Design, synthesis, and in vitro evaluation of 4-aminoalkyl-1(2H)-phthalazinones as potential multifunctional anti-Alzheimer’s disease agents

Design, synthesis, in vitro, and in vivo evaluation of novel phthalazinone‐based derivatives as promising acetylcholinesterase inhibitors for treatment of Alzheimer's disease

“…Moreover, the literature survey reported that phthalazinone derivatives displayed excellent inhibition against h AChE enzyme and Aβ 1–42 accumulation beside their antidepressant and antioxidant effect (Jalili‐Baleh et al 2017; Sangshetti et al, 2019; Vila et al, 2015). For example, 4‐aminoalkyl‐1(2 H )‐phthalazinone derivative II demonstrated as potent candidate for AD as it exhibited moderate h AChE inhibitory activity (IC 50 = 8.2 μM) and good activity toward self Aβ 1–42 aggregation (Ye et al, 2021). 1 H ‐pyrazolo[1,2‐ b ]phthalazine‐5,10‐dione derivatives III are another example of compounds with our desired core that showed satisfied h AChE inhibitory activity with Ki values in the range of 68.25–158.27 nM (Figure 1) (Taslimi et al, 2020).…”

Catalyst-Free Green Synthesis of Phthalazinones at Room Temperature

“…[9][10][11][12][13] Among the numerous nitrogen-containing heterocycles, phthalazinone is a kind of annulated six-membered N-heterocycles and has diverse biological activities. [14][15][16][17][18] Phthalazinone and their derivatives have been widely used in the treatment of a variety of diseases such as diabetes, hepatitis B, asthma, vascular hypertension, arrhythmia, cancers, and are as potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) (Figure 1). [19][20][21][22][23] For example, azelastine, a phthalazinone derivative, is a well-known antiallergic and antiasthmatic drug (sales $0.24 billion in 2008).…”