(R)-[(2S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl](6-methoxyquinolin-4-yl)methanol

• ChemBase ID: 351
• Molecular Formular: C20H24N2O2
• Molecular Mass: 324.41676
• Monoisotopic Mass: 324.18377802
• SMILES: O[C@@H]([C@H]1N2C[C@@H](C(C1)CC2)C=C)c1c2c(ncc1)ccc(OC)c2
• Canonical SMILES: C=C[C@H]1CN2CCC1C[C@H]2[C@@H](c1ccnc2c1cc(OC)cc2)O
• InChI: InChI=1S/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3/t13-,14?,19-,20+/m0/s1
• InChIKey: LOUPRKONTZGTKE-VOMFEXJBSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (R)-[(2S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl](6-methoxyquinolin-4-yl)methanol
• IUPAC Traditional name: quinine
• Brand Name: Aflukin; Chinin; Chinine; Coco-Quinine; None; Quinine Dab
• Synonyms: 6'-Methoxycinchonidine; 6'-Methoxycinchonine; Quinine, Anhydrous; Quinineanhydrous; Quinoline Alkaloid; Quinine sulfate; Quinine; (1R)-(6-methoxyquinolin-4-yl)((2S,5R)-5-vinylquinuclidin-2-yl)methanol

Database IDs

• CAS Number: 130-95-0
• PubChem SID: 160963814
• PubChem CID: 8549

CALCULATED PROPERTIES

JChem

• Acid pKa: 13.892048
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): -0.7213722
• LogD (pH = 7.4): 0.863951
• Log P: 2.513464
• Molar Refractivity: 94.6936 cm^3
• Polarizability: 38.350784 Å^3
• Polar Surface Area: 45.59 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.82
• LOG S: -2.99
• Solubility (Water): 3.34e-01 g/l

PROPERTIES

Physical Property

• Solubility: 500 mg/L
• Hydrophobicity(logP): 2.6

DETAILS

DrugBank - DB00468

• Drug Groups: approved
• Description: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [PubChem]
• Indication: For the treatment of malaria and leg cramps
• Pharmacology: Quinine is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. Quinine acts as a blood schizonticide although it also has gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is thought to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine.
• Toxicity: Quinine is a documented causative agent of drug induced thrombocytopenia (DIT). Thrombocytopenia is a low amount of platelets in the blood. Quinine induces production of antibodies against glycoprotein (GP) Ib-IX complex in the majority of cases of DIT, or more rarely, the platelet-glycoprotein complex GPIIb-IIIa. Increased antibodies against these complexes increases platelet clearance, leading to the observed thrombocytopenia.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic, over 80% metabolized by the liver.
• Absorption: 76 - 88%
• Half Life: Approximately 18 hours
• Protein Binding: Approximately 70%
• Elimination: Quinine is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in urine.
• Distribution: * 1.43 ± 0.18 L/kg [Healthy Pediatric Controls]; * 0.87 ± 0.12 L/kg [P. falciparum Malaria Pediatric Patients]; * 2.5 to 7.1 L/kg [healthy subjects who received a single oral 600 mg dose]
• Clearance: * 0.17 L/h/kg [healthy]; * 0.09 L/h/kg [patients with uncomplicated malaria]; * 18.4 L/h [healthy adult subjects with administration of multiple-dose activated charcoal]; * 11.8 L/h [healthy adult subjects without administration of multiple-dose activated charcoal]; * Oral cl=0.06 L/h/kg [elderly subjects]
• References: Paintaud G, Alvan G, Berninger E, Gustafsson LL, Idrizbegovic E, Karlsson KK, Wakelkamp M: The concentration-effect relationship of quinine-induced hearing impairment. Clin Pharmacol Ther. 1994 Mar;55(3):317-23. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Paintaud G, Alvan G, Berninger E, Gustafsson LL, Idrizbegovic E, Karlsson KK, Wakelkamp M: The concentration-effect relationship of quinine-induced hearing impairment. Clin Pharmacol Ther. 1994 Mar;55(3):317-23. Pubmed