Department of Drug Chemistry and Technologies, Sapienza University, Rome, Italy.
Arch Pharm (Weinheim). 2013 Jan;346(1):17-22. doi: 10.1002/ardp.201200318. Epub 2012 Oct 15.
A new scaffold of hydrazothiazoles has been designed as monoamine oxidase (MAO) inhibitors combining the hydrazine moiety of iproniazid and the thiazole nucleus of glitazones, a class of peroxisome proliferator-activated receptor (PPAR)γ agonists recently co-crystallized with human MAO-B. The resulting derivatives were synthesized and assayed to evaluate their in vitro activity against both the A and B isoforms of hMAO. All compounds were shown to be selective hMAO-B inhibitors with IC(50) values in the low micromolar/high nanomolar range. Such results suggest that the hydrazothiazole scaffold could be considered as an interesting pharmacophore for the future design of new lead compounds as coadjuvants for the treatment of neurodegenerative diseases.
一个新的酰腙噻唑支架被设计为单胺氧化酶（MAO）抑制剂，结合了异丙烟肼的肼部分和噻唑核，噻唑核是最近与人类 MAO-B 共结晶的过氧化物酶体增殖物激活受体（PPAR）γ 激动剂的一类。所得衍生物被合成并进行了体外活性评估，以评估它们对 hMAO 的 A 和 B 同工酶的抑制活性。所有化合物均显示为选择性 hMAO-B 抑制剂，其 IC（50）值在低微摩尔/高纳摩尔范围内。这些结果表明，酰腙噻唑支架可被视为设计新的先导化合物的有趣药效团，作为治疗神经退行性疾病的辅助药物。
