Himbacine

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Himbacine
Himbacine.svg
Clinical data
ATC code
  • none
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
ChEBI
ChEMBL
Chemical and physical data
Formula C22H35NO2
Molar mass 345.27 g/mol
3D model (JSmol)
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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]

References[edit]

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