Novel 6-methanesulfonamide-3,4-methylenedioxyphenyl-N-acylhydrazones: Orally effective anti-inflammatory drug candidates

Design, Synthesis, Antinociceptive and Anti-Inflammatory Activities of Novel Piroxicam Analogues

“…Thus, on irradiating at the frequency of the amide hydrogen (CON H ) in 14b , a positive NOE was observed for the signal at δ 8.71 ppm, assigned to imine hydrogen (C=N- H ), and a positive NOE was also observed for the signal at δ 2.89 ppm (C H 3 ) on irradiating imine hydrogen (N=C- H ), thus indicating the E -configuration for C=N double bond. The predominance of the E diastereoisomer of N -acylhydrazone derivatives is consistent with previous works [ 17 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ] and has been ascribed to the greater thermodynamic stability of the E in respect to the Z diastereoisomer [ 36 , 38 ].…”

“…Besides, the presence of only one peak in HPLC chromatogram and a single imine-hydrogen signal in the 1 H-NMR spectra suggest that condensation reaction was diastereoselective. Carefully comparison of amide and imine hydrogens chemical shift of compounds 14a – h with previous published NMR data for N -acylhydrazones whose stereochemistry had been established by crystallography [ 17 , 32 , 33 ] suggested the presence of the E -diastereoisomer, which was confirmed by performing a NOE experiment on compound 14b . Thus, on irradiating at the frequency of the amide hydrogen (CON H ) in 14b , a positive NOE was observed for the signal at δ 8.71 ppm, assigned to imine hydrogen (C=N- H ), and a positive NOE was also observed for the signal at δ 2.89 ppm (C H 3 ) on irradiating imine hydrogen (N=C- H ), thus indicating the E -configuration for C=N double bond.…”

“…The N -acylhydrazone (NAH; 5 ) framework has recently been recognized as a privileged structure [ 13 , 14 , 15 ] and several NAH derivatives ( Figure 2 ) have been reported with different pharmacological activities, such as PDE inhibitors 6 [ 16 ] COX inhibitors 7 [ 17 ], TRPV1 antagonists 8 [ 18 ], HIV-1 capsid protein assembly inhibitors 9 [ 19 ], and CB2 inverse agonists 10 [ 20 ], among others. Moreover, many N -acylhydrazones were described by our research group as potent anti-inflammatory and antinociceptive compounds [ 21 ], which have been attributed to the NAH framework’s ability to mimic amide group and the bis-allylic moiety of unsaturated fatty acids, such as arachidonic acid [ 22 , 23 ].…”

A "green" synthesis of N-(quinoline-3-ylmethylene)benzohydrazide derivatives and their cytotoxicity activities

“…Thus, the key intermediate 1 required for our synthesis was prepared from acetanilide according to a similar procedure reported in the literature (Scheme 1). Cyclization of acetanilide in the presence of POCl 3 and N,N-dimethyl formamide (DMF) leads to the formation of the desired intermediate 1. The other reactant, i.e., hydrazide (2), was prepared via esterification of the corresponding carboxylic acids with methanol in the presence of catalytic amount of concentrated H 2 SO 4 followed by treating the resulting ester with hydrazine hydrate in methanol.…”

“…Hydrazones and substituted hydrazones on the other hand, because of their distinctive structural features and presence of azomethine group, continue to attract the attention of the medical researchers. [3][4][5] This class of compounds show an extensive range of pharmacological properties especially antitumor activities.…”