title: Enhanced water-soluble derivative of PC407 as a novel potential COX-2 inhibitor injectable formulation.
abstract: PC407 is an effective COX-2 inhibitor in non-steroidal anti-inflammatory drug development but the poor solubility limits their usefulness. The aim of the study was to prepare and evaluate 4-oxo-4-[4-(5-(naphthalen-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamido]butyrate disodium, a derivative of PC407 with enhanced water solubility for injectable formulation. The prepared derivative displayed interesting high aqueous solubility (20.3 mg/mL, much superior to the parent compound PC407, 1.6 μg/mL) with confirmed in vivo analgesic activity. This derivative represents the profiles of prodrug and potential candidate of PC407 for the development of injectable COX-2 inhibitor due to extraordinary water solubility, low toxicity, and impressive analgesic activity.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
authors.forename: Meng-Lei
authors.initials: ML
authors.lastname: Huan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
authors.forename: Yi-Yang
authors.initials: YY
authors.lastname: Jia
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yuan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China. Electronic address: blezhang@fmmu.edu.cn.
authors.forename: Bang-Le
authors.initials: BL
authors.lastname: Zhang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D015394:Molecular Structure; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D014867:Water / Q000737:chemistry
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; C000596290:PC407 compound; D011355:Prodrugs; D011720:Pyrazoles; D013449:Sulfonamides; D014867:Water; D051546:Cyclooxygenase 2
keywords: COX-2 inhibitor; Injectable formulation; Prodrug; Solubility