velusetrag   Click here for help

GtoPdb Ligand ID: 8425

Synonyms: compound 15 [PMID 22959244] | TD-5108
Compound class: Synthetic organic
Comment: Velusetrag is a potent and selective, orally available agonist of the 5-HT4 receptor. The compound is being investigated as a treatment for chronic constipation [6,8] and irritable bowel syndrome [7].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 120.33
Molecular weight 504.24
XLogP 2.68
No. Lipinski's rules broken 0
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Canonical SMILES OC(CN(S(=O)(=O)C)C)CN1C2CCC1CC(C2)NC(=O)c1cc2ccccc2n(c1=O)C(C)C
Isomeric SMILES O[C@@H](CN(S(=O)(=O)C)C)CN1[C@@H]2CC[C@H]1CC(C2)NC(=O)c1cc2ccccc2n(c1=O)C(C)C
InChI InChI=1S/C25H36N4O5S/c1-16(2)29-23-8-6-5-7-17(23)11-22(25(29)32)24(31)26-18-12-19-9-10-20(13-18)28(19)15-21(30)14-27(3)35(4,33)34/h5-8,11,16,18-21,30H,9-10,12-15H2,1-4H3,(H,26,31)/t18?,19-,20+,21-/m0/s1
1. Baker DE. (2005)
Rationale for using serotonergic agents to treat irritable bowel syndrome.
Am J Health Syst Pharm, 62 (7): 700-11; quiz 712-3. [PMID:15790796]
2. Gershon MD, Tack J. (2007)
The serotonin signaling system: from basic understanding to drug development for functional GI disorders.
Gastroenterology, 132 (1): 397-414. [PMID:17241888]
3. Hansen MB, Skadhauge E. (1997)
Signal transduction pathways for serotonin as an intestinal secretagogue.
Comp Biochem Physiol A Physiol, 118 (2): 283-90. [PMID:9366057]
4. Kadowaki M, Wade PR, Gershon MD. (1996)
Participation of 5-HT3, 5-HT4, and nicotinic receptors in the peristaltic reflex of guinea pig distal colon.
Am J Physiol, 271 (5 Pt 1): G849-57. [PMID:8944700]
5. Kim DY, Camilleri M. (2000)
Serotonin: a mediator of the brain-gut connection.
Am J Gastroenterol, 95 (10): 2698-709. [PMID:11051338]
6. Long DD, Armstrong SR, Beattie DT, Choi SK, Fatheree PR, Gendron RA, Genov D, Goldblum AA, Humphrey PP, Jiang L et al.. (2012)
Discovery, oral pharmacokinetics and in vivo efficacy of velusetrag, a highly selective 5-HT(4) receptor agonist that has achieved proof-of-concept in patients with chronic idiopathic constipation.
Bioorg Med Chem Lett, 22 (19): 6048-52. [PMID:22959244]
7. Manabe N, Wong BS, Camilleri M. (2010)
New-generation 5-HT4 receptor agonists: potential for treatment of gastrointestinal motility disorders.
Expert Opin Investig Drugs, 19 (6): 765-75. [PMID:20408739]
8. Mozaffari S, Didari T, Nikfar S, Abdollahi M. (2014)
Phase II drugs under clinical investigation for the treatment of chronic constipation.
Expert Opin Investig Drugs, 23 (11): 1485-97. [PMID:24960333]
9. Smith JA, Beattie DT, Marquess D, Shaw JP, Vickery RG, Humphrey PP. (2008)
The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity.
Naunyn Schmiedebergs Arch Pharmacol, 378 (1): 125-37. [PMID:18415081]