Himbacine

Himbacine

Systematic (IUPAC) name
(3aR,4R,4aS,8aR,9aS)- 4-{(E)-[(2R,6S)- 1,6-dimethylpiperidin- 2-yl]vinyl}- 3-methyldecahydronaphtho[2,3-c]furan- 1(3H)-one
Identifiers
CAS Number	6879-74-9
ATC code	none
PubChem	CID 6436265
IUPHAR/BPS	324
ChemSpider	4940913
ChEBI	CHEBI:5720
ChEMBL	CHEMBL277642
Chemical data
Formula	C22H35NO2
Molar mass	345.27 g/mol
SMILES O=C3O[C@H]([C@@H]4[C@H](/C=C/[C@@H]1N(C)[C@@H](C)CCC1)[C@@H]2[C@H](CCCC2)C[C@H]34)C
InChI InChI=1S/C22H35NO2/c1-14-7-6-9-17(23(14)3)11-12-19-18-10-5-4-8-16(18)13-20-21(19)15(2)25-22(20)24/h11-12,14-21H,4-10,13H2,1-3H3/b12-11+/t14-,15-,16+,17+,18-,19+,20-,21+/m0/s1 Key:FMPNFDSPHNUFOS-LPJDIUFZSA-N
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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".