himbacine

{{Short description|Chemical compound}}

{{Drugbox

| verifiedrevid = 407836401

| 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

| image = Himbacine.svg

| tradename =

| pregnancy_category =

| legal_status =

| routes_of_administration =

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 6879-74-9

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = M17C7V122D

| ATC_prefix = none

| ATC_suffix =

| PubChem = 6436265

| IUPHAR_ligand = 324

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 4940913

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 5720

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 277642

| C=22 | H=35 | N=1 | O=2

| 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

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = FMPNFDSPHNUFOS-LPJDIUFZSA-N

}}

Himbacine is an alkaloid isolated from the bark of Australian magnolias. Himbacine has been synthesized using a Diels-Alder reaction as a key step.{{cite journal |vauthors=Chackalamannil S, Davies RJ, Wang Y, etal |title=Total Synthesis of (+)-Himbacine and (+)-Himbeline |journal=J. Org. Chem. |volume=64 |issue=6 |pages=1932–1940 |date=March 1999 |pmid=11674285|doi=10.1021/jo981983+}} 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.{{cite journal |doi=10.1016/0960-894X(94)00459-S |vauthors=Malaska MJ, Fauq AH, Kozikowski AP, Aagaard PJ, McKinney M |title=Chemical Modification of Ring C of Himbacine: Discovery of a Pharmacophoric Element for M2-Selectivity |journal= Bioorganic & Medicinal Chemistry Letters |volume=5 |issue=1 |pages=61–66 |year=1995}}{{cite journal |vauthors=Chackalamannil S, Doller D, McQuade R, Ruperto V |title=Himbacine analogs as muscarinic receptor antagonists-effects of tether and heterocyclic variations |journal=Bioorganic & Medicinal Chemistry Letters |volume=14 |pages=3967–3970 |year=2004 |pmid=15225708 |doi=10.1016/j.bmcl.2004.05.047 |issue=15}} 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.{{cite journal |vauthors=Chackalamannil S, Wang Y, Greenlee WJ, etal |title=Discovery of a Novel, Orally Active Himbacine-Based Thrombin Receptor Antagonist (SCH 530348) with Potent Antiplatelet Activity |journal=J. Med. Chem. |volume=51 |pages=3061–3064 |year=2008 |pmid=18447380|doi=10.1021/jm800180e |issue=11}}{{cite web |url=http://blogs.sciencemag.org/pipeline/in_which_i_hate_a_wonder_drug |title=Blog entry about Himbacine and its history in drug development |date=13 May 2008 |access-date=2016-08-11}}