Reference

Preparation of macrocyclic inhibitors of hepatitis C virus

All Rights Reserved. Preparation of macrocyclic inhibitors of hepatitis C virus. De Kock, Herman Augustinus; Raboisson, Pierre Jean-Marie Bernard; Simmen, Kenneth Alan; Lindstroem, Mats Stefan; Kahnberg, Pia Cecilia; Antonov, Dmitry; Nilsson, Karl Magnus; Samuelsson, Bengt Bertil; Rosenquist, Aasa Annica Kristina (Tibotec Pharmaceuticals Ltd.; Medivir AB, Ire.). PCT Int. Appl. WO 2007014918 A1 8 Feb 2007, 85pp. DESIGNATED STATES: W: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LV, LY, MA, MD, MG, MK, MN, MW, MX, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC; RW: AT, BE, BF, BJ, CF, CG, CH, CI, CM, CY, DE, DK, ES, FI, FR, GA, GB, GR, IE, IS, IT, LU, MC, ML, MR, NE, NL, PT, SE, SN, TD, TG, TR. (English). (World Intellectual Property Organization). CODEN: PIXXD2. 154350-29-5 which is the cas registry number is also used here. APPLICATION: WO 2006-EP64812 28 Jul 2006. PRIORITY: EP 2005-107066 29 Jul 2005; EP 2006-101278 3 Feb 2006. DOCUMENT TYPE: Patent CA Section: 34 (Amino Acids, Peptides, and Proteins) Section cross-reference(s): 1, 7, 63 The invention relates to HCV inhibitory macrocyclic compds. I [the dashed line represents an optional double bond; R1, R2 are H or alkyl; n is 3-6], including N-oxides, salts, and stereoisomers, pharmaceutical compns. contg. them and processes for their prepn. Bioavailable combinations of the inhibitors I with ritonavir are also provided. Thus, macrocyclic peptide II was prepd. via etherification, peptide coupling, N-alkylation, and metathesis reactions and assayed for inhibition of HCV NS3/4A protease (EC50 = 7.0 x 10-3 mM, Ki = 0.12 nM). .