Enhancing the pharmacodynamic profile of a class of selective COX-2 inhibiting nitric oxide donors
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- 作者：Mariangela Biava ; Claudio Battilocchio ; Giovanna Poce ; Salvatore Alfonso ; Sara Consalvi ; Angela Di Capua ; Vincenzo Calderone ; Alma Martelli ; Lara Testai ; Lidia Sautebin ; Antonietta Rossi ; Carla Ghelardini ; Lorenzo Di Cesare Mannelli ; Antonio Giordani ; Stefano Persiani ; Milena Colovic ; Melania Dovizio ; Paola Patrignani ; Maurizio Anzini
- 关键词：NSAIDs ; nonsteroidal anti-inflammatory drug ; (t)NSAIDs ; traditional nonsteroidal anti-inflammatory drug ; GI ; gastrointestinal ; CV ; cardiovascular ; COX-2 ; cyclooxygenase 2 ; RA ; rheumatoid arthritis ; OA ; osteoarthritis ; coxibs ; cyclooxygenase-2 inhibitors ; NO ; nitric oxide ; CINODs ; cyclooxygenase-inhibiting nitric oxide donor ; NOBA ; NO releasing moiety (nitroxy)butanol ; cNOS ; constitutive nitric oxide synthases ; SAR ; structure relationship studies ; EDCI ; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimi
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：15 January, 2014
- 年：2014
- 卷：22
- 期：2
- 页码：772-786
- 全文大小：1477 K
文摘
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.