Patent SG-11201803757U-A (SG)
Title: N-[2-(1 -benzylpiperidin-4-yl)ethyl]-4-(pyrazin-2-yl)-piperazine-1 -carboxamide derivatives and related compounds as muscarinic receptor 4 (m4) antagonists for treating neurological diseases
Inventor: HARRIOTT NICOLE
IPC: C07D401/12
Filed: 2016-11-04
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property -' Organization International Bureau (43) International Publication Date .... ..sr ,„„..) 11 May 2017(11.05.2017) WIPO I PCT (10) WO International 111111111111311111111111111111111111111111111111111111111111111111111111111111111111111111 2017/079641 Publication Al Number (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, C07D 401/12 (2006.01) A61K 31/4545 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, CO7D 211/26 (2006.01) A61P 25/28 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, CO7D 211/40 (2006.01) A61P 25/16 (2006.01) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, A61K 31/445 (2006.01) A61P 25/18 (2006.01) KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (21) International Application Number: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, PCT/US2016/060659 SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (22) International Filing Date: TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, 4 November 2016 (04.11.2016) ZW. (25) Filing Language: English (8 4 ) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (30) Priority Data: TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, 62/252,179 6 November 2015 (06.11.2015) US TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, 62/275,708 6 January 2016 (06.01.2016) US 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, (71) Applicant: NEUROCRINE BIOSCIENCES, INC. SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, [US/US]; 12780 El Camino Real, San Diego, California GW, KM, ML, MR, NE, SN, TD, TG). 92130 (US). Declarations under Rule 4.17: (72) Inventors: HARRIOTT, Nicole; 11340 Squamish Road, as to applicant's entitlement to apply for and be granted a San Diego, California 92126 (US). PAGANO, Nicholas; patent (Rule 4.17 (ii)) 1512 La Playa Avenue, Apartment 312, San Diego, Cali- fornia 92109 (US). — as to the applicant's entitlement to claim the priority of the earlier application (Rule 4.17(iii)) (74) Agents: HERMANNS, Karl, R. et al.; Seed Intellectual Property Law Group LLP, Suite 5400, 701 Fifth Avenue, Published: Seattle, Washington 98104-7064 (US). — with international search report (Art 21(3)) (81) Designated States (unless otherwise indicated, for every _ 19(1)) with amended claims (Art kind AE, AG, AL, AM, of national protection available): Title: (54) N-[2-(1 -BENZYLPIPERIDIN-4-YL)ETHYL]-4-(PYRAZIN-2-YL)-PIPERAZINE-1 -CARBOXAMIDE DERIVATIVES AND RE- LATED COMPOUNDS AS MUSCARINIC RECEPTOR 4 (M4) ANTAGONISTS FOR TREATING NEUROLOGICAL DISEASES (R2)w (R3)x Il .4t A 11 i t 0 \ IN (57) : Provided herein are small molecule 0 ---- ter or pharmaceutically acceptable salt thereof, Methods for treating diseases/ disorders by antagonizing 1:::j ceptor 4 (M4), are also disclosed. Such diseases/disorders el Lewy Body Dementia and the cognitive deficits ea ) dyskinesias, dystonia, chorea, levodopa induced Preferred compounds are e.g. 1\112-(1-benzylpiperidin-4-yflethyl]-4- compounds wherein the pyrazine has been replaced N '- ''' .--r 'Th-] wherein dyskinesia, by compounds associated ) o,i A, B, are muscarinic cerebral e.g. pyridazine, (IR,Oy B L2 of the following C, L I , L 2, e.g. neurological with schizophrenia, palsy, receptors, pyrimidine, r-7\ C .Y R I , R R R R 2, progressive (pyrazin-2-y1)-piperazine-1-carboxamide formula diseases/disorders sh (I) (I): or a stereoisomer, tautomer, solvate, es - 3, 4, 5, w, x, y and z are as defined herein. including specifically antagonizing muscarinic re - such as e.g. Alzheimer's Disease, Parkinson's Disease, drug induced Parkinsonism, supranuclear palsy, and Huntington's disease. derivatives and related pyridine or phenyl.