US 11,945,805 B2
Inhibitors of CXCR2
Xi Chen, East Palo Alto, CA (US); Dean R. Dragoli, Los Altos, CA (US); Junfa Fan, Palo Alto, CA (US); Jaroslaw Kalisiak, Mountain View, CA (US); Manmohan Reddy Leleti, Dublin, CA (US); Viengkham Malathong, Mountain View, CA (US); Jeffrey McMahon, San Francisco, CA (US); Hiroko Tanaka, Mountain View, CA (US); Ju Yang, Palo Alto, CA (US); Chao Yu, Sunnyvale, CA (US); Penglie Zhang, Foster City, CA (US); and Venkat Mali, Cupertino, CA (US)
Assigned to CHEMOCENTRYX, INC, Thousand Oaks, CA (US)
Filed by CHEMOCENTRYX, INC., San Carlos, CA (US)
Filed on Apr. 29, 2021, as Appl. No. 17/243,872.
Application 17/243,872 is a continuation of application No. 16/438,880, filed on Jun. 12, 2019, granted, now 11,040,960.
Application 16/438,880 is a continuation of application No. 15/722,785, filed on Oct. 2, 2017, granted, now 10,370,363, issued on Aug. 6, 2019.
Application 15/722,785 is a continuation of application No. 15/353,949, filed on Nov. 17, 2016, granted, now 9,809,581, issued on Nov. 7, 2017.
Claims priority of provisional application 62/257,529, filed on Nov. 19, 2015.
Prior Publication US 2022/0009911 A1, Jan. 13, 2022
Int. Cl. C07D 405/12 (2006.01); A61K 31/4035 (2006.01); A61K 31/422 (2006.01); A61K 31/4439 (2006.01); A61K 45/06 (2006.01); A61P 11/00 (2006.01); A61P 17/06 (2006.01); A61P 35/00 (2006.01); A61P 37/00 (2006.01); C07B 59/00 (2006.01); C07D 405/14 (2006.01); C07D 413/12 (2006.01)
CPC C07D 405/12 (2013.01) [A61K 31/4035 (2013.01); A61K 31/422 (2013.01); A61K 31/4439 (2013.01); A61K 45/06 (2013.01); A61P 11/00 (2018.01); A61P 17/06 (2018.01); A61P 35/00 (2018.01); A61P 37/00 (2018.01); C07B 59/002 (2013.01); C07D 405/14 (2013.01); C07D 413/12 (2013.01); C07B 2200/05 (2013.01)] 9 Claims
 
1. A method of assaying a compound for CXCR2 antagonistic activity, said method comprising
(a) contacting the compound with cells expressing CXCR2 and a radioactive CXCR2 ligand to form a reaction mixture;
(b) transferring the reaction mixture onto a GF/B glass filter pre-soaked in a polyethyleneimine solution;
(c) measuring the amount radioactivity remaining on the GF/B glass filter, wherein said method comprises performing steps (a)-(c) with a positive control sample having a formula represented by the structure

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
R1 is selected from the group consisting of Cl and CH3;
R3b is selected from the group consisting of H and D;
R4 is a member selected from the group consisting of H and C1-8 alkyl, wherein the C1-8 alkyl is optionally substituted with —CONRaRb, —OC(O)NRaRb, —NRaC(O)Rb, —NRaC(O)2Rc, —NRaRb, and —ORa, wherein each Ra and Rb is independently selected from hydrogen, C1-4 alkyl, C1-4 hydroxyalkyl and C1-4 haloalkyl, and RC is selected from C1-4 alkyl, C1-4 hydroxyalkyl and C1-4 haloalkyl;
R5a and R5b are each members independently selected from the group consisting of H, F, Cl and CH3;
R6a and R6b are each members independently selected from the group consisting of H, C1-4 alkyl, C1-4 hydroxyalkyl and C1-4 haloalkyl; or optionally R6a and R6b are taken together to form oxo (═O).