US 11,840,541 B2
Opioid receptor modulators
Andrew C. Kruegel, New York, NY (US); Madalee G. Wulf, Beverly, MA (US); Jonathan A. Javitch, Dobbs Ferry, NY (US); and Dalibor Sames, New York, NY (US)
Assigned to THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, New York, NY (US)
Appl. No. 15/528,339
Filed by Andrew C. Kruegel, New York, NY (US); Madalee G. Wulf, Beverly, MA (US); Jonathan A. Javitch, Dobbs Ferry, NY (US); and Dalibor Sames, New York, NY (US)
PCT Filed Nov. 25, 2015, PCT No. PCT/US2015/062726
§ 371(c)(1), (2) Date May 19, 2017,
PCT Pub. No. WO2016/086158, PCT Pub. Date Jun. 2, 2016.
Claims priority of provisional application 62/084,994, filed on Nov. 26, 2014.
Claims priority of provisional application 62/204,318, filed on Aug. 12, 2015.
Prior Publication US 2017/0334923 A1, Nov. 23, 2017
Int. Cl. C07D 491/12 (2006.01); C07D 491/18 (2006.01); A61P 25/24 (2006.01); A61P 25/04 (2006.01); C07D 495/18 (2006.01); C07D 471/18 (2006.01); A61K 9/00 (2006.01); A61K 9/70 (2006.01); A61K 31/485 (2006.01); A61K 47/38 (2006.01)
CPC C07D 491/18 (2013.01) [A61K 9/0073 (2013.01); A61K 9/7092 (2013.01); A61K 31/485 (2013.01); A61P 25/04 (2018.01); A61P 25/24 (2018.01); C07D 471/18 (2013.01); C07D 495/18 (2013.01); A61K 9/0002 (2013.01); A61K 47/38 (2013.01)] 27 Claims
 
1. A compound having the structure:

OG Complex Work Unit Chemistry
wherein
Y1 is H, -(alkyl), -(alkenyl), -(alkynyl),—(C3-C5 cycloalkyl), -(haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(C3-C5cycloalkyl);
Y2 is H, -(alkyl), -(alkenyl), -(alkynyl), —(C3-C5cycloalkyl), -(haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(C3-C5cycloalkyl);
Y3 is H, -(alkyl), -(alkenyl), -(alkynyl), —(C3-C5cycloalkyl), -(haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(C3-C5cycloalkyl);
Y4 is H, -(alkyl), -(alkenyl), -(alkynyl), —(C3-C5cycloalkyl), -(haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(C3-C5cycloalkyl);
Y5 is H, -(alkyl), -(alkenyl), -(alkynyl), —(C3-C5cycloalkyl), -(haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(C3-C5cycloalkyl);
R1, R2, R3 and R4 are each independently —H, -(alkyl), -(alkenyl), -(alkynyl), -(haloalkyl), —(C3-C5 cycloalkyl), -(phenyl), -(heteroalkyl), -(hydroxyalkyl), benzyl, -(alkyl)-(C3-C5 cycloalkyl), -(alkyl)-OH, -(alkyl)-O-(alkyl), —OH, —NH2, —OAc, —CN, OCF3, halogen, C(O)—NH2, —C(O)—NH-(alkyl), C(O)—NH-(phenyl), —O-alkyl, —O-alkenyl, —O-alkynyl, —O-phenyl, —NH-alkyl, —NH— alkenyl, —NH-alkynyl, —NH-phenyl, or —C(O)—N(alkyl)2; and
R5, R6, R7, R8 are each independently —H, —CN, —CF3, —OCF3, -(alkyl), -(alkenyl), -(alkynyl), -(phenyl), -(heteroalkyl), -(hydroxyalkyl), —NH2, —NH-(alkyl), —NH-(alkenyl), —NH-(alkynyl), —NH-(phenyl), —OH, —OAc, —CO2H, —CO2-(alkyl), —O—C(O)(alkyl), —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(phenyl), C(O)—NH2, C(O)—NH-(alkyl), or C(O)—NH-(phenyl),
or an enantiomer, racemic mixture, or a pharmaceutically acceptable salt thereof.