Patent SG-11201806416X-A (SG)
Title: Tetrahydroisoquinoline derivatives
Inventor: SATO IPPEI
IPC: C07D217/08
Filed: 2017-02-10
Abstract: 3000 g 2000 .S 0 2 1000 0 N=9/group mean ± SEM *p<0.05, vs. vehicle paired t-test Vehicle 1 mg/kg 3 mg/kg Exam ple 20 3000- 5 2000- +, Vehicle 3 mg/kg Example 22b W O 20 17 / 1395 26 Al 0 1000- 0 N=16/group mean ± SEM *p<0.05, paired t-test (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/139526 Al 17 August 2017 (17.08.2017) WIPO I PCT 11111111111111011101111111111101011111011101110111111111111111111111111111111110111111 (51) International Patent Classification: A61K 31/47 (2006.01) CO7D 217/08 (2006.01) (21) International Application Number: PCT/US2017/017295 (22) International Filing Date: 10 February 2017 (10.02.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/285,039 12 February 2016 (12.02.2016) US (71) Applicants: ASTELLAS PHARMA INC. [US/US]; 5-1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103-8411 (US). CYTOKINETICS, INCORPORATED [US/US]; 280 East Grand Avenue, South San Francisco, CA 94080 (US). (72) Inventors: SATO, Ippei; C/o Astellas Pharma Inc., 5-1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103-8411 (JP). KAMIKUBO, Takashi; C/o Astellas Pharma Inc., 5- 1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103- 8411 (JP). MIURA, Masanori; C/o Astellas Pharma Inc., 5-1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103- 8411 (JP). MATSUSHIMA, Yuji; C/o Astellas Pharma Inc., 5-1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103-8411 (JP). TANAKA, Hiroaki; C/o Astellas Pharma Inc., 5-1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103-8411 (JP). SHIINA, Yasuhiro; C/o Astellas Pharma Inc., 5-1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103-8411 (JP). YAMAKI, Susumu; C/o Astellas Pharma Inc., 5-1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103-8411 (JP). SAITO, Tomoyuki; C/o Astellas Pharma Inc., 5-1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103-8411 (JP). KIYOHARA, Hiroshi; C/o Astellas Pharma Inc., 5-1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103-8411 (JP). OHE, Munemichi; C/o Astellas Pharma Inc., 5-1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103-8411 (JP). MIHARA, Kayoko; C/o Astellas Pharma Inc., 5-1, Nihonbashi-honcho 2-chome, Chuo-ku, Tokyo, 103-8411 (JP). MORGAN, Bradley, Paul; 1206 Rimer Drive, Moraga, CA 94556 (US). MALIK, Fady; 2884 Hillside Drive, Burlingame, CA 94010 (US). COL- LIBEE, Scott, Emile; 2065 Brittan Avenue, San Carlos, CA 94070 (US). ASHCRAFT, Luke; 668 Caroline Street, San Francisco, CA 94107 (US). LU, Pu-Ping; 1017 Flying Fish Street, Foster City, CA 94404 (US). WARRING- TON, Jeffrey, Michael; 1936 Playa Street, San Mateo, [Continued on next page] (54) Title: TETRAHYDROISOQUINOLINE DERIVATIVES FIG. 1 (57) : Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sar- comere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) dis- orders of voluntary muscle, 3) CNS disorders in which muscle weak- ness, atrophy, and fatigue are prominent symptoms, 4) muscle symp- toms stemming from systemic disorders, and 5) dysfunctions of pel- vic floor and urethral/anal sphincter muscle. 4000- WO 2017/139526 Al MIDEDIMOMOIDIONOIDEMOMMIHIHIMIROMEHOIS CA 94403 (US). GARARD, Marc; 16745 Kildare Road, San Leandro, CA 94578 (US). (74) Agents: BAXTER, Stephen, G. et al.; Oblon, McClel- land, Maier & Neustadt, L.L.P., 1940 Duke Street, Alex- andria, VA 22314 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: with international search report (Art. 2 1 (3)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h))