conessine   Click here for help

GtoPdb Ligand ID: 8981

Comment: Conessine is an alkaloid obtained from the bark and seeds of Holarrhena antidysenterica trees. It binds with high affinity to rat and human histamine H3 receptors in radio-ligand binding assays, acting as a receptor antagonist [2-3]. H3 antagonists are being researched as potential drugs for the treatment of neurodegenerative conditions and for their stimulant and nootropic effects. For example, pitolisant is in clinical trial for Parkinson's disease, narcolepsy, cataplexy and excessive daytime sleepiness.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 2
Hydrogen bond donors 0
Rotatable bonds 1
Topological polar surface area 6.48
Molecular weight 356.32
XLogP 5
No. Lipinski's rules broken 0
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Isomeric SMILES CN([C@H]1CC[C@]2(C(=CC[C@@H]3[C@@H]2CC[C@]24[C@H]3CC[C@@H]4[C@@H](N(C2)C)C)C1)C)C
InChI InChI=1S/C24H40N2/c1-16-20-8-9-22-19-7-6-17-14-18(25(3)4)10-12-23(17,2)21(19)11-13-24(20,22)15-26(16)5/h6,16,18-22H,7-15H2,1-5H3/t16-,18-,19+,20+,21-,22-,23-,24-/m0/s1
1. Panula P, Chazot PL, Cowart M, Gutzmer R, Leurs R, Liu WL, Stark H, Thurmond RL, Haas HL. (2015)
International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors.
Pharmacol Rev, 67 (3): 601-55. [PMID:26084539]
2. Santora VJ, Covel JA, Hayashi R, Hofilena BJ, Ibarra JB, Pulley MD, Weinhouse MI, Sengupta D, Duffield JJ, Semple G et al.. (2008)
A new family of H3 receptor antagonists based on the natural product Conessine.
Bioorg Med Chem Lett, 18 (4): 1490-4. [PMID:18194865]
3. Zhao C, Sun M, Bennani YL, Gopalakrishnan SM, Witte DG, Miller TR, Krueger KM, Browman KE, Thiffault C, Wetter J et al.. (2008)
The alkaloid conessine and analogues as potent histamine H3 receptor antagonists.
J Med Chem, 51 (17): 5423-30. [PMID:18683917]