US 11,787,772 B2
Carboxylic diarythiazepineamines as mixed mu- and delta-opioid receptor agonists
Andrew Kruegel, New York, NY (US); Dalibor Sames, New York, NY (US); and Jonathan A. Javitch, Dobbs Ferry, NY (US)
Assigned to THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, New York, NY (US)
Appl. No. 16/493,992
Filed by Andrew Kruegel, New York, NY (US); Dalibor Sames, New York, NY (US); and Jonathan A. Javitch, Dobbs Ferry, NY (US)
PCT Filed Mar. 15, 2018, PCT No. PCT/US2018/022650
§ 371(c)(1), (2) Date Sep. 13, 2019,
PCT Pub. No. WO2018/170275, PCT Pub. Date Sep. 20, 2018.
Claims priority of provisional application 62/471,745, filed on Mar. 15, 2017.
Prior Publication US 2020/0079745 A1, Mar. 12, 2020
Int. Cl. C07D 281/02 (2006.01); A61K 31/485 (2006.01); A61K 31/55 (2006.01); A61K 45/06 (2006.01)
CPC C07D 281/02 (2013.01) [A61K 31/485 (2013.01); A61K 31/55 (2013.01); A61K 45/06 (2013.01)] 23 Claims
 
1. A compound having the structure:

OG Complex Work Unit Chemistry
wherein
R1 is —H or -(alkyl);
R2 is —(C3-C20 alkyl)-CO2H or —(C3-C20 alkyl)-CO2-(alkyl);
R3 is —H or -(alkyl);
R4, R5, R6 and R7 are each independently —H, —Cl, —Br, —F, —I, —CN, —CF3, —OCF3, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), —NH2, —NH-(alkyl), —NH-(alkenyl), —NH-(alkynyl) —NH-(aryl), —NH-(heteroaryl), —OH, —OAc, —O—C(O) (alkyl), —O-(alkyl), —O-(alkylaryl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), —S-(heteroaryl), —S(O)-(alkyl), —S(O)-(aryl), —S(O)-(heteroaryl), —SO2-(alkyl), —SO2-(aryl), or —SO2-(heteroaryl);
R8, R9, —R10 and —R11 are each independently —H, —Cl, —Br, —F, —I, —CN, —CF3, —OCF3, -(alkyl), -(aryl), -(heteroaryl) -(alkenyl), -(alkynyl), —NH2, —NH-(alkyl), —NH-(alkenyl), —NH-(alkynyl) —NH-(aryl), —NH-(heteroaryl), —OH, —OAc, —O—C(O)(alkyl), —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), —S-(heteroaryl), —S(O)-(alkyl), —S(O)-(aryl), —S(O)-(heteroaryl), —SO2-(alkyl), —SO2-(aryl), or —SO2-(heteroaryl);
wherein when R2 is —(C3-6 alkyl)-CO2H, then one of R5 or R6 is -(alkynyl) or —S-(alkyl), or R5 and R6 are each independently —Cl, —Br, —F, or —I,
wherein when R2 is —(C3-6 alkyl)-CO2-(alkyl), then one of R5 or R6 is -(alkynyl), or R5 and R6 are each independently —Cl, —Br, —F, or —I, and
wherein when R1 is —CH3, R3, R4, R6, R7, R8, R9, —R10 and —R11 are each —H, and R5 is Cl, then R2 is other than —(CH2)7CO2H, —(CH2)10CO2H, —CH(CH3)(CH2)5CO2H or —(CH2)2CH(CH3)(CH2)3CO2H, and
wherein when R1 is —CH3, R3, R4, R6, R7, R8, R9, —R10 and —R11 are each —H, and R5 is SCH3, then R2 is other than —(CH2)6CO2H,
or a pharmaceutically acceptable salt or ester thereof.