ANTIPROLIFERATIVE COMPOUNDS AND METHODS OF USE THEREOF

• Main Authors: KERCHER, Timothy, NAGY, Mark, TAVARES-GRECO, Paula, HAVENS, Courtney, LOPEZ-GIRONA, Antonia, PICCOTTI, Joseph, CARMICHAEL, James, NARLA, Rama, LU, Xiaoling, WHITEFIELD, Brandon, HANSEN, Joshua, WONG, Lilly, CORREA, Matthew, CATHERS, Brian E, BRAY, Gordon, CARRANCIO, Soraya, ALEXANDER, Matthew, MAN, Hon-Wah, PIERCE, Daniel, ARTMAN, Gerald, ZOU, Nanfei
• Format: Patent
• Language: English
• Published: 27.02.2020
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

INTERNATIONAL APPLICATION (19) World Intellectual Property Organization International Bureau PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) vitivio VIII oviolo ~~~ I D oimIE (43) International Publication Date 17 January 2019 (17.01.2019) (10) International Publication Number WO 2019/014100 Al WIPO I PCT Cmpd No. Total AUC Compd A 1232 Compd 1 1547.5 Figure 1B MICHAEL, James [GB/GB]; 11 Cherry Tree Lane, Ed- walton, Nottingham NG12 4AL (GB). CARRANCIO, So- raya [ES/US]; 5205 Fiore Terrace, Apt. B419, San Diego, CA 92122 (US). CATHERS, Brian E. [US/US]; 10040 Branford Road, San Diego, CA 92129 (US). CORREA, Matthew, D. [US/US]; 9025 Three Seasons Road, San Diego, CA 92126 (US). HANSEN, Joshua [US/US]; 5633 Bellevue Avenue, La Jolla, CA 92037 (US). HAVENS, Courtney, G. [US/US]; 3504 Felton Street, San Diego, CA 92104 (US). KERCHER, Timothy, S. [US/US]; 11283 Paul Barwick Court, San Diego, CA 92126 (US). LOPEZ- GIRONA, Antonia [US/US]; 8959 January Place, San Diego, CA 92122 (US). LU, Xiaoling [CN/US]; 3 Run- nymede Court, Whippany, NJ 07981 (US). MAN, Hon- Wah [US/US]; 27 Grant Way, Princeton, NJ 08540 (US). NAGY, Mark, A. [US/US]; 345 Willowspring Drive N., Encinitas, CA 92024 (US). NARLA, Rama, K. [US/US]; 5157 Great Meadow Drive, San Diego, CA 92130 (US). PICCOTTI, Joseph, R. [US/US]; 742 Rihely Place, Encinitas, CA 92024 (US). PIERCE, Daniel, W. [US/US]; 3406 Lodge Drive, Belmont, CA 94002 (US). TAVARES- GRECO, Paula, A. [BR/US]; 300 Parsippany Road, Par- sippany, NJ 07054 (US). WHITEFIELD, Brandon, W. [US/US]; 6406 Friars Road, #335, San Diego, CA 92108 (US). WONG, Lilly, L. [US/US]; 871 Viva Court, Solana (51) International Patent Classification: A61K 31/496 (2006.01) A61K 31/573 (2006.01) CO7D 241/02 (2006.01) A61P 35/00 (2006.01) A61K 38/05 (2006.01) (21) International Application Number: PCT/US2018/041230 (22) International Filing Date: 09 July 2018 (09.07.2018) English English (25) Filing Language: (26) Publication Language: (30) Priority Data: 62/530,778 10 July 2017 (10.07.2017) US 62/593,185 30 November 2017 (30.11.2017) US 62/675,581 23 May 2018 (23.05.2018) US (71) Applicant: CELGENE CORPORATION [US/US]; 86 Morris Avenue, Summit, NJ 07901 (US). (72) Inventors; and (71) Applicants: ALEXANDER, Matthew, D. [US/US]; 12488 Carmel Cape, San Diego, CA 92130 (US). ART- MAN, Gerald, D., III [US/US]; 8 Halls Mill Road, As- bury, NJ 08802 (US). BRAY, Gordon, L. [US/US]; 301 Main Street, Unit 8C, San Francisco, CA 94105 (US). CAR- (54) Title: ANTIPROLIFERATWE COMPOUNDS AND METHODS OF USE THEREOF (57) : Provided herein is 4-(4-(44(2-(2,6-dioxopiperidin-3-y1)-1-oxoisoin- -* Compound A dolin-4-yfloxy)methypbenzyppiperazin- 1 -y1)-3-fluorobenzonitrile, or an enantiomer, a 600 mixture of enantiomers, a tautomer, or a pharmaceutically acceptable salt thereof, and -v- Compound 1 methods for treating, preventing or managing multiple myeloma using such compounds. Also provided are pharmaceutical compositions comprising the compounds, and methods of use of the compositions. 1 2 log[cpd], nM Figure 1A A - I Compound A Compound 1 W O 20 19/0 14100 Al [Continued on next page] WO 2019/014100 Al MIDEDIMOMOIDEIROMOIONIMMEIEDIONHEMOM1011 Beach, CA 92075 (US). ZOU, Nanfei [US/US]; 66 Wood- land Avenue, Fanwood, New Jersey 07023 (US). (74) Agent: BRUNER, Michael, J. et al.; Jones Day, 250 Vesey Street, New York, NY 10281-1047 (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, JO, 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. 21(3))