New furoxan derivatives for the treatment of ocular hypertension

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:27

Article

Blangetti, Marco¹  Rolando, Barbara¹  Chegaev, Konstantin¹  Guglielmo, Stefano¹  Lazzarato, Loretta¹  Durante, Mariaconcetta²  Masini, Emanuela²  Almirante, Nicoletta³  Bastia, Elena³  Impagnatiello, Francesco³  Fruttero, Roberta¹  Gasco, Alberto¹ 

[1] Univ Turin, Dipartimento Sci & Tecnol Farm, Via P Giuria 9, I-10125 Turin, Italy

[2] Univ Florence, Dipartimento Neurosci, Area Farm & Salute Bambino NEUROFARBA, Viale Pieraccini 6, I-50139 Florence, FI, Italy

[3] Nicox Res Inst Srl, Via Ludovico Ariosto 21, I-20091 Bresso, MI, Italy

关键词: Nitric oxide;    Furoxan;    Glaucoma;    Ocular hypertension;   

DOI  :  10.1016/j.bmcl.2016.12.041

来源: Elsevier

【 摘 要 】

A small series of water-soluble NO-donor furoxans bearing a basic center at the 4-position, having a wide lipophilic-hydrophilic balance range, and endowed with different NO-release capacities, were synthesized and characterized. Selected members were studied for their LOP-lowering activity in the transient ocular hypertensive rabbit model at 1% dose. The most effective IOP-lowering products were compounds 3 and 7, whose activity 60 min after administration was similar to that of Timolol. Notably, 7 was characterized by a long-lasting action. The LOP-lowering activity in this series of products appeared to be modulated by the lipophilic-hydrophilic balance rather than by the NO-donor capacity. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

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