US 12,280,041 B2
Compounds and compositions for inducing chondrogenesis
Ha-Soon Choi, San Diego, CA (US); James Paul Lajiness, San Diego, CA (US); Srinivasa Reddy Natala, San Diego, CA (US); Bao Nguyen, San Diego, CA (US); Hank Michael James Petrassi, Fallbrook, CA (US); and Zhicheng Wang, San Diego, CA (US)
Assigned to NOVARTIS AG, Basel (CH)
Filed by NOVARTIS AG, Basel (CH)
Filed on Oct. 19, 2022, as Appl. No. 18/048,016.
Application 18/048,016 is a division of application No. 16/848,568, filed on Apr. 14, 2020, granted, now 11,510,912.
Application 16/203,122 is a division of application No. 15/587,652, filed on May 5, 2017, granted, now 10,188,638, issued on Jan. 29, 2019.
Application 15/587,652 is a division of application No. 14/709,852, filed on May 12, 2015, granted, now 9,688,689, issued on Jun. 27, 2017.
Application 16/848,568 is a continuation of application No. 16/448,547, filed on Jun. 21, 2019, granted, now 10,660,881, issued on May 26, 2020.
Application 16/448,547 is a continuation of application No. 16/203,122, filed on Nov. 28, 2018, granted, now 10,383,863, issued on Aug. 20, 2019.
Claims priority of provisional application 61/992,815, filed on May 13, 2014.
Prior Publication US 2023/0112980 A1, Apr. 13, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/443 (2006.01); A61K 31/34 (2006.01); A61K 31/351 (2006.01); A61K 31/4155 (2006.01); A61K 31/416 (2006.01); A61K 31/4245 (2006.01); A61K 31/4433 (2006.01); A61K 31/4439 (2006.01); A61K 31/444 (2006.01); A61K 31/4525 (2006.01); A61K 31/4545 (2006.01); A61K 31/497 (2006.01); A61K 31/506 (2006.01); A61K 31/5377 (2006.01); A61K 45/06 (2006.01); A61L 27/54 (2006.01); C07D 491/18 (2006.01); C07D 493/08 (2006.01); C12N 5/077 (2010.01)
CPC A61K 31/443 (2013.01) [A61K 31/34 (2013.01); A61K 31/351 (2013.01); A61K 31/4155 (2013.01); A61K 31/416 (2013.01); A61K 31/4245 (2013.01); A61K 31/4433 (2013.01); A61K 31/4439 (2013.01); A61K 31/444 (2013.01); A61K 31/4525 (2013.01); A61K 31/4545 (2013.01); A61K 31/497 (2013.01); A61K 31/506 (2013.01); A61K 31/5377 (2013.01); A61K 45/06 (2013.01); A61L 27/54 (2013.01); C07D 491/18 (2013.01); C07D 493/08 (2013.01); C12N 5/0655 (2013.01); A61L 2300/412 (2013.01); A61L 2430/06 (2013.01); C12N 2501/999 (2013.01); C12N 2506/1346 (2013.01)] 20 Claims
 
1. A method for treating cartilage damage, comprising administering to a subject in need thereof, a therapeutically effective amount of a pharmaceutical combination comprising a compound of Formula 1B and one or more therapeutic second agent;

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, or a stereoisomer thereof, wherein
R1 is phenyl or 5- or 6-membered heteroaryl, wherein
the phenyl or heteroaryl of R1 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, cyano, C1-6alkyl, C1-4haloalkyl, —C(O)R13, —C(O)OR—, —NR14aR14b, 5- and 6-membered heterocycloalkyl, phenyl, and 5- and 6-membered heteroaryl, wherein
R13 is C1-6alkyl or amino;
R14a and R14b are independently is selected from hydrogen, C1-6alkyl, —C(O)R15, and —C(O)OR15, wherein R15 is C1-4alkyl; and
the heterocycloalkyl, phenyl, or heteroaryl substituent of R1 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, hydroxy, and C1-6alkyl; and
R3 is phenyl or 5- or 6-membered heteroaryl, wherein the phenyl or heteroaryl is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, cyano, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, —C(O)R16, —C(O)OR16, 5- and 6-membered heterocycloalkyl, and phenyl, wherein
R16 is C1-6alkyl; and
the heterocycloalkyl or phenyl is unsubstituted or substituted by 1 to 2 substituents selected from halo and cyano.