Cannabinoid derivatives

Patent metadata

Field	Value
Publication number	US-12325709-B2
Application number	US-202017765856-A
Country	US
Kind code	B2
Filing date	Oct 2, 2020
Priority date	Oct 2, 2019
Publication date	Jun 10, 2025
Grant date	Jun 10, 2025

Abstract

This disclosure relates to cannabinoid derivatives of Formula (I), wherein R4 or R7 is a carboxamide group, pharmaceutical compositions comprising these compounds and methods of using the cannabinoid derivatives. These compounds are potential cannabinoid receptor inhibitors, including CB1 and CB2 receptors.

First claim

We claim:

1. A compound having structural formula:

or an enantiomer, diastereomer, racemate, or tautomer thereof, or a pharmaceutically acceptable salt, solvate or hydrate of the compound, enantiomer, diastereomer, racemate, or tautomer, wherein
the

 moiety is

R 1 is hydrogen, halo, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, —CO 2 H, —(C 0 -C 4 alkyl)-C(O)O(C 1 -C 6 alkyl), —(C 0 -C 4 alkyl)-OC(O)O—(C 1 -C 6 alkyl), —OR 1a , —(C 1 -C 4 alkyl)OR 1a , —SR 1a , —(C 1 -C 4 alkyl)SR 1a , —NR 1b R 1c , —(C 1 -C 4 alkyl)NR 1b R 1c , —(C 1 -C 4 alkyl)C(O)NR 1b R 1c , —(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, —(C 0 -C 4 alkyl)-heterocycloalkyl, or oxo when attached to a ring of appropriate saturation, wherein
R 1a , R 1b , and R 1c are independently hydrogen, C 1 -C 4 alkyl, or —C(O)(C 1 -C 4 ) alkyl;

R 2 is hydrogen, halo, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, —CO 2 H, —(C 0 -C 4 alkyl)-C(O)O(C 1 -C 6 alkyl), —(C 0 -C 4 alkyl)-OC(O)O—(C 1 -C 6 alkyl), —OR 2a , —(C 1 -C 4 alkyl)OR 2a , —SR 2a , —(C 1 -C 4 alkyl)SR 2a , —NR 2b R 2c , —(C 1 -C 4 alkyl)NR 2b R 2c , —(C 1 -C 4 alkyl)C(O)NR 2b R 2c , —(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, —(C 0 -C 4 alkyl)-heterocycloalkyl, or oxo when attached to a ring of appropriate saturation, wherein
R 2a , R 2b , and R 2c are independently hydrogen, C 1 -C 4 alkyl, or —C(O)(C 1 -C 4 ) alkyl;

R 3 is C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, —(OCH 2 CH 2 ) 0-6 O(C 1 -C 8 alkyl), —(C 0 -C 4 alkyl)-NR 3a R 3b , —(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl or —(C 0 -C 4 alkyl)-heterocycloalkyl, wherein R 3a and R 3b are each independently hydrogen or C 1 -C 6 alkyl;
R 4 is hydrogen,

 wherein
Q 1 is O or S;
R 4a is hydrogen, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, —OR 4c , —(C 1 , C 2 or C 4 alkyl)OR 4c , —(C 0 -C 4 alkyl)-C(O)(C 1 -C 4 alkyl), —(C 0 -C 4 alkyl)-C(O)O(R 4c ), —(C 0 -C 4 alkyl)CN, —(CH 2 CH 2 O) 0-6 (C 1 -C 8 alkyl), —(CH 2 CH 2 O) 3-6 (NR 4c R 4d ), (—C 1 , C 2 or C 4 alkyl)NR 4c R 4d , —(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, or —(C 0 , C 1 or C 4 alkyl)-heterocycloalkyl,
R 4b is hydrogen, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, —OR 4c , —(C 1 , C 2 or C 4 alkyl)OR 4c , —(C 0 -C 4 alkyl)-C(O)(C 1 -C 4 alkyl), —(C 0 -C 4 alkyl)-C(O)O(R 4c ), —(C 0 -C 4 alkyl)CN, —(CH 2 CH 2 O) 0-6 (C 1 -C 8 alkyl), —(CH 2 CH 2 O) 3-6 (NR 4c R 4d ), —(C 1 , C 2 or C 4 alkyl)NR 4c R 4d , —(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, or —(C 0 , C 1 or C 4 alkyl)-heterocycloalkyl,
wherein R 4c and R 4d are hydrogen or C 1 -C 6 alkyl,

or R 4a and R 4b together with a nitrogen to which they are attached form a heterocycloalkyl or heteroaryl ring,
R 4c is hydrogen, C 1 -C 8 alkyl, cycloalkyl or aryl,
R 4f is —OR 4g , C 1 -C 8 alkyl, cycloalkyl or NR 4h R 4i ,
wherein R 49 is C 1 -C 8 alkyl, cycloalkyl, or aryl, and
wherein R 4h and R 4i are C 1 -C 8 alkyl, or R 4h and R 4i together with a nitrogen to which they are attached form a heterocyloalkyl ring or heteroaryl ring, and

R 4j and R 4k are each independently hydrogen or C 1 -C 8 alkyl;

