KM-233 explained

KM-233 is a synthetic cannabinoid drug which is a structural analog of Δ8-tetrahydrocannabinol (THC), the less active but more stable isomer of the active component of Cannabis. KM-233 differs from Δ8-THC by the pentyl side chain being replaced by a 1,1-dimethylbenzyl group. It has high binding affinity in vitro for both the CB₁ and CB₂ receptors, with a CB₂ affinity of 0.91 nM and 13-fold selectivity over the CB₁ receptor.^[1] In animal studies, it has been found to be a potential treatment for glioma, a form of brain tumor.^[2] Many related analogues are known where the 1,1-dimethylbenzyl group is substituted or replaced by other groups, with a fairly well established structure-activity relationship.^{[3] [4] [5] [6] [7]}

See also

• AM-411
• AMG-36

Notes and References

1. Krishnamurthy M, Ferreira AM, Moore BM . Synthesis and testing of novel phenyl substituted side-chain analogues of classical cannabinoids . Bioorganic & Medicinal Chemistry Letters . 13 . 20 . 3487–90 . October 2003 . 14505654 . 10.1016/s0960-894x(03)00729-7 .
2. Duntsch C, Divi MK, Jones T, Zhou Q, Krishnamurthy M, Boehm P, Wood G, Sills A, Moore BM . 6 . Safety and efficacy of a novel cannabinoid chemotherapeutic, KM-233, for the treatment of high-grade glioma . Journal of Neuro-Oncology . 77 . 2 . 143–52 . April 2006 . 16314952 . 10.1007/s11060-005-9031-y . 27299940 .
3. Nadipuram AK, Krishnamurthy M, Ferreira AM, Li W, Moore BM . Synthesis and testing of novel classical cannabinoids: exploring the side chain ligand binding pocket of the CB1 and CB2 receptors . Bioorganic & Medicinal Chemistry . 11 . 14 . 3121–32 . July 2003 . 12818675 . 10.1016/s0968-0896(03)00238-4 .
4. Durdagi S, Kapou A, Kourouli T, Andreou T, Nikas SP, Nahmias VR, Papahatjis DP, Papadopoulos MG, Mavromoustakos T . 6 . The application of 3D-QSAR studies for novel cannabinoid ligands substituted at the C1' position of the alkyl side chain on the structural requirements for binding to cannabinoid receptors CB1 and CB2 . Journal of Medicinal Chemistry . 50 . 12 . 2875–85 . June 2007 . 17521177 . 10.1021/jm0610705 .
5. Krishnamurthy M, Gurley S, Moore BM . Exploring the substituent effects on a novel series of C1'-dimethyl-aryl Delta8-tetrahydrocannabinol analogs . Bioorganic & Medicinal Chemistry . 16 . 13 . 6489–500 . July 2008 . 18524604 . 10.1016/j.bmc.2008.05.034 .
6. Ferreira AM, Krishnamurthy M, Moore BM, Finkelstein D, Bashford D . Quantitative structure-activity relationship (QSAR) for a series of novel cannabinoid derivatives using descriptors derived from semi-empirical quantum-chemical calculations . Bioorganic & Medicinal Chemistry . 17 . 6 . 2598–606 . March 2009 . 19250829 . 10.1016/j.bmc.2008.11.059 .
7. Brogi S, Corelli F, Di Marzo V, Ligresti A, Mugnaini C, Pasquini S, Tafi A . Three-dimensional quantitative structure-selectivity relationships analysis guided rational design of a highly selective ligand for the cannabinoid receptor 2 . European Journal of Medicinal Chemistry . 46 . 2 . 547–55 . February 2011 . 21183257 . 10.1016/j.ejmech.2010.11.034 .