126210-90-0Relevant articles and documents
Synthesis, biological evaluation, and molecular modeling of nitrile-containing compounds: Exploring multiple activities as anti-Alzheimer agents
Silva, Daniel,Mendes, Eduarda,Summers, Eleanor J.,Neca, Ana,Jacinto, Ana C.,Reis, Telma,Agostinho, Paula,Bolea, Irene,Jimeno, M. Luisa,Mateus, M. Luisa,Oliveira-Campos, Ana M. F.,Unzeta, Mercedes,Marco-Contelles, José,Majekova, Magdalena,Ramsay, Rona R.,Carreiras, M. Carmo
, p. 215 - 231 (2019/09/03)
Based on the monoamine oxidase (MAO) inhibition properties of aminoheterocycles with a carbonitrile group we have carried out a systematic exploration to discover new classes of carbonitriles endowed with dual MAO and AChE inhibitory activities, and Aβ anti-aggregating properties. Eighty-three nitrile-containing compounds, 13 of which are new, were synthesized and evaluated. in vitro screening revealed that 31, a new compound, presented the best lead for trifunctional inhibition against MAO A (0.34 μM), MAO B (0.26 μM), and AChE (52 μM), while 32 exhibited a lead for selective MAO A (0.12 μM) inhibition coupled to AChE (48 μM) inhibition. Computational analysis revealed that the malononitrile group can find an advantageous position with the aromatic cleft and FAD of MAO A or MAO B. However, the total binding energy can be handicapped by an internal penalty caused by twisting of the ligand molecule and subsequent disruption of the conjugation (32 in MAO B compared to the conjugated 31). Conjugation is also important for AChE as well as the hydrophilic character of malononitrile that allows this group to be in close contact with the aqueous environment as seen for 83. Although the effect of 31 and 32 against Aβ1–42, was very weak, the effect of 63 and 65, and of the new compound 75, indicated that these compounds were able to disaggregate Aβ1–42 fibrils. The most effective was 63, a (phenylhydrazinylidene)propanedinitrile derivative that also inhibited MAO A (1.65 μM), making it a potential lead for Alzheimer's disease application.
Reaction of Aminopropanedinitrile 4-Methylbenzenesulfonate with Aromatic Aldehydes
Freeman, Fillmore,Kim, Darrick S. H. L.
, p. 657 - 663 (2007/10/02)
Aminpropanedinitril 4-methylbenzenesulfonate (ammoniopropanedinitrile p-toluenesulfonate, aminomalonitrile p-toluenesulfonate (tosylate), 1) reacts with aromatic aldehydes in methanolic sodium ethanoate to give diastereoselctively (E,E)-4-amino-1-aryl-3-cyano-4-methoxy-2-aza-1,3-butadienes (3) and trans-3,6-diaryl-2,2,5,5-tetracyanopiperazines (4).The product distribution (3:4) depends on the ratio of reactants and the structures of the substrates.Electron-releasing groups on the 4-position of the phenyl ring favor piperazine (4) formation (method B).The formation of piperazine (4) may involve synthetically useful N-protonated aryl- and cyano-stabilized azomethine ylide tautomerism of prior formed 1-aryl-3,3-dicyano-2-aza-1-propenes. 1,3-Dipolar cycloaddition reactions of the highly reactive azomethine ylides with dimethyl 1,2-ethynedicarboxylate (DMAD) give 3,4-dicarbomethoxy-2-cyano-5-aryl-3-pyrrolines, which undergo facile dehydrocyanation to 3,4-dicarbomethoxy-2-cyano-5-arylpyrroles.The possible intermediacy of ketenimines and of aryl- and cyano-stabilized 2-azaallyl anionic intermediates in equilibrium with azomethine ylides is also considered.
Preparation of (E,E)-4-Amino-1-aryl-3-cyano-4-methoxy-2-azabutadienes
Freeman, Fillmore,Kim, Darrick S. H. L.
, p. 698 - 699 (2007/10/02)
Aromatic aldehydes react with ammoniopropanedinitrile p-toluenesulfonate (ammoniomalononitrile tosylate, AMNT) to give (E,E)-4-amino-1-aryl-3-cyano-4-methoxy-2-azabutadienes.
