| Title : ( R)- N-(1-Methyl-2-hydroxyethyl)-13-( S)-methyl-arachidonamide (AMG315): A Novel Chiral Potent Endocannabinoid Ligand with Stability to Metabolizing Enzymes - Liu_2018_J.Med.Chem_61_8639 |
| Author(s) : Liu Y , Ji L , Eno M , Kudalkar S , Li AL , Schimpgen M , Benchama O , Morales P , Xu S , Hurst D , Wu S , Mohammad KA , Wood JT , Zvonok N , Papahatjis DP , Zhou H , Honrao C , Mackie K , Reggio P , Hohmann AG , Marnett LJ , Makriyannis A , Nikas SP |
| Ref : Journal of Medicinal Chemistry , 61 :8639 , 2018 |
|
Abstract :
The synthesis of potent metabolically stable endocannabinoids is challenging. Here we report a chiral arachidonoyl ethanolamide (AEA) analogue, namely, (13 S,1' R)-dimethylanandamide (AMG315, 3a), a high affinity ligand for the CB1 receptor ( Ki of 7.8 +/- 1.4 nM) that behaves as a potent CB1 agonist in vitro (EC50 = 0.6 +/- 0.2 nM). (13 S,1' R)-dimethylanandamide is the first potent AEA analogue with significant stability for all endocannabinoid hydrolyzing enzymes as well as the oxidative enzymes COX-2. When tested in vivo using the CFA-induced inflammatory pain model, 3a behaved as a more potent analgesic when compared to endogenous AEA or its hydrolytically stable analogue AM356. This novel analogue will serve as a very useful endocannabinoid probe. |
| PubMedSearch : Liu_2018_J.Med.Chem_61_8639 |
| PubMedID: 30196704 |
Liu Y, Ji L, Eno M, Kudalkar S, Li AL, Schimpgen M, Benchama O, Morales P, Xu S, Hurst D, Wu S, Mohammad KA, Wood JT, Zvonok N, Papahatjis DP, Zhou H, Honrao C, Mackie K, Reggio P, Hohmann AG, Marnett LJ, Makriyannis A, Nikas SP (2018)
( R)- N-(1-Methyl-2-hydroxyethyl)-13-( S)-methyl-arachidonamide (AMG315): A Novel Chiral Potent Endocannabinoid Ligand with Stability to Metabolizing Enzymes
Journal of Medicinal Chemistry
61 :8639
Liu Y, Ji L, Eno M, Kudalkar S, Li AL, Schimpgen M, Benchama O, Morales P, Xu S, Hurst D, Wu S, Mohammad KA, Wood JT, Zvonok N, Papahatjis DP, Zhou H, Honrao C, Mackie K, Reggio P, Hohmann AG, Marnett LJ, Makriyannis A, Nikas SP (2018)
Journal of Medicinal Chemistry
61 :8639