| Stereochemistry | ACHIRAL |
| Molecular Formula | C23H24Cl2N2O3 |
| Molecular Weight | 447.354 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC=C2N(C(=O)C3=CC=CC(Cl)=C3Cl)C(C)=C(CCN4CCOCC4)C2=C1
InChI
InChIKey=FSFZRNZSZYDVLI-UHFFFAOYSA-N
InChI=1S/C23H24Cl2N2O3/c1-15-17(8-9-26-10-12-30-13-11-26)19-14-16(29-2)6-7-21(19)27(15)23(28)18-4-3-5-20(24)22(18)25/h3-7,14H,8-13H2,1-2H3
| Molecular Formula | C23H24Cl2N2O3 |
| Molecular Weight | 447.354 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
L-768242 (GW-405,833) is a potent and selective partial agonist for the cannabinoid CB2 receptor with marked anti-inflammatory and anti-hyperalgesic activity in high doses. L-768242 suppresses pathological pain in preclinical models without unwanted central side effects of CB1 agonists. L-768242 dose-dependently reversed established mechanical allodynia in models of neuropathic (i.e. partial sciatic nerve ligation (PSNL) model) and inflammatory (i.e. complete Freund's adjuvant (CFA) model) pain. Despite substantial penetration to the CNS L-768242 did not produce cannabimimetic deficits below doses of 100 mg/kg i.p. Anti-allodynic efficacy of L-768242 was opioid-independent as systemic administration of naltrexone did not block the anti-hyperalgesic or antinociceptive effects of L-768242. In in vitro studies, L-768242 was reported to behave as a partial agonist at human CB2 receptors and, alternately, a potent inverse agonist at both human and rat CB2 receptors and a weak agonist at rat CB1 receptors. L-768242 was suggested to act as a non-competitive CB1 antagonist as L-768242 non-competitively antagonized CP55,940-induced adenylyl cyclase activity, ERK1/2 phosphorylation, PIP2 signaling and CB1 internalization in vitro in HEK cells transfected with CB1 and showed a complex, time-dependent effect on arrestin recruitment in CHO cells. Anti-allodynic efficacy of L-768242 is CB1-dependent but does not seem to involve engagement of the CB1 receptor’s orthosteric site.
CNS Activity
Originator
Approval Year
PubMed
Patents
Sample Use Guides
Mice of both sexes were treatment i.p. with L-152,804 at a doses 3, 10, and 30 mg/kg as a single dose
Route of Administration:
Intraperitoneal
Mouse and rat spleen tissue were embedded in TissueTek and cut into 20 μm thick sections on a cryostat. The slices were absorbed on SuperFrost Plus slides (Menzel) and stored at −80 °C until use. For the experiment, the slices were thawed on ice for 10 min before conditioning in incubation buffer (50 mM Tris/HCl, 5% BSA, pH 7.4) on ice for 10 min. Excess solution was carefully removed, and the tissue slices were dried for 10 min. The slices were then dripped with 600 μL of incubation buffer containing 0.2 nM 16 and incubated for 15 min at rt in a humid chamber. For blockade conditions, the slices were dripped with 600 μL of a mixture of radioligand (0.2 nM) and 17 (5 μM). After incubation, the slices were washed with washing buffer (50 mM Tris/HCl, 1% BSA, 5% EtOH, pH 7.4) for 2 min (2×) and distilled water for 5 s (2×) on ice. After drying, the slices were exposed (30 min) to appropriate phosphor imager plates (Fuji) and the films were scanned in a BAS5000 reader (Fuji).
