Patent SG-11201806307Y-A (SG)
Title: Pyrazolo[1,5-a]pyrazin-4-yl derivatives as jak-inhibitors
Inventor: BROWN MATTHEW FRANK
IPC: C07D487/04
Filed: 2017-02-10
Abstract: WO 17 / 144995 Al (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/144995 Al 31 August 2017 (31.08.2017) WIPO I PCT (51) International Patent Classification: CO7D 487/04 (2006.01) A61P 29/00 (2006.01) A61K 31/4985 (2006.01) A61P 25/28 (2006.01) A61P 37/02 (2006.01) (21) International Application Number: PCT/IB2017/050748 (22) International Filing Date: 10 February 2017 (10.02.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/299,130 24 February 2016 (24.02.2016) US (71) Applicant: PFIZER INC. [US/US]; 235 East 42nd Street, New York, New York 10017 (US). (72) Inventors: BROWN, Matthew Frank; 443 Wheeler Road, Stonington, Connecticut 06378 (US). DERMENCI, Alpay; 9 Peach Lane, East Lyme, Connecticut 06333 (US). FENSOME, Andrew; 260 Bolton Road, Harvard, Mas- sachusetts 01451 (US). GERSTENBERGER, Brian Stephen; 210 Winthrop Road, #9, Brookline, Massachu- setts 02445 (US). HAYWARD, Matthew Merrill; 3 Pyr- us Court, Old Lyme, Connecticut 06371 (US). OWEN, Dafydd Rhys; 98 Peter Bulkeley Road, Concord, Mas- sachusetts 01742 (US). WRIGHT, Stephen Wayne; 1 Whitman Lane, Old Lyme, Connecticut 06371 (US). XING, Li Huang; 8 Great Rock Road, Lexington, Mas- sachusetts 02421 (US). YANG, Xiaojing; 18 Maple Ter- race, Waterford, Connecticut 06385 (US). (74) Agent: WALDRON, Roy, F.; Pfizer Inc., 235 East 42nd Street, MS 235/9/S20, New York, NY 10017 (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, 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, [Continued on next page] (54) Title: PYRAZOLO[1,5-A]PYRAZIN-4-YL DERIVATIVES AS JAK-INHIBITORS NC N—N R1 Ra (57) : A compound compound having the structure (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein A, A' and A\" are independently 0, C=O, C-R' or N-R\", where R' and R\" may independently be H, amino, -NR 7 COR, COR, -CONR 6 E 7 R s , C 1 -C 6 alkyl, or hydroxy(C i -C alkyl), and R\" 6 may be present or absent, and is present where the rules of valency permit, and where not more than one of A, A' and A\" is 0 or C=0; R and R are independently H, Br, CI, F, or C alkyl; R o 1 -C 6 1 is H, C 1 -C alkyl, or hydroxy(C 6 i -C 6 alkyl); R2 is selected from the group consisting of H, C,-C6 alkyl, C,-C6 alkoxy, hydroxy(Ci-C6 alkyl), phenyl(Ci-C6 alkyl), formyl, heteroaryl, heterocyclic, -COR E , -OCOR, -COOR 6 6 , -NR 7 COR 6 , -CONR 7 R s , and -(CH 2 )„-W, where W is cyano, hydroxy, C -C s s cycloalkyl, -SONR 2 7 R s , and -502-R9, where R9 is C,-C6 alkyl, Cs-Cs cycloalkyl, heteroaryl, or heterocyclic; wherein each of said alkyl, cycloalkyl, heterocyclic, or heteroaryl may be unsubstituted or substituted by halo, cyano, hydroxy, or C I -C 6 alkyl; X is C-R 3 or N, where may be H or C R3 1 - C6 alkyl; R4 and Rs are independently H, amino, Ci-C6 alkyl, or hydroxy(Ci-C6 alkyl); R6, R7 and Rs are each independently H, Ci-C6 alkyl, C I -C I alkoxy(C i -C 6 alkyl), or C s -C s cycloalkyl, said C 1 - C6 alkyl is optionally substituted by halo, CN or hydroxy; or, R7 and R together with the atom bonded thereto form a 5- or 6-membered ring, said ring being 8 [Continued on next page] 1111111111111101110111111111110101111101110101111111111110111111111111111111110111111 WO 2017/144995 All#11101M01101010IIM010130101101111011111 IIO1110V0IS 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 the identity of the inventor (Rule 4.17(0) as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(ii)) 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)) optionally substituted by halo, hydroxy, CN, or Ci-C6 alkyl; and, n is 0, 1, 2 or 3. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations thereof with oth- er therapeutic agents.