Reference

Preparation of amino acid 3-oxohexahydropyrrolo[3,2-b]pyrrol-4-yl amides as cysteine protease inhibitors

Kangasmetsa, Jussi; Hiscock, Stephen; Johnson, Tony; Samuelsson, Bertil; Tozer, Matt; Grabowska, Urszula (Medivir AB, Swed.). PCT Int. Appl. WO 2007006714 A1 18 Jan 2007, 137pp. 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. APPLICATION: WO 2006-EP63950 6 Jul 2006. PRIORITY: GB 2005-13841 7 Jul 2005. DOCUMENT TYPE: Patent CA Section: 34 (Amino Acids, Peptides, and Proteins) Section cross-reference(s): 1, 7, 63 The invention relates to amino acid amides, which have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases. Compds. of formula I [R1 is halo; R1' is H or halo; R2 is R4, COR4, O2CR4, sulfinyl or sulfonyl groups; R3 is H, OR4, or SR4; R3' is H; or CR3R3' is CO; R4 is alkyl, alkylenecarbocyclyl, or alkyleneheterocyclyl; R5 is (un)substituted alkyl; R5' is H; or CR5R5' is cycloalkyl; E is CO, SO0-2, NRaSO0-2, NRaCO, O2C, etc; Ra = H, alkyl, Ac; R6 is a stable, optionally substituted, mono- or bicyclic carbocycle or heterocycle] or their pharmaceutically-acceptable salts are claimed. Synthetic examples describe building blocks, e.g., 4-benzyl-6-fluorooctahydropyrrolo[3,2-b]pyrrol-3-ol, for the synthesis of compds. I.Except for chemicals metioned above, 771-99-3 and 860344-84-9 are also used. .