کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1371569 | 981849 | 2010 | 7 صفحه PDF | دانلود رایگان |
The structure–activity relationship of a novel series of 8-biarylnaphthyridinones acting as type 4 phosphodiesterase (PDE4) inhibitors for the treatment of long-term memory loss and mild cognitive impairment is described herein. The manuscript describes a new paradigm for the development of PDE4 inhibitor targeting CNS indications. This effort led to the discovery of the clinical candidate MK-0952, an intrinsically potent inhibitor (IC50 = 0.6 nM) displaying limited whole blood activity (IC50 = 555 nM). Supporting in vivo results in two preclinical efficacy tests and one test assessing adverse effects are also reported. The comparative profiles of MK-0952 and two other Merck compounds are described to validate the proposed hypothesis.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 22, 15 November 2010, Pages 6387–6393