Synthesis and Biological Activity of New [1,3]Thiazolo[4,5-d]pyridazin-4(5H)-ones

Anatoly Demchenko

doi:10.3797/scipharm.1505-16

Abstract

A series of novel 2-(N-pyrrolidino, N-piperidino or N-morpholino)-7-phenyl(α-furoyl or α-thienyl)-[1,3]thiazolo[4,5-d]pyridazinones 10a–c, 14–16a,b was synthesized in 78–87% yields via the reaction of methyl 5-benzoyl(α-furoyl or α-thienyl)-2-aminosubstituted-thiazol-4-carboxylates 9a–c, 13a–e with hydrazine. These new compounds have been tested for their in vivo analgesic and anti-inflammatory activities. All compounds have been characterized by 1H-NMR, 13C-NMR spectroscopy, and liquid chromatography–mass spectrometry.

Highlights

Synthesis of novel 7-Chloro-4-({[5-(6,8-dibromo-2-oxo-2H-1-benzopyran-3-yl)-1,3-thiazol2-yl]amino}methyl)quinolin-2(1H)-one as an anti-inflammatory and analgesic agent that contains a thiazole ring was described previously [1]
The anti-inflammatory and analgesic activity was shown in compounds containing the thiazole and pyridazinone fragments (Sch. 1)
Intermediate compounds 4a–c for the synthesis of new [1,3]thiazolo[4,5-d]pyridazinones were synthesized by Scheme 2

Summary

Introduction

Synthesis of novel 7-Chloro-4-({[5-(6,8-dibromo-2-oxo-2H-1-benzopyran-3-yl)-1,3-thiazol2-yl]amino}methyl)quinolin-2(1H)-one as an anti-inflammatory and analgesic agent that contains a thiazole ring was described previously [1]. Comparative evaluation of analgesic activity and antiexudative effect of derivatives [1,3]thiazolo[4,5-d]pyridazinones (10a–c, 14–16a,b) and ketorolac In applying substances 10a, 16a,b in the acetic acidinduced writhing test on the mice at the dose of 25 mg/kg, a significant analgesic effect was determined 60 min after administration (Table 1).

Results

Conclusion