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

• ChemBase编号: 637
• 分子式: C19H20N2O3
• 平均质量: 324.3737
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: (3R)-10-oxo-8-azatricyclo[5.3.1.0^{3,8}]undecan-5-yl 1H-indole-3-carboxylate
• IUPAC传统名: dolasetron
• 商标名: Anzemet; Dolasetronum [INN-Latin]; Dolasteron
• 别名: Dolasetron

登记号

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

理论计算性质

JChem

• Acid pKa: 12.182263
• 质子受体: 3
• 质子供体: 1
• LogD (pH = 5.5): 1.923664
• LogD (pH = 7.4): 2.3176217
• Log P: 2.3258903
• 摩尔折射率: 89.3352 cm^3
• 极化性: 35.947193 Å^3
• 极化表面积: 62.4 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 2.41
• LOG S: -3.09
• 溶解度: 2.61e-01 g/l

分子性质

理化性质

• 溶解度: Freely soluble in water
• 疏水性(logP): 2.1

详细说明

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

参考文献

• 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