl and phenyl C1-C6 alkyl; R1 and R2 are each independently H or C1-C4 alkyl; with the proviso that, when Z is H, then Y may not be optionally substituted phenyl or optionally substituted naphthyl.

公开(公告)号：US06867284B1

公开(公告)日：2005-03-15

申请号：US09719261

申请日：1999-06-09

Applicant: Victor Matassa ,  Frank Narjes ,  Konrad Forster Koehler ,  Jesus Ontoria ,  Marco Poma ,  Antonella Marchetti

Inventor： Victor Matassa ,  Frank Narjes ,  Konrad Forster Koehler ,  Jesus Ontoria ,  Marco Poma ,  Antonella Marchetti

IPC: A61K38/00 ,  A61K31/335 ,  A61K31/38 ,  A61K31/405 ,  A61P31/12 ,  A61P43/00 ,  C07C229/22 ,  C07C237/22 ,  C07C271/22 ,  C07C311/51 ,  C07C323/60 ,  C07K5/06 ,  C07K5/08 ,  C07K7/06 ,  A61K38/04 ,  C07K5/00 ,  C07K7/00 ,  C07K16/00 ,  C07K17/00

CPC classification number: C07K7/06 ,  A61K38/00 ,  C07C229/22 ,  C07C237/22 ,  C07C271/22 ,  C07C311/51 ,  C07C323/60 ,  C07C2601/08 ,  C07C2601/14 ,  C07K5/06191 ,  C07K5/0827

Abstract: Fluorinated oligopeptides, especially those having 4,4-difluoro-2-amino butyric acid at the C terminus, may be effective inhibitors of hepatitis C virus NS3 protease. Examples of hexapeptides of the invention, optimized for binding in the S1 specificity pocket of the enzyme, may display IC50s at the sub-micromolar level. Embodiments of tripeptides of the invention, having a keto-acid group at the C-terminus are, likewise, potent inhibitors of NS3 protease.

Abstract translation: 氟化寡肽，特别是在C末端具有4,4-二氟-2-氨基丁酸的那些，可能是丙型肝炎病毒NS3蛋白酶的有效抑制剂。 针对酶的S1特异性袋中的结合进行了优化的本发明的六肽的实例可以显示亚微摩尔浓度的IC 50。 在C末端具有酮酸基团的本发明的三肽的实施方案同样是NS3蛋白酶的有效抑制剂。