Synthesis, characterization, and PK/PD studies of a series of spirocyclic pyranochromene BACE1 inhibitors

Synthesis of some novel pyrano[2,3-f]chromenone derivatives

“…The formation of compound 10 has been depicted in Scheme 3. It is presumed that heating 9 led to [3]-sigmatropic rearrangement and intermediates 12 and 13 were formed. Finally, [1,5-H] shift gave 14 following with cyclization to obtain the related compound 10.…”

“…At this juncture, promising biological properties such as antitubercular [2], BACE1 inhibitory [3], anticancer (in human leukemia) [4], and antimicrobial activities [5] of pyranochromenes have attracted medicinal chemists attention. Also, they are widely present in naturally occurring compounds such as deguelin (a), glyinflanin K (b), and glyasperin M (c) (Fig.…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…467) for total synthesis of aspeverin [896]: (3) transformation of the polyether aldehyde 468 to the corresponding alkene 469 through Tebbe olefination for synthesis of a simplified maitotoxin [897]; (4) methylenation of aryl acetates using the Tebbe reagent for the preparation of benzofurans [898]; (5) methylenation of benzopyranones using the Tebbe reagent for the preparation BACE1 inhibitors [899]; and (6) one-pot conversion of succinic anhydrides (e.g. 470) to 2,5-dimethylpyrroles (e.g.…”

Development and Structural Modification of BACE1 Inhibitors

“…Malamas et al designed 22 ( Figure 6 ), a type of BACE1 inhibitor with a pyrazolyl ring and a pyrimidine as well, which enhanced the selectivity against BACE2 and cathepsin D [ 45 ]. Moreover, Volgraf and Chen made the phenyl ring and the Ar 2 connect with an oxygen atom respectively, and this could also increase the inhibitory effect (compound 23 with an IC 50 value of 110 nM and compound 24 with an IC 50 value 0.9 nM) [ 43 , 46 ]. Besides, different structure modifications were made in pentatomic rings (compounds 25 , 26 , 27 , Figure 6 ), and these compounds all showed good BACE1 inhibitory activities as their IC 50 values ranged from 0.05 μM to 5.96 μM [ 47 , 48 ].…”