Patent SG-11201908615R-A (SG)
Title: 6-6 fused bicyclic heteroaryl compounds and their use as lats inhibitors
Inventor: BEHNKE DIRK
IPC: A61P17/02
Filed: 2018-04-26
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 01 November 2018 (01.11.2018) WIPO I PCT omit VIII °nolo VIII 110 mmoiliollIE (10) International Publication Number WO 2018/198077 A3 (51) International Patent Classification: CO7D 487/04 (2006.01) Cl 2N 5/079 (2010.01) CO7D 519/00 (2006.01) A61P 17/02 (2006.01) A61K 35/30 (2015.01) (21) International Application Number: PCT/IB2018/052919 (22) International Filing Date: 26 April 2018 (26.04.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/491,475 28 April 2017 (28.04.2017) US 62/491,484 28 April 2017 (28.04.2017) US 62/491,526 28 April 2017 (28.04.2017) US 62/491,573 28 April 2017 (28.04.2017) US 62/650,232 29 March 2018 (29.03.2018) US (71) Applicant: NOVARTIS AG [CH/CH]; Lichtstrasse 35, 4056 Basel (CH). (72) Inventors: BEHNKE, Dirk; Novartis Pharma AG, Post- fach, 4002 Basel (CH). BERENSHTEYN, Frada; Novar- tis Institutes for BioMedical Research, Inc., 250 Massa- chusetts Avenue, Cambridge, Massachusetts 02139 (US). HAO, Xueshi; Novartis Institute for Functional Genomics, Inc., 10675 John Jay Hopkins Drive, San Diego, Califor- nia 92121 (US). HOFFMAN, Timothy; Novartis Institute for Functional Genomics, Inc., 10675 John Jay Hopkins Drive, San Diego, California 92121 (US). JIN, Qihui; No- vartis Institute for Functional Genomics, Inc., 10675 John Jay Hopkins Drive, San Diego, California 92121 (US). LA- COSTE, Arnaud; Novartis Institutes for BioMedical Re- search, Inc., 250 Massachusetts Avenue, Cambridge, Mass- achusetts 02139 (US). LEE, Cameron; Novartis Institutes for BioMedical Research, Inc., 250 Massachusetts Avenue, Cambridge, Massachusetts 02139 (US). LIU, Jun; Novar- tis Institute for Functional Genomics, Inc., 10675 John — (54) Title: 6-6 FUSED BICYCLIC HETEROARYL COMPOUNDS AND THEIR USE AS LATS INHIBITORS A2 Al Fig. 1 OMSO Ex. 49 Ex, 133 75K0 75K0 42KD phospho-YAP (Serl 27) Total YAP f3-actin W O 20 18/ 198077 A3 (57) : The present invention is related to 6-6 Fused Bicyclic Heteroaryl Compounds of the Formula A2 or Al and their Use as LATS Inhibitors, or a salt, stereoisomer or pharmaceutical composition thereof; wherein the variables are as defined herein (Al & A2). The present invention further relates to a method of LATS inhibition in a cell population using a compound of Formula Al, or a salt, stereoisomer or pharmaceutical composition thereof. The present invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, their use in the treatment and management of diseases or disorders. [Continued on next page] WO 2018/198077 A3 MUNRO DOI 010 VIII VIII IIIII 30HHEIBEREON Jay Hopkins Drive, San Diego, California 92121 (US). LIU, Yahu; Novartis Institute for Functional Genomics, Inc., 10675 John Jay Hopkins Drive, San Diego, California 92121 (US). MAIBAUM, Juergen Klaus; Novartis Phar- ma AG, Postfach, 4002 Basel (CH). MO, Tingting; Novar- tis Institute for Functional Genomics, Inc., 10675 John Jay Hopkins Drive, San Diego, California 92121 (US). PAN, Jianfeng; Novartis Institute for Functional Genomics, Inc., 10675 John Jay Hopkins Drive, San Diego, California 92121 (US). QU, Xin; Novartis Institutes for Biomed- ical Research, Inc., 250 Massachusetts Avenue, Cambridge, Massachusetts 02139 (US). TCHORZ, Jan; Novartis Phar- ma AG, Postfach, 4002 Basel (CH). XIE, Yun Feng; No- vartis Institute for Functional Genomics, Inc., 10675 John Jay Hopkins Drive, San Diego, California 92121 (US). YAN, Shanshan; Novartis Institute for Functional Ge- nomics, Inc., 10675 John Jay Hopkins Drive, San Diego, California 92121 (US). ZOU, Yefen; Novartis Institute for Functional Genomics, Inc., 10675 John Jay Hopkins Drive, San Diego, California 92121 (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). Declarations under Rule 4.17: as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(0) as to the applicant's entitlement to claim the priority of the earlier application (Rule 4.17(iii)) Published: with international search report (Art. 21(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)) with sequence listing part of description (Rule 5.2(a)) in black and white; the international application as filed contained color or greyscale and is available for download from PATENTSCOPE (88) Date of publication of the international search report: 14 February 2019 (14.02.2019)