Anandamide analogues

The first substrate analogue inhibitors of FAAH were reported in 1994. The anandamide analogues prepared represented three elasses of putative transition-state inhibitors a-trifluoromethyl ketones, a-ketoesters and a-ketoamides [62], In the initial sereening studies, it was found that the trifluoromethyl ketone eompounds tested were effeetive inhibitors of AEA hydrolysis. A selected set of a-keto esters also inhibited hydrolysis, while a-keto amides were ineffective. In particular, arachidonyl trifluoromethyl ketone (32), gave almost 100% inhibition of anandamide hydrolysis. A detailed investigation of the structural requirements for FAAH inhibition with a-trifluoromethyl ketones has been carried out by Roger and co-workers [63]. 

Lewis DY, Brett RR (2010) Activity-based anorexia in C57/BL6 mice effects of the phytocannabinoid, Delta9-tetrahydrocatmabinol (THC) and the anandamide analogue, OMDM-2. Eur Neutopsychopharm 20 622... 

Figure 5. Anandamide analogues acting as cannabinoid receptor agonists.

Some examples of anandamide analogues (AM356, chloroanandamide and ACPA) are presented in Figure 5. A detailed discussion of the structure-activity relationships of anandamide analogues is summarized elsewhere (Khanolkar and Makriyannis, 1999). It should be noted that ... 

Bisogno T, Hanus L, De Petrocellis L, TchUibon S, Ponde DE, Brandi I, Moriello AS, Davis JB, Mechoulam R, Di Marzo V (2001) Molecular targets for cannabidiol and its synthetic analogues effect on vanilloid VRl receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol 134 845-852... 

Jarrahian A, Manna S, Edgemond WS, Campbell WB, Hillard CJ (2000) Structure-activity relationships among N-arachidonylethanolamine (anandamide) head group analogues for the anandamide transporter. J Neurochem 74 2597-2606... 

Lin S, Khanolkar AD, Fan P, Goutopoulos A, Qin C, Papahadjis D, Makriyannis A (1998) Novel analogues of arachidonylethanolamide (anandamide) affinities for the CBl and CB2 cannabinoid receptors and metabolic stability. J Med Chem 41 5353-5361... 

Ross RA, Gibson TM, Brockie HC, Leslie M, Pashmi G, Craib SJ, Di Marzo V, Pertwee RG (2001) Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens. Br J Pharmacol 132 631-640... 

A series of MAFP analogues, one of which, 0-1624, is quite potent and selective vs CBi receptors and was found to enhance anandamide levels after intrathecal administration to mice (Martin et al. 2000). 

Fowler CJ, Tiger G, Lopez-Rodriguez ML, Viso A, Ortega-Gutierrez S, Ramos JA (2003) Inhibition of fatty acid amidohydrolase, the enzyme responsible for the metabolism of the endocannabinoid anandamide, by analogues of arachidonoyl-serotonin. J Enzyme Inhib Med Chem 18 225-231... 

Barnett-Norris J, Guarnieri F, Hurst DP, Reggio PH (1998) Exploration of biologically relevant conformations of anandamide, 2-arachidonylglycerol, and their analogues using conformational memories. J Med Chem 41 4861-4872... 

Ng EW, Aung MM, Abood ME, Martin BR, Razdan RK (1999) Unique analogues of anandamide arachidonyl ethers and carbamates and norarachidonyl carbamates and ureas. J Med Chem 42 1975-1981... 

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