Novel sulfenamides as promising acetylcholinesterase inhibitors

Abstract

Several sulfenamide derivatives were designed as possible acetylcholinesterase (AChE) inhibitors. New sulfenamides were synthesized and proved to be stable under the physiological conditions used in the enzymatic assays. N‐benzyl‐2‐benzoxazolylsulfenamide (8) and N‐benzyl‐2‐benzimidazolylsulfenamide (9) revealed anti‐AChE activity with IC50 values of 0.6 and 0.8 μM, respectively, values of the same magnitude as those reported for galantamine and tacrine. The affinity for the biological site was evaluated in terms of interaction/partition toward sodium dodecyl sulfate (SDS) micelles. The inhibitory activity profiles were reasoned in terms of both partition toward a hydrophobic anionic environment and molecular geometry. The XCSN dihedral angle deviations from collinearity stood out as a major parameter linked to enzyme specificity. J. Heterocyclic Chem., (2011).

A benzoxazole sulfenamide accelerator: Synthesis, structure, property, and implication in rubber vulcanization mechanism

“…The desirable benzoxazole‐2‐sulfenamide 7 (Scheme 3) was synthesized from benzoxazole‐2‐thiol 2 and tert ‐butyl amine in high yield, by using a literature procedure for a similar compound . The 1 H NMR spectrum of 7 detected four aromatic protons in anticipated two doublet and two triplet (in CDCl 3 ), confirming its structure.…”

“…The 2‐mercaptobenzoxazole (2.5 g, 0.0165 mol) and sodium hydroxide (1.3 g, 0.0325 mol) were dissolved in 70 mL of water, and then 27 mL of an aqueous solution containing 18 mL (0.169 mol) of tert ‐butylamine was added . To this solution at room temperature, 55 mL of water containing 8.4 g (0.033 mol) of iodine and 4.6 g of potassium iodide was added drop by drop with stirring until constant brown color developed.…”

Efficient Synthesis of Sulfenamides through Mitsunobu‐type Coupling Reaction of Thiols with Amines using Dibenzyl Azodicarboxylate

“…Different ring‐sized secondary amines such as pyrrolidine, and azepane, were reacted with thiol 1 a to produce the adducts 3 e and 3 f in good yields (47% and 42%, respectively). As well as secondary amines, primary amines bearing ethyl or benzyl moieties were used to form the desired products 3 g and 3 h in excellent yields (96% and 88%, respectively). In the case of less sterically hindered amines possessing cyclopropyl, cyclopentyl or cyclohexyl groups, 3 i , 3 j , and 3 k were generated in excellent yields (88% to 96%).…”

“…Divergent secondary amines including 5, 6, or 7‐membered rings were converted to 3 o , 3 p , and 3 q in yields of 65%, 26%, and 53%, respectively. The reaction of ethyl, benzyl, cyclopropyl, cyclopentyl or cyclohexyl amines gave rise to 3 r – 3 v in excellent yields (76% to 94%). To the best of our knowledge, the S−N bond formation reaction of benzo[ d ]oxazole‐2‐thiol 1 r to obtain S‐(benzo[ d ]oxazol‐2‐yl)thiohydroxylamine derivatives has not been sufficiently explored.…”

An Apparent Binary Choice in Biochemistry: Mutual Reactivity Implies Life Chooses Thiols or Nitrogen-Sulfur Bonds, but Not Both

“…The rapid N-S(II) reactivity toward cellular thiols is the basis of the mechanism of action of many antibiotics (Turos et al, 2002;Turos, 2005;Revell et al, 2007;Prosen et al, 2011;Ramaraju et al, 2012;Shang et al, 2013), pesticides (Chiu et al, 1975;Umetsu et al, 1980;Fukuto et al, 1983;Wallace and Zerba, 1989), and prodrug candidates (Olbe et al, 2003;Hemenway, 2006;Hemenway et al, 2007;Nti-Addae, 2008;Proença et al, 2011;Huttunen et al, 2012). Similarly, the reactivity of N-S(II) compounds to other common functional groups found in the cell (other than thiols) is not detected, showing that the main reactivity of N-S(II) compounds in the cellular environment comes from -SH groups and not from others (alcohols, amines, carboxylic acids, etc.)…”