(E)-1-({[(3Z)-5-(hydroxymethyl)-3H-indol-3-ylidene]methyl}amino)-2-pentylguanidine

• ChemBase编号: 950
• 分子式: C16H23N5O
• 平均质量: 301.38672
• 单一同位素质量: 301.19026038
• SMILES: OCc1cc2c(N=C/C/2=C\NN/C(=N/CCCCC)/N)cc1
• Canonical SMILES: CCCCC/N=C(/NN/C=C/1\C=Nc2c1cc(CO)cc2)\N
• InChI: InChI=1S/C16H23N5O/c1-2-3-4-7-18-16(17)21-20-10-13-9-19-15-6-5-12(11-22)8-14(13)15/h5-6,8-10,20,22H,2-4,7,11H2,1H3,(H3,17,18,21)/b13-10+
• InChIKey: URPUECXJHQGUDU-JLHYYAGUSA-N

名称和登记号

名称

• IUPAC标准名: (E)-1-({[(3Z)-5-(hydroxymethyl)-3H-indol-3-ylidene]methyl}amino)-2-pentylguanidine
• IUPAC传统名: zelnorm
• 商标名: Zelmac; Zelnorm
• 别名: SDZ HTF 919; Tegaserod maleate; tegaserod; Tegaserod

登记号

• CAS号: 189188-57-6
• PubChem SID: 46506519; 160964413
• PubChem CID: 5487301

理论计算性质

JChem

• Acid pKa: 14.905367
• 质子受体: 6
• 质子供体: 4
• LogD (pH = 5.5): -0.96263856
• LogD (pH = 7.4): -0.500157
• Log P: 1.6087857
• 摩尔折射率: 112.1576 cm^3
• 极化性: 33.29597 Å^3
• 极化表面积: 95.03 Å^2
• 可自由旋转的化学键: 7
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 1.03
• LOG S: -3.3
• 溶解度: 1.50e-01 g/l

分子性质

理化性质

• 疏水性(logP): 2.6

详细说明

DrugBank - DB01079

• Drug Groups: withdrawn; investigational
• Description: Tegaserod is a 5-HT4 agonist manufactured by Novartis and used for the management of irritable bowel syndrome and constipation. Its use was the only drug approved by the United States Food and Drug Administration to help relieve the abdominal discomfort, bloating and constipation associated with irritable bowel syndrome. On March 30, 2007, the U.S. Food and Drug Administration requested that Novartis withdraw Zelnorm from shelves. The FDA alleges a relationship between prescriptions of the drug and increased risks of heart attack or stroke. [Wikipedia]
• Indication: Provides relief from the symptoms of irritable bowel syndrome including chronic idiopathic constipation.
• Pharmacology: Tegaserod is indicated for the short-term treatment of women with irritable bowel syndrome (IBS) whose primary bowel symptom is constipation. Irritable bowel syndrome with constipation and chronic idiopathic constipation are both lower gastrointestinal dysmotility disorders. Clinical investigations have shown that both motor and sensory functions of the gut appear to be altered in patients suffering from irritable bowel syndrome (IBS), while in patients with chronic idiopathic constipation, reduced intestinal motility is the predominant cause of the condition. Both the enteric nervous system, which acts to integrate and process information in the gut, and 5-hydroxytryptamine (5-HT, serotonin) are thought to represent key elements in the etiology of both IBS and idiopathic constipation. Approximately 95% of serotonin is found throughout the gastrointestinal tract, primarily stored in enterochromaffin cells but also in enteric nerves acting as a neurotransmitter. Serotonin has been shown to be involved in regulating motility, visceral sensitivity and intestinal secretion. Investigations suggest an important role of serotonin Type-4 (5-HT₄) receptors in the maintenance of gastrointestinal functions in humans. 5-HT₄ receptor mRNA has been found throughout the human gastrointestinal tract.
• Toxicity: Oral LD₅₀ in rat is 2000 mg/kg.
• Affected Organisms: Humans and other mammals
• Biotransformation: Tegaserod is metabolized mainly via two pathways. The first is a presystemic acid catalyzed hydrolysis in the stomach followed by oxidation and conjugation which produces the main metabolite of tegaserod, 5-methoxyindole-3-carboxylic acid glucuronide. The main metabolite has negligible affinity for 5-HT₄ receptors in vitro. The second metabolic pathway of tegaserod is direct glucuronidation which leads to generation of three isomeric N-glucuronides.
• Absorption: Rapidly absorbed after oral administration, with an absolute bioavailability of approximately 10%.
• Half Life: 11 ± 5 hours
• Protein Binding: 98%
• Elimination: Approximately two-thirds of the orally administered dose of tegaserod is excreted unchanged in the feces, with the remaining one-third excreted in the urine, primarily as the main metabolite.
• Distribution: * 368 ± 223 L
• Clearance: * 77 +/- 15 L/h [IV administration]
• External Links: Wikipedia; RxList; Drugs.com