SG11201908615RA - 6-6 fused bicyclic heteroaryl compounds and their use as lats inhibitors - Google Patents

6-6 fused bicyclic heteroaryl compounds and their use as lats inhibitors

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Publication number
SG11201908615RA
SG11201908615RA SG11201908615RA SG11201908615RA SG 11201908615R A SG11201908615R A SG 11201908615RA SG 11201908615R A SG11201908615R A SG 11201908615RA SG 11201908615R A SG11201908615R A SG 11201908615RA
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Singapore
Prior art keywords
novartis
san diego
institute
california
functional genomics
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Inventor
Dirk Behnke
Frada Berenshteyn
Xueshi Hao
Timothy Hoffman
Qihui Jin
Arnaud Lacoste
Cameron Lee
Jun Liu
Yahu Liu
Juergen Klaus Maibaum
Tingting Mo
Jianfeng Pan
Xin Qu
Jan Tchorz
Yun Feng Xie
Shanshan Yan
Yefen Zou
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Novartis Ag
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Publication of SG11201908615RA publication Critical patent/SG11201908615RA/en

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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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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)
SG11201908615R 2017-04-28 2018-04-26 6-6 fused bicyclic heteroaryl compounds and their use as lats inhibitors SG11201908615RA (en)

Applications Claiming Priority (6)

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US201762491526P 2017-04-28 2017-04-28
US201762491573P 2017-04-28 2017-04-28
US201762491475P 2017-04-28 2017-04-28
US201762491484P 2017-04-28 2017-04-28
US201862650232P 2018-03-29 2018-03-29
PCT/IB2018/052919 WO2018198077A2 (en) 2017-04-28 2018-04-26 6-6 fused bicyclic heteroaryl compounds and their use as lats inhibitors

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SG11201907434RA (en) 2017-03-22 2019-10-30 Novartis Ag Compositions and methods for immunooncology
JOP20190257A1 (en) 2017-04-28 2019-10-28 Novartis Ag 6-6 fused bicyclic heteroaryl compounds and their use as lats inhibitors
WO2019235569A1 (en) 2018-06-08 2019-12-12 日産化学株式会社 Kinase inhibitor
PE20211805A1 (en) 2018-06-29 2021-09-14 Incyte Corp FORMULATIONS OF AN AXL / MER INHIBITOR
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