A Theoretical Study of the Relationships between Electronic Structure and CB1 and CB2 Cannabinoid Receptor Binding Affinity in a Group of 1-Aryl-5-(1-H-pyrrol-1-yl)-1-H-pyrazole-3-carboxamides

Table 2

Molecules and their experimental binding affinities.

Molecule	R1	R1′	R1′′	R2	R3	R3′	log𝑘 (hCB1)	log𝑘 (hCB2)
1	-Cl	-Cl	-H	4-Chlorophenyl	-H	-H	2.08	1.90
2	-Cl	-Cl	-H	4-Chlorobenzyl	-H	-H	2.15	2.97
3	-Cl	-Cl	-H	2-Bromo-3,4,5-trimethoxybenzyl	-H	-H	2.36	—
4	-Cl	-Cl	-H	(4-Chlorophenyl)ethyl	-H	-H	1.85	—
5	-Cl	-Cl	-H	(3,4-Dichlorophenyl)ethyl	-H	-H	2.20	—
6	-Cl	-Cl	-H	(3-Chloro-4-methoxyphenyl)ethyl	-H	-H	2.57	3.46
7	-Cl	-Cl	-H	(2,4-Dichlorophenyl)ethyl	-H	-H	2.34	—
8	-Cl	-Cl	-H	Cyclopentyl	-H	-H	1.92	2.23
9	-Cl	-Cl	-H	Cycloheptyl	-H	-H	1.30	1.30
10	-Cl	-Cl	-H	4-Chlorophenyl	-Me	-Me	1.98	—
11	-Cl	-Cl	-H	4-Chlorobenzyl	-Me	-Me	1.95	—
12	-Cl	-Cl	-H	2-Bromo-3,4,5-trimethoxybenzyl	-Me	-Me	2.16	2.74
13	-Cl	-Cl	-H	(4-Chlorophenyl)ethyl	-Me	-Me	1.48	—
14	-Cl	-Cl	-H	(3,4-Dichlorophenyl)ethyl	-Me	-Me	2.07	—
15	-Cl	-Cl	-H	(3-Chloro-4-methoxyphenyl)ethyl	-Me	-Me	2.05	3.54
16	-Cl	-Cl	-H	(2,4-Dichlorophenyl)ethyl	-Me	-Me	2.19	—
17	-Cl	-Cl	-H	Cyclopentyl	-Me	-Me	2.18	2.49
18	-Cl	-Cl	-H	Cycloheptyl	-Me	-Me	1.90	1.90
19	-H	-Cl	-Cl	4-Chlorophenyl	-H	-H	3.11	2.90
20	-H	-Cl	-Cl	4-Chlorobenzyl	-H	-H	1.85	2.00
21	-H	-Cl	-Cl	(4-Chlorophenyl)ethyl	-H	-H	2.38	3.08
22	-H	-Cl	-Cl	Cyclopentyl	-H	-H	1.70	1.08
23	-H	-Cl	-Cl	Cycloheptyl	-H	-H	0.75	0.11
24	-H	-Cl	-Cl	Adamant-1-yl	-H	-H	1.49	1.30
25	-H	-Cl	-Cl	4-Chlorobenzyl	-Me	-Me	2.00	2.90
26	-H	-Cl	-Cl	(4-Chlorophenyl)ethyl	-Me	-Me	2.59	—
27	-H	-Cl	-Cl	Cyclopentyl	-Me	-Me	1.56	1.08
28	-H	-Cl	-Cl	Cycloheptyl	-Me	-Me	1.08	0.62
29	-H	-Cl	-Cl	Adamant-1-yl	-Me	-Me	0.75	1.08
30	-F	-F	-H	4-Chlorophenyl	-H	-H	3.32	—
31	-F	-F	-H	4-Chlorobenzyl	-H	-H	2.53	3.53
32	-F	-F	-H	2-Bromo-3,4,5-trimethoxybenzyl	-H	-H	2.54	—
33	-F	-F	-H	(4-Chlorophenyl)ethyl	-H	-H	1.90	—
34	-F	-F	-H	(3,4-Dichlorophenyl)ethyl	-H	-H	2.49	3.11
35	-F	-F	-H	(3-Chloro-4-methoxyphenyl)ethyl	-H	-H	2.98	3.29
36	-F	-F	-H	(2,4-Dichlorophenyl)ethyl	-H	-H	2.58	2.82
37	-F	-F	-H	Cyclopentyl	-H	-H	3.38	3.04
38	-F	-F	-H	Cycloheptyl	-H	-H	2.75	2.30
39	-F	-F	-H	4-Chlorophenyl	-Me	-Me	2.75	—
40	-F	-F	-H	4-Chlorobenzyl	-Me	-Me	1.75	—
41	-F	-F	-H	2-Bromo-3,4,5-trimethoxybenzyl	-Me	-Me	2.22	—
42	-F	-F	-H	(4-Chlorophenyl)ethyl	-Me	-Me	1.70	—
43	-F	-F	-H	(3,4-Dichlorophenyl)ethyl	-Me	-Me	1.73	—
44	-F	-F	-H	(3-Chloro-4-methoxyphenyl)ethyl	-Me	-Me	2.00	—
45	-F	-F	-H	(2,4-Dichlorophenyl)ethyl	-Me	-Me	1.61	2.86
46	-F	-F	-H	Cyclopentyl	-Me	-Me	2.92	2.95
47	-F	-F	-H	Cycloheptyl	-Me	-Me	1.75	2.04