DEXLOXIGLUMIDE

• CAT Number: M018019
• CAS Number: 119817-90-2
• Molecular Formula: C21H30Cl2N2O5
• Molecular Weight: 461.38
• Purity: ≥95%
• Target: CCK1 antagonist
• Storage: Desiccate at -20C
• IUPAC Name: (4R)-4-[(3,4-dichlorobenzoyl)amino]-5-[3-methoxypropyl(pentyl)amino]-5-oxopentanoic acid
• InChI: InChI=1S/C21H30Cl2N2O5/c1-3-4-5-11-25(12-6-13-30-2)21(29)18(9-10-19(26)27)24-20(28)15-7-8-16(22)17(23)14-15/h7-8,14,18H,3-6,9-13H2,1-2H3,(H,24,28)(H,26,27)/t18-/m1/s1
• InChIKey: QNQZBKQEIFTHFZ-GOSISDBHSA-N
• SMILES: CCCCCN(CCCOC)C(=O)C(CCC(=O)O)NC(=O)C1=CC(=C(C=C1)Cl)Cl

Dexloxiglumide, also known as CR-2017, is a CCK1 antagonist potentially for the treatment of irritable bowel syndrome. It inhibits gastrointestinal motility and reduces gastric secretions, and despite older selective CCKA antagonists such as lorglumide and devazepide having had only limited success in trials and ultimately never making it into clinical use, dexloxiglumide is being investigated as a potential treatment for a variety of gastrointestinal problems including irritable bowel syndrome, dyspepsia, constipation and pancreatitis, and has had moderate success so far although trials are still ongoing.

Reference

1:Dexloxiglumide for the treatment of constipation predominant irritable bowel syndrome. Serra J, Caballero N.Expert Opin Pharmacother. 2016 Oct;17(14):1969-74. doi: 10.1080/14656566.2016.1229306. Epub 2016 Sep 8. Review. PMID: 27590736 2:3-[5-(3,4-Dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazol-3-yl]-2-m-tolyl-propionate (JNJ-17156516), a novel, potent, and selective cholecystokinin 1 receptor antagonist: in vitro and in vivo pharmacological comparison with dexloxiglumide. Morton MF, Barrett TD, Yan W, Freedman JM, Lagaud G, Prendergast CE, Moreno V, Pyati J, Figueroa K, Li L, Wu X, Rizzolio M, Breitenbucher JG, McClure K, Shankley NP.J Pharmacol Exp Ther. 2007 Nov;323(2):562-9. Epub 2007 Aug 7. PMID: 17684117 Free Article3:Pharmacokinetic profile of dexloxiglumide. Persiani S, D/’Amato M, Jakate A, Roy P, Wangsa J, Kapil R, Rovati LC.Clin Pharmacokinet. 2006;45(12):1177-88. Review. PMID: 17112294 4:CCK1 receptor antagonist, dexloxiglumide: effects on human isolated gallbladder. Potential clinical applications. Maselli MA, Mennuni L.Minerva Gastroenterol Dietol. 2003 Sep;49(3):211-6. PMID: 16484960 5:Effect of azole antifungals ketoconazole and fluconazole on the pharmacokinetics of dexloxiglumide. Jakate AS, Roy P, Patel A, Abramowitz W, Persiani S, Wangsa J, Kapil R.Br J Clin Pharmacol. 2005 Nov;60(5):498-507. PMID: 16236040 Free PMC Article6:The single-dose pharmacokinetics of the novel CCK1 receptor antagonist, dexloxiglumide, are not influenced by age and gender. Roy P, Wangsa J, Patel A, Nolting A, Persiani S, Abramowitz W, Kapil R.Int J Clin Pharmacol Ther. 2005 Sep;43(9):444-51. PMID: 16163898 7:Effect of CCK-1 antagonist, dexloxiglumide, in female patients with irritable bowel syndrome: a pharmacodynamic and pharmacogenomic study. Cremonini F, Camilleri M, McKinzie S, Carlson P, Camilleri CE, Burton D, Thomforde G, Urrutia R, Zinsmeister AR.Am J Gastroenterol. 2005 Mar;100(3):652-63. PMID: 15743365 8:Effect of multiple-dose dexloxiglumide on the pharmacokinetics of oral contraceptives in healthy women. Roy P, Jakate AS, Patel A, Abramowitz W, Wangsa J, Persiani S, Kapil R.J Clin Pharmacol. 2005 Mar;45(3):329-36. Erratum in: J Clin Pharmacol. 2005 May;45(5):603. PMID: 15703367 9:Absorption, distribution, metabolism and excretion of the cholecystokinin-1 antagonist dexloxiglumide in the dog. Webber C, Stokes CA, Persiani S, Makovec F, McBurney A, Kapil RP, John BA, D/’Amato M, Chasseaud LF.Eur J Drug Metab Pharmacokinet. 2004 Jan-Mar;29(1):15-23. PMID: 15151166 10:Interaction of dexloxiglumide, a cholecystokinin type-1 receptor antagonist, with human cytochromes P450. Hall M, Persiani S, Cheung YL, Matthews A, Cybulski ZR, Holding JD, Kapil R, D/’Amato M, Makovec F, Rovati LC.Biopharm Drug Dispos. 2004 May;25(4):163-76. PMID: 15108219