258 P.H. Reggio
In the non-classical CBs, Melvin has also shown that the phenolic hydroxyl at
C-2′(see drawing of 2 ) is not necessary as 2′-deoxy-CP-55,940 ( 15 ) possessed a
Ki= 40.2 ± 13.5 nM at the CB 1 receptor (Melvin et al. 1993). In this case, however,
although CB 1 affinity is retained, the deoxy analog does have an attenuated affinity
relative to that of CP-55,940 ( 2 ) whose CB 1 Ki= 0.137 ± 0.038 nM. The affinity dif-
ference between 1-deoxy-11-hydroxy-∆^8 -THC-DMH ( 13 )and2′-deoxy-CP-55,940
( 15 ) may be due to the greater entropic expense incurred by 15 upon binding, as it
is a more flexible molecule.
Razdan and co-workers (Wiley et al. 2002) recently reported a series of resor-
cinol derivatives that exhibited varying affinities for CB 1 and CB 2. When the free
phenols at C1 and C3 in this series (with DMH side chains) were etherified, CB 2 -
selective compounds resulted [e.g., O-1966A ( 16 ), CB 1 Ki= 5,055 ± 984 nM; CB 2
Ki= 23 ± 2.1 nM]. These results are consistent with results reported by Mechoulam
and co-workers (Hanus et al. 1999) for HU-308 ( 17 ), which also has etherification
at the same positions as O-1966A and is highly CB 2 -selective (CB 1 Ki>10μM; CB 2
Ki= 22.7 ± 3.9 nM).