Phenylimino-2 H -chromen-3-carboxamide derivatives as novel small molecule inhibitors of β-secretase (BACE1)

N‐(2‐(Piperazin‐1‐yl)phenyl)arylamide Derivatives as β‐Secretase (BACE1) Inhibitors: Simple Synthesis by Ugi Four‐Component Reaction and Biological Evaluation

“…We initially designed our exploratory library in such way as to incorporate 1‐(4‐bromophenyl)‐4‐phenylpiperazine substructure as part of the amine, utilizing the U‐4CC reaction . The amine 4,5‐bromo‐2‐(4‐phenylpiperazine‐1‐yl)aniline was synthesized in two steps as illustrated in Scheme . At the first, commercially available 1,4‐dibromo‐2‐nitrobenzene ( 1 ) was reacted with 1‐phenylpiperazine ( 2 ) in the presence of triethylamine as a catalyst in refluxing 2‐propanol to afford nitro compound 3 (yield 80%).…”

“…At the first, commercially available 1,4‐dibromo‐2‐nitrobenzene ( 1 ) was reacted with 1‐phenylpiperazine ( 2 ) in the presence of triethylamine as a catalyst in refluxing 2‐propanol to afford nitro compound 3 (yield 80%). The intermediate 3 was further reduced into the amine derivative 4 by the treatment with sodium carbonate and sodium dithionate in aqueous solution at 70°C (yield 95%) . As depicted in Scheme , the novel compounds 7 – 5 were synthesized by the U‐4CC reaction of equimolar amounts of amine 4 , aromatic aldehydes 5a – f , appropriate carboxylic acids 6a – f and cyclohexyl isocyanide in methanol at 50°C.…”

“…We have previously reported novel N ‐(4‐bromophenyl)piperazine derivatives II (Fig. ) containing phenyliminochromene carboxamide scaffold as potent small molecule inhibitors of BACE1 enzyme . Some of these derivatives demonstrated good inhibitory activity on Aβ production in N2a‐APPswe cells at 5 and 10 µM.…”

An efficient three-component synthesis of coumarin-3-carbamides by use of Ni–NiO nanoparticles as magnetically separable catalyst

“…2 They are also known to act as monoamine oxidase inhibitors, 3 β-secretase (BACE1) inhibitors 4 and anti-Helicobactor pylori agents. 1 A good number of coumarin-3-(N-aryl)carbamides are known to arrest breast cancer cell growth by inhibiting ErbB-2 and ERK1.…”

1-Cyanoacetyl-3,5-dimethylpyrazole

“…Thus, imino-2H-chromen-3-carboxamide derivatives 4, inhibitors of β-secretase, were obtained in three steps starting from substituted anilines and pyrazole 1. 5 The reaction of spirocyclic amine 5 with a two-fold excess of 1 led to N-cyanoacetyl derivative 6, an inhibitor of Janus kinase 3. 6,7 (B) Synthesis of Oxadiazoles New 5-cyanomethyl-1,2,4-oxadiazoles 7 have been synthesized by the reaction of pyrazole 1 with arylamidoximes.…”