Synthesis and quantitative structure-activity relationships of antiallergic 2-hydroxy-N-(1H-tetrazol-5-yl)benzamides and N-(2-hydroxyphenyl)-1H-tetrazole-5-carboxamides

Abstract

The synthesis and antiallergic activity of a series of 2-hydroxy-N-1H-tetrazol-5-ylbenzamides and isomeric N-(2-hydroxyphenyl)-1H-tetrazole-5-carboxamides is described. A relationship between structure and intravenous antiallergic activity in the rat passive cutaneous anaphylaxis (PCA) test has been established using a Hansch/Free-Wilson model and used to direct studies toward potent derivatives. The contribution of physicochemical properties to activity is discussed. One member of this series, N-(3-acetyl-5-fluoro-2-hydroxyphenyl)-1H-tetrazole-5-carboxamide (3f), which was selected for further evaluation, has an ID50 value of 0.16 mg/kg po and is 130 times more potent than disodium cromoglycate (DSCG) on intravenous administration.

Synthesis of Entacapone by Pd-Catalyzed Heck Coupling Reaction

“…Initially condensation was tried with bromo derivative 2 (R = H, NO 2 ) [10,11] and 2-cyano-N,N-diethylacrylamide 3, which is prepared according to literature procedure [12] with various Pd sources and bases at 80-150 °C but the reaction did not proceed (Scheme 1) to give Heck product 4.…”

Membrane transport of organics. III. Permeation of some carboxylic acids through bipolar polymer membrane

“…1‐{2‐Hydroxy‐3‐[(1 E )‐prop‐1‐en‐1‐yl]phenyl}ethanone (43) : The isomerization reaction was carried out as described29 by starting from compound 42 (315 g, 283 mmol) and Pd(C 6 H 5 CN) 2 Cl 2 (8.57 g, 22.34 mmol) to give the title compound in nearly quantitative yield (301 g, 95 %). 1 H NMR (500 MHz, [D 6 ]DMSO): δ =1.92 (dd, J =1.5 Hz, J =6.5 Hz, 3 H), 2.64 (s, 3 H), 6.30 (m, 1 H), 6.74 (d, J =15.6 Hz, 1 H), 6.85 (t, J =8.1 Hz, 1 H), 7.60 (t, J =8.1 Hz, 2 H), 12.74 ppm (s, 1 H); MS (ESI+): m / z =176 [ M ] + .…”

Biological Portfolio of 1,5-Disubstituted Tetrazoles: A Review

“…Tetrazoles, based on the number of substituent, are divided into three categories, (i) parent tetrazoles (simplest tetrazoles), (ii) monosubstituted tetrazoles (1-or 5-substituted), and (iii) disubstituted tetrazoles (1, 5-or 2,5-disubstituted). Tetrazoles are a class of heterocycles with a wide range of applications including rocket propellants 3 and explosives 4 .The tetrazoles are representative of active pharmacophores for several therapeutic active molecules such as antiallergic 5 , antiinflammatory 6 , antibiotic 7 , anti-hypertensive 8 and anti-tubercular agents 9 .…”