Himbacine

Himbacine

Himbacine is an alkaloid isolated from the bark of Australian magnolias. Himbacine has been synthesized using a Diels-Alder reaction as a key step.<ref name="pmid11674285">Chackalamannil S, Davies RJ, Wang Y, et al.,

 Total Synthesis of (+)-Himbacine and (+)-Himbeline, 
 J. Org. Chem., 
 
 Vol. 64(Issue: 6),
 pp. 1932–1940,
 DOI: 10.1021/jo981983+,
 PMID: 11674285,</ref> 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.<ref name="Malaska et al">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 and Medicinal Chemistry Letters, 
 1995,
 Vol. 5(Issue: 1),
 pp. 61–66,
 DOI: 10.1016/0960-894X(94)00459-S,</ref><ref name="pmid15225708">Chackalamannil S, Doller D, McQuade R, Ruperto V, 
 Himbacine analogs as muscarinic receptor antagonists-effects of tether and heterocyclic variations, 
 Bioorganic and Medicinal Chemistry Letters, 
 2004,
 Vol. 14(Issue: 15),
 pp. 3967–3970,
 DOI: 10.1016/j.bmcl.2004.05.047,
 PMID: 15225708,</ref>  The development of a muscarinic antagonist based on Himbacine failed but an analog is now in clinical trials as a thrombin receptor antagonist.<ref name="pmid18447380">Chackalamannil S, Wang Y, Greenlee WJ, 'et al., 
 Discovery of a Novel, Orally Active Himbacine-Based Thrombin Receptor Antagonist (SCH 530348) with Potent Antiplatelet Activity, 
 J. Med. Chem., 
 2008,
 Vol. 51(Issue: 11),
 pp. 3061–3064,
 DOI: 10.1021/jm800180e,
 PMID: 18447380,</ref><ref name="urlIn Which I Hate A Wonder Drug. In the Pipeline:">

Blog entry about Himbacine and its history in drug development(link). {{{website}}}.

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See also

• Vorapaxar

References

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