Enhancing the pharmacodynamic profile of a class of selective COX-2 inhibiting nitric oxide donors.
Bioorg Med Chem
; 22(2): 772-86, 2014 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-24373735
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.
Palabras clave
(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
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ciclooxigenasa 2
/
Inhibidores de la Ciclooxigenasa 2
/
Amidas
/
Glicina
/
Óxido Nítrico
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2014
Tipo del documento:
Article