A new three-component reaction: green synthesis of novel isoindolo[2,1-a]quinazoline derivatives as potent inhibitors of TNF-α

Abstract

Concurrent construction of five and six membered fused N-heretocyclic ring was achieved via a conceptually new three-component reaction affording 6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-diones as novel inhibitors of TNF-αin vitro. This represents one of the few examples of direct TNF-α inhibition by small molecules.

Delivery of drugs applied topically to the skin

“…The surfactants may be ionic, nonionic or amphoteric. Nonionic surfactants may have better skin tolerance, and only in a very few specific cases, amphoteric surfactants are used [60]. Cationic surfactants often allow improved skin penetration, as seen in the work of Klang et al [61], which concerned corneal penetration of indomethacin, and of Kitagawa and Kasamaki [62], which concerned the permeation of anionic salicylate through excised guinea pig dorsal skin.…”

Synthesis of novel fused quinazolinone derivatives

“…Some derivatives were synthesized from the reaction of oxo acids with anthranilic acid/ anthranilamides/orthanilamides, and salicylamide [19]. Furthermore, some isoindoloquinazolinediones were synthe- [17,20,21]. Focusing on the biological potential of fused quinazolinones, in continuation of our work on the synthesis of novel N -heterocycles [22][23][24][25][26][27][28], herein, we report the synthesis of novel fused quinazolinones 8 and 10 starting from isatoic anhydride 1 (Scheme 1).…”

“…Isoindoloquinazolines have shown TNF-α inhibitory [17], sedative, analgesics, and antihypertensive activities [18]. However, the synthesis of isoindoloquinazolines has been limited to a few reports.…”

Transition metal-free one-pot synthesis of nitrogen-containing heterocycles

“…R 1 = CH 3 , CH 2 CH 3 ; R 2 = Ot-Bu, NHPh; R 3 = CH 3 ; R 4 , R 5 = H, CH 3 Scheme 123 One-pot synthesis of 5H-1,4-benzodiazepine-3-carboxylates ing the catalytic efficacy of montmorillonite, Kumar et al[236] developed the synthesis of potent antinflammatory isoindolo[2,1-a]quinazoline 410 derivatives through the onepot reaction of isatoic anhydride 397, 2-formylbenzoic acid 408, and diverse substituted amines 409 under mild reaction conditions as shown in Scheme 116. reflux R = H, CH 3 ; R` = R 2 = CH 3 , C 3 H 5 , -(CH 2 ) 5 -, -(CH 2 ) 6 Scheme 124 One-pot synthesis of 1,5-benzodiazepines 39 derivatives upto 69% yields) R 2 NC R = H, 4-Cl; R 1 = Ph, CH 3 , 2-ClPh, 2F-Ph; R 2 = t-Bu, Bn, cyclohexyl, benzyl, mesityl R 3 = CH 3 , CH 2 OH,n-Pr, cyclobutyl, cyclohexyl, 4-FPh, cyclopropenyl ,R 2 ,R 3 = aliphatic, alicyclic and aromatic groups Scheme 127 Synthesis of diazepine-tetrazoles via a condensation reaction…”