Patent SG-11201810794V-A (SG)
Title: Positive allosteric modulators of the muscarinic acetylcholine receptor m4
Inventor: LINDSLEY CRAIG W
IPC: A61K31/5025
Filed: 2017-06-22
Abstract: International Patent Classification: A61K 31/395 (2006.01) C07D 495/04 (2006.01) A61K 31/5025 (2006.01) (21) International Application Number: PCT/US2017/038711 (22) International Filing Date: 22 June 2017 (22.06.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: (72) Inventors: LINDSLEY, Craig W.; 9281 Wardley Park Lane, Brentwood, TN 37027 (US). CONN, P. Jeffrey; 2806 Acklen Avenue, Nashville, TN 37212 (US). ENGERS, Darren W.; 1744 Stillwater Circle, Brentwood, TN 37027 (US). BOLLINGER, Sean; 140 Melstone Court, Murfrees- boro, TN 37127 (US). TARR, James C.; 324 Wisteria Dri- ve, Franklin, TN 37064 (US). SPEARING, Paul; 1820 Sawgrass Lane, Chapel Hill, TN 37034 (US). ENGERS, Julie L.; 1744 Stillwater Circle, Brentwood, TN 37027 (US). LONG, Madeline; 4110 Idaho Avenue, Nashville, TN 37209 (US). BRIDGES, Thomas M.; 205 31st Avenue North, #212, Nashville, TN 37203 (US). 62/353,447 22 June 2016 (22.06.2016) US (74) Agent: REYNOLDS, Anne M.; Michael Best & Friedrich 62/418,638 07 November 2016 (07.11.2016) US LLP, 100 East Wisconsin Avenue, Suite 3300, Milwaukee, 62/471,281 14 March 2017 (14.03.2017) US WI 53202-4108 (US). (71) Applicant: VANDERBILT UNIVERSITY [US/US]; 305 (81) Designated States (unless otherwise indicated, for every Kirkland Hall, 2201 West End Avenue, Nashville, TN 37240 (US). 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, (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 28 December 2017 (28.12.2017) WIPO I PCT = (54) Title: POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4 Allosteric binding site Orthosteric binding site FIGURE 1 cr (57) : Disclosed herein are tricyclic compounds, including pyrimido [4',5':4,5]thieno [2, 3- c]pyridazine-8-amine, pyrido [3',2M,5]thieno [3,2 -d]pyrimidine-4-amine, pyrazino [2',3':4,5]thieno [3,2-d]pyrimidin-4 -amine, pyrido[3',2':4,5]furo[3,2-d]pyrimidin-4- amine, and pyrimido[4',5':4,5]furo[2,3-c]pyridazin-8-amine compounds, which may be useful N making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating neurological and psychiatric as positive allosteric modulators of the muscarinic acetylcholine receptor M (mAChR M4). Also disclosed herein are methods of 4 O disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. [Continued on next page] o 1E1 Ho VIII Hot o Hum! oo1 om mo 110111110lII ow (10) International Publication Number WO 2017/223290 Al WO 2017/223290 Al IMEDIMOM0101011MMEMODIMOMMOHMOMMEHOIMIE 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)) 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))