1-methyl-N-{9-methyl-9-azabicyclo[3.3.1]nonan-3-yl}-1H-indazole-3-carboxamide

• ChemBase编号: 766
• 分子式: C18H24N4O
• 平均质量: 312.40936
• 单一同位素质量: 312.19501141
• SMILES: O=C(NC1CC2N(C(C1)CCC2)C)c1nn(c2c1cccc2)C
• Canonical SMILES: CN1C2CCCC1CC(C2)NC(=O)c1nn(c2c1cccc2)C
• InChI: InChI=1S/C18H24N4O/c1-21-13-6-5-7-14(21)11-12(10-13)19-18(23)17-15-8-3-4-9-16(15)22(2)20-17/h3-4,8-9,12-14H,5-7,10-11H2,1-2H3,(H,19,23)
• InChIKey: MFWNKCLOYSRHCJ-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 1-methyl-N-{9-methyl-9-azabicyclo[3.3.1]nonan-3-yl}-1H-indazole-3-carboxamide
• IUPAC传统名: GRAN; granisetron
• 商标名: Kytril
• 别名: exo-N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-1-methyl-1H-indazole-3-carboxamide; Granisetron Impurity F; exo-Granisetron (Granisetron Impurity F); Granisetronum [INN-Latin]; Granisetron base; Granisetron HCl; APF530; Granisetron; Granisetron hydrochloride

登记号

• CAS号: 1364914-39-5; 109889-09-0
• PubChem SID: 46505137; 160964229
• PubChem CID: 3510

理论计算性质

JChem

• Acid pKa: 14.750399
• 质子受体: 3
• 质子供体: 1
• LogD (pH = 5.5): -1.3230767
• LogD (pH = 7.4): 0.2712485
• Log P: 1.8768568
• 摩尔折射率: 101.8257 cm^3
• 极化性: 35.897053 Å^3
• 极化表面积: 50.16 Å^2
• 可自由旋转的化学键: 2
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 2.64
• LOG S: -2.86
• 溶解度: 4.34e-01 g/l

分子性质

理化性质

• 溶解度: Chloroform; Ethyl Acetate
• 外观: Off-White Solid
• 熔点: 113-115°C
• 疏水性(logP): 2.6

安全信息

• 保存条件: -20°C Freezer

详细说明

DrugBank - DB00889

• Drug Groups: approved; investigational
• Description: A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic and antinauseant for cancer chemotherapy patients. [PubChem]
• Indication: For the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy (including high dose cisplatin), postoperation, and radiation (including total body irradiation and daily fractionated abdominal radiation).
• Pharmacology: Granisetron is a selective inhibitor of type 3 serotonergic (5-HT₃) receptors. Granisetron has little or no affinity for other serotonin receptors, including 5-HT 1 , 5-HT 1A , 5-HT 1B/C , or 5-HT 2 ; for alpha 1 -, alpha 2 -, or beta-adrenoreceptors; for dopamine D 2 receptors; for histamine H 1 receptors; for benzodiazepine receptors; for picrotoxin receptors; or for opioid receptors. In most human studies, granisetron has had little effect on blood pressure, heart rate, or electrocardiogram (ECG). The drug is structurally and pharmacologically related to ondansetron, another selective inhibitor of 5-HT₃ receptors. 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. The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents suggest 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.
• Toxicity: LD₅₀>2000 mg/kg (rat, oral)
• Affected Organisms: Humans and other mammals
• Biotransformation: Primarily hepatic; undergoes N -demethylation and aromatic ring oxidation followed by conjugation. Animal studies suggest that some of the metabolites may have 5-HT 3 receptor antagonist activity.
• Absorption: Absorption of is rapid and complete, though oral bioavailability is reduced to about 60% as a result of first pass metabolism.
• Half Life: 4-6 hours in healthy patients, 9-12 hours in cancer patients
• Protein Binding: 65%
• Elimination: The remainder of the dose is excreted as metabolites, 48% in the urine and 38% in the feces.
• Clearance: * 0.52 L/h/kg [Cancer Patients with 1 mg bid for 7 days]; * 0.41 L/h/kg [Healthy subject with a single 1 mg dose]
• References: [Link] ; 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] ; Tan M: Granisetron: new insights into its use for the treatment of chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2003 Sep;4(9):1563-71. [Pubmed] ; Feyer P, Seegenschmiedt MH, Steingraeber M: Granisetron in the control of radiotherapy-induced nausea and vomiting: a comparison with other antiemetic therapies. Support Care Cancer. 2005 Sep;13(9):671-8. Epub 2005 Jul 26. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - G780010

Granisetron Impurity F.

参考文献

• Link
• 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
• Tan M: Granisetron: new insights into its use for the treatment of chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2003 Sep;4(9):1563-71. Pubmed
• Feyer P, Seegenschmiedt MH, Steingraeber M: Granisetron in the control of radiotherapy-induced nausea and vomiting: a comparison with other antiemetic therapies. Support Care Cancer. 2005 Sep;13(9):671-8. Epub 2005 Jul 26. Pubmed
• Fozard, J. R., et al.: Br. J. Pharmacol., 61, 130 (1977)
• Bradley, P.B., et al.: Neuropharmacology, 25, 563 (1977)