402958-95-6Relevant articles and documents
Azetidines and spiro azetidines as novel P2 units in hepatitis C virus NS3 protease inhibitors
Bondada, Lavanya,Rondla, Ramu,Pradere, Ugo,Liu, Peng,Li, Chengwei,Bobeck, Drew,McBrayer, Tamara,Tharnish, Philip,Courcambeck, Jerome,Halfon, Philippe,Whitaker, Tony,Amblard, Franck,Coats, Steven J.,Schinazi, Raymond F.
, p. 6325 - 6330 (2013/11/19)
Herein, we report the synthesis and structure-activity relationship studies of new analogs of boceprevir 1 and telaprevir 2. Introduction of azetidine and spiroazetidines as a P2 substituent that replaced the pyrrolidine moiety of 1 and 2 led to the disco
A PROCESS FOR THE PREPARATION OF SUBSTITUTED PROLYL PEPTIDES AND SIMILAR PEPTIDOMIMETICS
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, (2011/09/21)
The present invention relates to a process for the stereoselective preparation of a compound having the general formula (I) or its respective diastereomers: comprising reacting a compound having the general formula (II) or its diastereomers: with a compound of the general formula III: R3-COOH and a compound of the general formula IV: R4-NC wherein R1 represents each independently, or jointly a substituted or unsubstituted alkyl, alkenyl, alkynyl, aromatic or non-aromatic, mono-, di- or tricyclic, or heterocyclic structure, and R2 represents a hydrogen atom, a substituted or unsubstituted alkyl, alkenyl, alkynyl, aromatic or non-aromatic, mono-, di- or tricyclic, or heterocyclic structure, and R3 represents a substituted or unsubstituted alkyl, alkenyl, or alkynyl, or an aromatic or non-aromatic aromatic or non-aromatic, mono-, di- or tricyclic, or heterocyclic structure.
P4 and P1′ optimization of bicycloproline P2 bearing tetrapeptidyl α-ketoamides as HCV protease inhibitors
Yip, Yvonne,Victor, Frantz,Lamar, Jason,Johnson, Robert,Wang, Q. May,Glass, John I.,Yumibe, Nathan,Wakulchik, Mark,Munroe, John,Chen, Shu-Hui
, p. 5007 - 5011 (2007/10/03)
We describe herein the design, synthesis, and antiviral activity of a series of P4 modified tetrapeptidyl α-ketoamides as HCV protease inhibitors. The most promising analog identified through this SAR, 5a, 5c, and 5e demonstrated excellent enzyme inhibitory potency, enzyme selectivity, cellular activity, and acceptable therapeutic indexes. With the aim of improving HCV protease inhibitors reported in our previous manuscripts, we synthesized and evaluated a series of 1a-based tetrapeptidyl α-ketoamides with additional P4 modification. The promising analog discovered through this SAR, 5a, was further derivatized at P1′ or P1 position. As a result of these efforts, we found that replacement of the P4 valine as seen in 1a with cyclohexylglycine (Chg) resulted in the discovery of 5a, 5c, and 5e endowed with improved cellular activity in comparison to 1a.
