Himbacine

Himbacine
Clinical data
ATC code none
Identifiers
CAS Number 6879-74-9 YesY
PubChem (CID) 6436265
IUPHAR/BPS 324
ChemSpider 4940913 YesY
ChEBI CHEBI:5720 YesY
ChEMBL CHEMBL277642 YesY
Chemical and physical data
Formula C22H35NO2
Molar mass 345.27 g/mol
3D model (Jmol) Interactive image
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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

  1. ↑ Chackalamannil S, Davies RJ, Wang Y, et al. (March 1999). "Total Synthesis of (+)-Himbacine and (+)-Himbeline". J. Org. Chem. 64 (6): 1932–1940. doi:10.1021/jo981983+. PMID 11674285.
  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. doi:10.1016/j.bmcl.2004.05.047. PMID 15225708.
  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. doi:10.1021/jm800180e. PMID 18447380.
  5. ↑ "Blog entry about Himbacine and its history in drug development". Retrieved 2016-08-11.


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