(3R)-10-oxo-8-azatricyclo[5.3.1.0^{3,8}]undecan-5-yl 1H-indole-3-carboxylate

• ChemBase ID: 637
• Molecular Formular: C19H20N2O3
• Molecular Mass: 324.3737
• Monoisotopic Mass: 324.14739251
• SMILES: O(C1CC2N3[C@H](CC(C2)C(=O)C3)C1)C(=O)c1c2c([nH]c1)cccc2
• Canonical SMILES: O=C1CN2C3CC1C[C@@H]2CC(C3)OC(=O)c1c[nH]c2c1cccc2
• InChI: InChI=1S/C19H20N2O3/c22-18-10-21-12-5-11(18)6-13(21)8-14(7-12)24-19(23)16-9-20-17-4-2-1-3-15(16)17/h1-4,9,11-14,20H,5-8,10H2/t11?,12-,13?,14?/m1/s1
• InChIKey: UKTAZPQNNNJVKR-DBBXXEFVSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (3R)-10-oxo-8-azatricyclo[5.3.1.0^{3,8}]undecan-5-yl 1H-indole-3-carboxylate
• IUPAC Traditional name: dolasetron
• Brand Name: Anzemet; Dolasetronum [INN-Latin]; Dolasteron
• Synonyms: Dolasetron

Database IDs

• CAS Number: 115956-12-2
• PubChem SID: 160964100; 46505209
• PubChem CID: 60654

CALCULATED PROPERTIES

JChem

• Acid pKa: 12.182263
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 1.923664
• LogD (pH = 7.4): 2.3176217
• Log P: 2.3258903
• Molar Refractivity: 89.3352 cm^3
• Polarizability: 35.947193 Å^3
• Polar Surface Area: 62.4 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.41
• LOG S: -3.09
• Solubility (Water): 2.61e-01 g/l

PROPERTIES

Physical Property

• Solubility: Freely soluble in water
• Hydrophobicity(logP): 2.1

DETAILS

DrugBank - DB00757

• Drug Groups: approved
• Description: Dolasetron is an antinauseant and antiemetic agent indicated for the prevention of nausea and vomiting associated with moderately-emetogenic cancer chemotherapy and for the prevention of postoperative nausea and vomiting. Dolasetron is a highly specific and selective serotonin 5-HT3 receptor antagonist. This drug has not shown to have activity at other known serotonin receptors, and has low affinity for dopamine receptors.
• Indication: For the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, including initial and repeat courses of chemotherapy. Also used for the prevention of postoperative nausea and vomiting. This drug can be used intravenously for the treatment of postoperative nausea and vomiting.
• Pharmacology: Dolasetron is a highly specific and selective serotonin 5-HT₃ receptor antagonist, not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors. It is structurally and pharmacologically related to other 5-HT₃ receptor agonists. The serontonin 5-HT₃ receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. It is suggested that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT₃ receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: Orally-administered dolasetron is well absorbed
• Half Life: 8.1 hours
• Protein Binding: 69-77%
• Elimination: Hydrodolasetron is eliminated by multiple routes, including renal excretion and, after metabolism, mainly glucuronidation, and hydroxylation.
• Distribution: * 5.8 L/kg [adults]
• Clearance: * Apparent cl=9.4 mL/min/kg [Healthy volunteers with IV treatment dose up to 5 mg/kg]
• References: Balfour JA, Goa KL: Dolasetron. A review of its pharmacology and therapeutic potential in the management of nausea and vomiting induced by chemotherapy, radiotherapy or surgery. Drugs. 1997 Aug;54(2):273-98. [Pubmed] ; Gregory RE, Ettinger DS: 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs. 1998 Feb;55(2):173-89. [Pubmed] ; Gan TJ: Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same? CNS Drugs. 2005;19(3):225-38. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Balfour JA, Goa KL: Dolasetron. A review of its pharmacology and therapeutic potential in the management of nausea and vomiting induced by chemotherapy, radiotherapy or surgery. Drugs. 1997 Aug;54(2):273-98. Pubmed
• Gregory RE, Ettinger DS: 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs. 1998 Feb;55(2):173-89. Pubmed
• Gan TJ: Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same? CNS Drugs. 2005;19(3):225-38. Pubmed