US 11,931,350 B2
Opioid receptor ligands and methods of using and making same
Dennis Yamashita, Cambridge, MA (US); Dimitar Gotchev, Hatboro, PA (US); Philip Pitis, North Wales, PA (US); Xiao-Tao Chen, Furlong, PA (US); Guodong Liu, Jamison, PA (US); and Catherine C. K. Yuan, King of Prussia, PA (US)
Assigned to TREVENA, INC., Chesterbrook, PA (US)
Filed by TREVENA, INC., Chesterbrook, PA (US)
Filed on Jul. 2, 2021, as Appl. No. 17/367,021.
Application 17/367,021 is a continuation of application No. 15/828,695, filed on Dec. 1, 2017, granted, now 11,077,098.
Application 15/828,695 is a continuation of application No. 15/472,345, filed on Mar. 29, 2017, granted, now 9,849,119, issued on Dec. 26, 2017.
Application 15/472,345 is a continuation of application No. 15/093,315, filed on Apr. 7, 2016, granted, now 9,642,842, issued on May 9, 2017.
Application 15/093,315 is a continuation of application No. 14/712,974, filed on May 15, 2015, granted, now 9,309,234, issued on Apr. 12, 2016.
Application 14/712,974 is a continuation of application No. 13/964,505, filed on Aug. 12, 2013, granted, now 9,044,469, issued on Jun. 2, 2015.
Application 13/964,505 is a continuation of application No. 13/428,849, filed on Mar. 23, 2012, granted, now 8,835,488, issued on Sep. 16, 2014.
Claims priority of provisional application 61/596,808, filed on Feb. 9, 2012.
Claims priority of provisional application 61/466,809, filed on Mar. 23, 2011.
Prior Publication US 2022/0175747 A1, Jun. 9, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/4436 (2006.01); A61K 9/00 (2006.01); A61K 31/35 (2006.01); A61K 31/4433 (2006.01); A61K 31/444 (2006.01); A61K 45/06 (2006.01); C07D 311/96 (2006.01); C07D 405/04 (2006.01); C07D 405/12 (2006.01); C07D 405/14 (2006.01); C07D 409/12 (2006.01); C07D 409/14 (2006.01)
CPC A61K 31/4436 (2013.01) [A61K 9/0019 (2013.01); A61K 31/35 (2013.01); A61K 31/4433 (2013.01); A61K 31/444 (2013.01); A61K 45/06 (2013.01); C07D 311/96 (2013.01); C07D 405/04 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01); C07D 409/12 (2013.01); C07D 409/14 (2013.01)] 20 Claims
 
1. A compound, or a pharmaceutically acceptable salt thereof, having a formula of:

OG Complex Work Unit Chemistry
or a stereoisomer thereof,
wherein:
A2 is selected from the group consisting of CH2, CHR5, and CR5R6;
A4 is elected from the group consisting of CH2, CHR9, CR9R10, and a cycle of the formula C(CH2)n, where n=2-5, and when A4 is CH2, CR5R6 is not C(CH3)2, C(CH3)CH2CH3, or CHCH2(CH3)2 and when A2 is CH2, CR9R10 is not C(CH3)2, C(CH3)CH2CH3, or CHCH2(CH3)2;
R5, R6, R9 and R10 are independently selected from the group consisting of CH3, CH2CH3, CH2F, CHF2, CF3, n-Pr, n-Bu, i-Bu, sec-Bu, i-Pr, t-Bu, and phenyl;
B3 is selected from the group consisting of H, alkyl, branched alkyl, optionally substituted aryl, optionally substituted arylalkyl, alkoxycarbonyl, and alkylsulfonyl;
B4 is selected from the group consisting of null, CH2, CHR19, CR19R20, and CO;
B5 is selected from the group consisting of alkyl, branched alkyl, optionally substituted carbocycle, carbocycle-substituted alkyl, optionally substituted aryl, and optionally substituted arylalkyl; and
D1 is an optionally substituted heteroaryl.