Himbacine Explained

Himbacine is an alkaloid isolated from the bark of Australian magnolias. Himbacine has been synthesized using a Diels-Alder reaction as a key step.^[1] Himbacine's activity as a muscarinic receptor antagonist, with specificity for the muscarinic acetylcholine receptor M2, made it a promising starting point in Alzheimer's disease research.^{[2] [3]} The development of a muscarinic antagonist based on himbacine failed but an analog, vorapaxar, has been approved by the FDA as a thrombin receptor antagonist.^{[4] [5]}

Notes and References

1. Chackalamannil S, Davies RJ, Wang Y, etal . Total Synthesis of (+)-Himbacine and (+)-Himbeline . J. Org. Chem. . 64 . 6 . 1932–1940 . March 1999 . 11674285. 10.1021/jo981983+.
2. 10.1016/0960-894X(94)00459-S . Malaska MJ, Fauq AH, Kozikowski AP, Aagaard PJ, McKinney M . Chemical Modification of Ring C of Himbacine: Discovery of a Pharmacophoric Element for M2-Selectivity . Bioorganic & Medicinal Chemistry Letters . 5 . 1 . 61–66 . 1995.
3. Chackalamannil S, Doller D, McQuade R, Ruperto V . Himbacine analogs as muscarinic receptor antagonists-effects of tether and heterocyclic variations . Bioorganic & Medicinal Chemistry Letters . 14 . 3967–3970 . 2004 . 15225708 . 10.1016/j.bmcl.2004.05.047 . 15.
4. Chackalamannil S, Wang Y, Greenlee WJ, etal . Discovery of a Novel, Orally Active Himbacine-Based Thrombin Receptor Antagonist (SCH 530348) with Potent Antiplatelet Activity . J. Med. Chem. . 51 . 3061–3064 . 2008 . 18447380. 10.1021/jm800180e . 11.
5. Web site: Blog entry about Himbacine and its history in drug development . 13 May 2008 . 2016-08-11.