Literature

Abstract

A new series of catechol hydrazines was synthesized and their structure-activity relationship (SAR) was analyzed for developing an effective phosphodiesterase 4 (PDE4) inhibitor as an anti-asthmatic drug candidate. Among the (E)-Analogues tested using in vitro assays, 5CC showed a strong PDE4 inhibitory activity and a significantly improved rolipram binding profile compared with rolipram, a prototype PDE4 inhibitor. Moreover, from in-vivo asthma model, we observed that (E)-Analogue 5CC had a good efficacy against guinea-pig respiratory tract inflammation and bronchoconstriction, along with a remarkably reduced emetic side effect, compared with rolipram. Conclusively, (E)-Analogue 5CC seems to be a promising candidate for the development of anti-asthmatic PDE4 inhibitors.

DOI： 10.1016/s0960-894x(03)00405-0

Improvement of therapeutic index of phosphodiesterase type IV inhibitors as anti-Asthmatics

Bioorganic & Medicinal Chemistry Letters 2003.0

Selective Type IV Phosphodiesterase Inhibitors as Antiasthmatic Agents. The Syntheses and Biological Activities of 3-(Cyclopentyloxy)-4-methoxybenzamides and Analogs

Journal of Medicinal Chemistry 1994.0

Synthesis and biological evaluation of 2,5-dihydropyrazolo[4,3-c]quinolin-3-ones, a novel series of PDE 4 inhibitors with low emetic potential and antiasthmatic properties

Bioorganic & Medicinal Chemistry Letters 2000.0

Design, synthesis and in vitro PDE4 inhibition activity of certain quinazolinone derivatives for treatment of asthma

Medicinal Chemistry Research 2012.0

Synthesis and in vitro profile of a novel series of catechol benzimidazoles. The discovery of potent, selective phosphodiesterase type IV inhibitors with greatly attenuated affinity for the [3H]rolipram binding site

Bioorganic & Medicinal Chemistry Letters 1995.0

Phthalazine PDE4 inhibitors. Part 3: The synthesis and in vitro evaluation of derivatives with a hydrogen bond acceptor