Oxadiazoles

Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors

“…The scaffold is a weak base and can act only as hydrogen bond acceptor. X-ray measurements of azoximes show a planar ring and suggest a double bond character for both C-N distances, which is in agreement with a lower value of 39 for the aromatic character compared to furan with a value of 43, as determined by the bird index [18,19]. The dipole moment for unsubstituted 1 (1.2 D) or substituted 2 (1.8 D) azoximes is lower compared to other oxadiazoles (Figure 4) [2,20].…”

“…2.1. 1,2,4-Oxadiazoles 1,2,4-oxadiazoles, also referred to as azoximes show diverse biological activities and are frequently employed in medicinal chemistry as hydrolysis resistant bioisosteric replacements for ester or amide functionalities [3,18]. The scaffold is a weak base and can act only as hydrogen bond acceptor.…”

“…Disubstituted azoximes are stable and can be heated in conc. sulfuric acid or recrystallized from nitric acid and show only slow decomposition at 250 • C. Mono-or unsubstituted azoximes are thermally and hydrolytically less stable [18,20]. Azoximes are rather inert against electrophilic attacks as halogenation, nitration and Friedel Crafts acylation or alkylation do not occur [20].…”

Fragmentation pathways arising from protonation at different sites in aminoalkyl‐substituted 3‐hydroxy‐1,2,5‐oxadiazoles (3‐hydroxyfurazans)

“…In an initial consideration of possible protonation sites, the known p K a values for compound 2 (3.12 and 9.28) indicated that the alkylamino side chain was protonated both in the hydrochloride salts and in protic solution. Protonation of the ring was unlikely since the parent furazan ring has p K a = −5 …”

Synthesis of Novel 3‐Aryl‐5‐dichloromethyl‐Δ2‐1,2,4‐oxadiazolines

“…The chemistry, properties, and applications of heterocyclic compounds comprising a 1,2,4-oxadiazole ring have been thoroughly reviewed [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15], showing that this nucleus confers a wide variety of biological and pharmacological activities. Regarding oxadiazolines, 4,5dihydro-1,2,4-oxadiazoles (Δ 2 -1,2,4-oxadiazolines) are distinguished as substances of significant synthetic [5,[16][17][18][19] and biological [20][21][22][23][24][25][26] interest.…”