Synthesis and quantitative structure–activity relationship study of substituted imidazophosphor ester based tetrazolo[1,5-b]pyridazines as antinociceptive/anti-inflammatory agents

Abstract

SummaryA high-yielding general synthesis of imidazophosphor ester based tetrazolo[1,5-b]pyridazines is described. A conjugated reaction between 3,6-diazidopyridazine and different types of phosphonyl carbanion reagents followed by intramolecular cyclization afforded the target products, by using sodium ethanolate solution as a reaction medium. Among the products, five compounds, at a dose of 50 mg per kilogram body weight, showed a notable antinociceptive and anti-inflammatory activity without toxic side-effects.

Progress in intermolecular and intramolecular reactions of thioamides with diazo compounds and azides

“…Dihydroimidazole. A unique reaction, where the reacting center in the thioamide counterpart is neither C@S nor C-NH 2 bond but a central C atom, is the cyclization of 3,6-diazidopyridazine 71 with diethyl (2-amino-2-thioxoethyl)phosphonate (72) in the presence of EtONa (Scheme 21) [61]. The authors postulate the intermediacy of the tetrazolopyrazine 73 resulting from the attack of the nitrene that could be formed from the azide 71, onto the CH 2 in phosphonate 72.…”

Structure–Activity Relationship of Terpenes with Anti‐Inflammatory Profile – A Systematic Review

“…Despite the existing technology in organic chemistry for the synthesis of a new drug, the natural products, including terpenes, serve as a source of raw material for innovative drug discovery , once the chemical diversity of terpenes is well suited to provide skeleton for future drugs . Thus, in an attempt to improve the efficacy/safety profile of new anti‐inflammatory drugs, including those of natural origin, the structure–activity relationship has been extensively studied, taking into account up‐to‐date knowledge on the mechanism of inflammation . Despite its importance, there are no reviews on the anti‐inflammatory activity of structurally modified terpenes.…”

Three‐Component Synthesis of Tetrazolo Anthraquinone as a Representation of a New Heterocyclic System

“…Moreover, as one of the polynitrogen electron‐rich backbone heterocycles, tetrazoles occupy an outstanding position in the arena of therapeutic and pesticidal chemistry due to a diversity of biological and pharmacological activity ,. On one hand, Tetrazoles and its derivatives contain significant antiviral, antibacterial, antimicrobial, anti‐inflammatory, and anticancer properties, among them such prominent drug molecules as antihypertensive drugs Losartan and its resemblance or the peptidase inhibitor CGS‐26303; on the other hand, they also display various pesticidal activity and are used as insecticides, fungicides, and plant growth regulators …”

“…[19] Moreover, as one of the polynitrogen electron-rich backbone heterocycles, tetrazoles [20] occupy an outstanding position in the arena of therapeutic and pesticidal chemistry due to a diversity of biological and pharmacological activity. [21,22] On one hand, Tetrazoles and its derivatives contain significant antiviral, [23] antibacterial, [24] antimicrobial, [25] antiinflammatory, [26] and anticancer [27] properties, among them such prominent drug molecules as antihypertensive drugs Losartan [21] and its resemblance or the peptidase inhibitor CGS-26303; [28] on the other hand, they also display various pesticidal activity and are used as insecticides, [29] fungicides, [30] and plant growth regulators. [31] In view of these findings of the utility unique structural feature of tetrazolo heterocyclic compounds and anthraquinones in the immense biological activities and their therapeutic effect, as a part of our own attention research for the synthesis of this classes of compounds, herein we attempted to describe an efficient and mild conditions protocol for the synthesis of novel (1H-tetrazole-1-yl) anthracene-9,10-dione via a one-pot cyclization of amino anthraquinones, triethyl orthoformate and sodium azide in the presence of a catalytic amount of p-TSA in acetic acid at room temperature as a part of a wider programme to provide amended protocols for the synthesis of new heterocyclic compounds.…”