| Literature DB >> 24373735 |
Mariangela Biava1, Claudio Battilocchio2, Giovanna Poce2, Salvatore Alfonso2, Sara Consalvi2, Angela Di Capua3, Vincenzo Calderone4, Alma Martelli4, Lara Testai4, Lidia Sautebin5, Antonietta Rossi5, Carla Ghelardini6, Lorenzo Di Cesare Mannelli6, Antonio Giordani7, Stefano Persiani7, Milena Colovic7, Melania Dovizio8, Paola Patrignani8, Maurizio Anzini3.
Abstract
We report herein the development, synthesis, physicochemical and pharmacological characterization of a novel class of pharmacodynamic hybrids that selectively inhibit cyclooxygenase-2 (COX-2) isoform and present suitable nitric oxide releasing properties. The replacement of the ester moiety with the amide group gave access to in vivo more stable and active derivatives that highlighted outstanding pharmacological properties. In particular, the glycine derivative proved to be extremely active in suppressing hyperalgesia and edema.Entities:
Keywords: (t)NSAIDs; 1,5-Diarylpyrroles; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; 1-hydroxybenzotriazole; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; AA; Boc; CBz; CINODs; COX-2; CV; Coxibs; Cyclooxygenases; DMAP; DMEM; Dulbecco’s modified eagle’s medium; E(max); EDCI; FBS; GI; HOBt; HWB; LPS; NO; NO releasing moiety (nitroxy)butanol; NOBA; NSAIDs; Nitric oxide; OA; ODQ; PBS; PGE(2); Pharmacodynamic hybrids; PyBOP; RA; RIA; SAR; SGF; TX; arachidonic acid; benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate; cNOS; carboxybenzyl; cardiovascular; constitutive nitric oxide synthases; coxibs; cyclooxygenase 2; cyclooxygenase-2 inhibitors; cyclooxygenase-inhibiting nitric oxide donor; dimethylaminopyridine; fetal bovine serum; gastrointestinal; human whole blood; intraperitoneal; intraplantar; ip; ipl; lipopolysaccharide; maximal vasorelaxing response; nitric oxide; nonsteroidal anti-inflammatory drug; osteoarthritis; phosphate buffer solution; prostaglandin E(2); radioimmunoassay; rheumatoid arthritis; simulated gastric fluid; structure relationship studies; tert-butyloxycarbonyl; thromboxane; traditional nonsteroidal anti-inflammatory drug
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Year: 2013 PMID： 24373735 DOI： 10.1016/j.bmc.2013.12.008
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641