Patent SG-11201805272X-A (SG)
Title: 4-amino-2-(1h-pyrazolo[3,4-b]pyridin-3-yl)-6-oxo-6,7-dihydro-5h-pyrrolo[2,3-d]pyrimidine derivatives and the respective (1h-indazol-3-yl) derivatives as cgmp modulators for treating cardiovascular diseases
Inventor: BERGER RAPHELLE
IPC: A61P9/04
Filed: 2016-12-20
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 29 June 2017 (29.06.2017) WIPOIPCT (10) International Publication Number WO 2017/112617 A1 (51) International Patent Classification: C07D 487/04 (2006.01) A61P 9/10 (2006.01) A61K31/519 (2006.01) A61P 9/12 (2006.01) A61P 9/00 (2006.01) A61P 9/04 (2006.01) (21) International Application Number: (22) International Filing Date: (25) Filing Language: (26) Publication Language: PCT/US2016/067654 20 December 2016 (20.12.2016) English (30) Priority Data: PCT/CN2015/098251 22 December 2015 (22.12.2015) English CN (71) Applicant (for all designated States except US): MERCK SHARP & DOHME CORP. [US/US]; 126 East Lincoln Avenue, Rahway, New Jersey 07065-0907 (US). (72) Inventors; and (71) Applicants (for NZ, US only)-. BERGER, Raphelle [FR/US]; 126 East Lincoln Avenue, Rahway, New Jersey 07065-0907 (US). CHEN, Yi-Heng [US/US]; 126 East Lincoln Avenue, Rahway, New Jersey 07065-0907 (US). LI, Guoqing [US/US]; 2000 Galloping Hill Road, Kenil- worth, New Jersey 07033 (US). GARFUNKLE, Joie [US/US]; 600 Coporate Drive, Lebanon, New Jersey 08833 (US). LI, Hong [CN/US]; 126 East Lincoln Aven­ ue, Rahway, New Jersey 07065-0907 (US). MIAO, Shouwu [CN/US]; 295 Prestwick Way, Edison, New Jer­ sey 08820 (US). RAGHAVAN, Subharekha [US/US]; 2000 Galloping Hill Road, Kenilworth, New Jersey 07033 (US). SMITH, Cameron, J. [US/US]; 9004 Snowford Court, Montgomery Village, Maryland 20886-4017 (US). STELMACH, John [US/US]; 228 Seneca Place, West- field, New Jersey 07090 (US). WHITEHEAD, Alan [US/US]; 126 East Lincoln Avenue, Rahway, New Jersey 07065-0907 (US). ZHANG, Rui [US/US]; 2000 Galloping Hill Road, Kenilworth, New Jersey 07033 (US). ZHANG, Yong [US/US]; 126 East Lincoln Avenue, Rahway, New Jersey 07065-0907 (US). FU, Jianmin [US/CN]; 6 Tai-He Road, BDA, Beijing 100176 (CN). JI, Gang [CN/CN]; 6 Tai-He Road, BDA, Beijing 100176 (CN). JIANG, Falong [CN/CN]; 6 Tai-He Road, BDA, beijing 100176 (CN). (74) Common Representative: MERCK SHARP & DOHME CORP.; 126 East Lincoln Avenue, Rahway, New Jersey 07065-0907 (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, [Continued on next page] (54) Title: 4-AMINO-2-(lH-PYRAZOLO[3,4-B]PYRIDIN-3-YL)-6-OXO-6,7-DIHYDRO-5H-PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES AND THE RESPECTIVE (1H-INDAZOL-3-YL) DERIVATIVES AS CGMP MODULATORS FOR TREATING CARDIOVASCULAR DISEASES l> CJ o CJ o & (R (I) (57) : The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1, R2, R4, Ra, and the sub­ scripts m, p, and q are as described herein. The com­ pounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate ("cGMP"), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance, such as cardiovascular disease, endothelial dysfunction, dia­ stolic dysfunction, atherosclerosis, hypertension, heart failure, pulmonary hypertension (WHO groups I, II, III, IV), angina pectoris, thrombosis, restenosis, myocardial infarction, stroke, cardiac insufficiency, fibrosis, pulmonary hypertonia, erectile dysfunction, asthma, acute respiratory distress syndrome (ARDS), chronic kidney disease, cystic fibrosis, sickle cell an­ emia, scleroderma, Raynaud's Syndrome, diabetes, diabetic retinopathy, cirrhosis of the liver, chronic ob­ structive pulmonary disease (COPD), acute lung in­ jury, pulmonary fibrosis or interstitial lung disease. The invention also provides pharmaceutical composi­ tions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The inven­ tion also relates to the compounds or their pharma­ ceutically acceptable salts for use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose. wo 2017/112617 AI i inn nil ii mil mi mil in mi i ii 111 mi mi mi mi mi mi mini mi 111 mi HN, HR, HU, ID, IL, IN, IR, IS, 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(H)) — 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))