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

• ChemBase ID: 950
• Molecular Formular: C16H23N5O
• Molecular Mass: 301.38672
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: (E)-1-({[(3Z)-5-(hydroxymethyl)-3H-indol-3-ylidene]methyl}amino)-2-pentylguanidine
• IUPAC Traditional name: zelnorm
• Brand Name: Zelmac; Zelnorm
• Synonyms: SDZ HTF 919; Tegaserod maleate; tegaserod; Tegaserod

Database IDs

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

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.905367
• H Acceptors: 6
• H Donor: 4
• LogD (pH = 5.5): -0.96263856
• LogD (pH = 7.4): -0.500157
• Log P: 1.6087857
• Molar Refractivity: 112.1576 cm^3
• Polarizability: 33.29597 Å^3
• Polar Surface Area: 95.03 Å^2
• Rotatable Bonds: 7
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.03
• LOG S: -3.3
• Solubility (Water): 1.50e-01 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): 2.6

DETAILS

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• Drug Groups: withdrawn; investigational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