US 11,952,386 B2
N-azaspirocycloalkane substituted N-heteroaryl compounds and compositions for inhibiting the activity of SHP2
Christine Hiu-Tung Chen, Waltham, MA (US); Zhuoliang Chen, Belmont, MA (US); Michael Dore, Saint-Bruno-de-Montarville (CA); Jorge Garcia Fortanet, Wilmington, MA (US); John William Giraldes, Windsor Mill, MD (US); Rajesh Karki, Quincy, MA (US); Mitsunori Kato, Long Island, NY (US); Matthew J. LaMarche, Reading, MA (US); Lawrence Blas Perez, Silver Spring, MD (US); Martin Sendzik, Belmont, MA (US); Troy Douglas Smith, Nashua, NH (US); Bakary-Barry Toure, Weston, MA (US); and Sarah Williams, Livermore, CA (US)
Assigned to NOVARTIS AG, Basel (CH)
Filed by NOVARTIS AG, Basel (CH)
Filed on Feb. 23, 2021, as Appl. No. 17/182,756.
Application 17/182,756 is a division of application No. 16/418,978, filed on May 21, 2019, granted, now 10,968,235.
Application 16/418,978 is a division of application No. 15/899,821, filed on Feb. 20, 2018, granted, now 10,336,774, issued on Jul. 2, 2019.
Application 15/899,821 is a division of application No. 15/110,511, granted, now 10,077,276, issued on Sep. 18, 2018, previously published as PCT/IB2015/050345, filed on Jan. 16, 2015.
Claims priority of provisional application 61/991,129, filed on May 9, 2014.
Claims priority of provisional application 61/928,754, filed on Jan. 17, 2014.
Prior Publication US 2022/0396585 A1, Dec. 15, 2022
Int. Cl. C07D 241/18 (2006.01); C07D 241/20 (2006.01); C07D 401/04 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/04 (2006.01); C07D 471/10 (2006.01); C07D 491/107 (2006.01); C07D 495/10 (2006.01); C07D 498/10 (2006.01)
CPC C07D 498/10 (2013.01) [C07D 241/18 (2013.01); C07D 241/20 (2013.01); C07D 401/04 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/04 (2013.01); C07D 471/10 (2013.01); C07D 491/107 (2013.01); C07D 495/10 (2013.01); C07B 2200/07 (2013.01)] 12 Claims
 
1. A compound of formula:

OG Complex Work Unit Chemistry
wherein:
Y1 is N;
Y2 is CR6;
R1 is —XR1a; wherein
R1a is selected from C6-10aryl, C3-8cycloalkyl, C3-8cycloalkenyl and a 5-9 member heteroaryl group containing from 1 to 4 heteroatoms or groups independently selected from N, C(O), O and S; wherein said aryl or heteroaryl of R1a is substituted with 1 to 5 R9 groups independently selected from halo, amino, hydroxy, N3, C1-4alkoxy, C1-4alkyl, dimethyl-amino, hydroxy-substituted—C1-4alkyl, halo-substituted-C1-4alkyl, amino-substituted-C1-4alkyl, —C(O)OR10, —C(O)NH2, and —NHC(O)R10; wherein R10 is selected from hydrogen, phenyl, and naphthyl; wherein said phenyl of R10 is unsubstituted or substituted with methoxy;
X is selected from S(O)m, O, CR10aR10b, NR11; wherein m is selected from 0, 1 and 2; each R10a and R10b is independently selected from halo and C1-4alkyl; and R11 is selected from hydrogen and C1-4alkyl; and
R6 is selected from hydrogen, halo, cyano, C1-4alkyl, C1-4alkoxy, amino-carbonyl, halo-substituted C1-4alkyl, halo-substituted C1-4alkoxy, hydroxy-substituted C1-4alkyl, amino-substituted C1-4alkyl, —S(O)1-2R6a, —C(S)R6a, —C(O)NR6aR6b, —C(NH)NR6aR6b and —NR6aC(O)R6b; wherein R6a and R6b are independently selected from hydrogen and C1-4alkyl; or a pharmaceutically acceptable salt thereof.