R 5 is hydrogen, C 1 -C 8 alkyl, —(C 1 -C 4 alkyl)-O—(C 1 -C 4 alkyl), —C(O)(C 1 -C 4 alkyl), —C(O)O(C 1 -C 4 alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 4 alkyl), —C(O)N(C 1 -C 4 alkyl) 2 , —(C 1 -C 4 alkyl)C(O)O(C 1 -C 4 alkyl), or —(C 1 -C 4 alkyl)OC(O)(C 1 -C 4 alkyl);
R 6 is —OR 6a , wherein R 6a is hydrogen, —(C 1 -C 4 alkyl)-O—(C 1 -C 4 alkyl), —C(O)(C 1 -C 4 alkyl), —C(O)O(C 1 -C 4 alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 4 alkyl), —C(O)N(C 1 -C 4 alkyl) 2 , —(C 1 -C 4 alkyl)C(O)O(C 1 -C 4 alkyl), or —(C 1 -C 4 alkyl)OC(O)(C 1 -C 4 alkyl); and
R 7 is hydrogen,

 provided R 7 is not hydrogen when R 4 is hydrogen, wherein
Q 2 is O or S;
R 7a is hydrogen, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, —OR 7c , —(C 1 -C 4 alkyl)OR 7c , —(C 0 -C 4 alkyl)-C(O)(C 1 -C 4 alkyl), —(C 0 -C 4 alkyl)-C(O)O(R 7c ), —(C 0 -C 4 alkyl)CN, —(CH 2 CH 2 O) 0-6 (C 1 -C 8 alkyl), —(CH 2 CH 2 O) 3-6 (NR 7c R 7d ), —(C 1 , C 2 or C 4 alkyl)NR 7c R 7d , —(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, or —(C 0 , C 1 or C 4 alkyl)-heterocycloalkyl,
R 7b is hydrogen, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, —OR 7c , —(C 1 -C 4 alkyl)OR 7c , —(C 0 -C 4 alkyl)-C(O)(C 1 -C 4 alkyl), —(C 0 -C 4 alkyl)-C(O)O(R 7c ), —(C 0 -C 4 alkyl)CN, —(CH 2 CH 2 O) 0-6 (C 1 -C 8 alkyl), —(CH 2 CH 2 O) 3-6 (NR 7c R 7d ), —(C 1 , C 2 or C 4 alkyl)NR 7c R 7d , —(C 0 -C 4 alkyl)-aryl, —(C 0 -C 4 alkyl)-heteroaryl, —(C 0 -C 4 alkyl)-cycloalkyl, or —(C 0 , C 1 or C 4 alkyl)-heterocycloalkyl,
wherein R 70 and R 7d are hydrogen or C 1 -C 6 alkyl,

or R 7a and R 7h together with a nitrogen to which they are attached form a heterocycloalkyl or heteroaryl ring,
R 7e is H, C 1 -C 8 alkyl, cycloalkyl, or aryl,
R 7f is —OR 7g , C 1 -C 8 alkyl, cycloalkyl, or NR 7h R 7i ,
wherein R 7g is C 1 -C 8 alkyl, cycloalkyl, or aryl, and
wherein R 7h and R 7i are C 1 -C 8 alkyl, or R 7h and R 7i together with a nitrogen to which they are attached form a heterocyloalkyl ring or heteroaryl ring, and

R 7j and R 7k are each independently hydrogen or C 1 -C 8 alkyl;

wherein
each alkyl, alkenyl and alkynyl is unsubstituted, halogenated, substituted with one hydroxyl group, one or two C 1 -C 6 alkoxy groups, one or two —C(O)O(C 1 -C 4 alkyl) groups, or one or two oxo groups;
each cycloalkyl has 3-10 ring carbons and is saturated or partially unsaturated, and optionally includes one or two fused cycloalkyl rings, each fused ring having 3-8 ring members, and is substituted with 0-6 R 8 ;
each heterocycloalkyl has 3-10 ring members and 1-3 heteroatoms where each is independently nitrogen, oxygen or sulfur and is saturated or partially unsaturated, and optionally includes one or two fused cycloalkyl rings, each having 3-8 ring members, and is substituted with 0-6 R 8 ;
each aryl is a phenyl or a naphthyl, and optionally includes one or two fused cycloalkyl or heterocycloalkyl rings, each fused cycloalkyl or heterocycloalkyl ring having 4-8 ring members, and is substituted with 0-5 R 9 ;
each heteroaryl is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms, where each is independently nitrogen, oxygen or sulfur or a 8-10 membered bicyclic heteroaryl having 1-5 heteroatoms where each is independently nitrogen, oxygen or sulfur, and optionally includes one or two fused cycloalkyl or heterocycloalkyl rings, each fused cycloalkyl or heterocycloalkyl ring having 4-8 ring members, and is substituted with 0-5 R 9 ,
in which
each R 8 is independently oxo, C 1 -C 4 alkyl, —Cl, —F, —Br, —CN, —SF 5 , —N 3 , nitro, —SR A , —S(O) 1-2 R A , —OR A , —(C 0 -C 3 alkyl)-OR B , —NR B R A , —C(O)R A , —C(O)NR B R A , —NR B C(O)R A , —C(S)NR B R A , —NR B C(S)R A , —CO 2 R A , —OC(O)R A , —C(O)SR A , —SC(O)R A , —C(S)OR A , —OC(S)R A , —C(S)SR A , —SC(S)R A , —S(O) 1-2 OR A , —OS(O) 1-2

Assignees

• Canopy Growth Corp

Inventors

• Ahmar Siawash
• Kim Jung Yun
• Lai Ping Shan
• Omeara Jeffrey Alan
• To Quang Huy
• Dove Peter Martin

Classifications

• C07D295/26

  Sulfur atoms · CPC title

• C07D295/192

  from aromatic carboxylic acids · CPC title

• C07D271/10

  1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles · CPC title

• C07D263/32

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07D261/14

  Nitrogen atoms · CPC title