Tailored‐design Synthesis of Sulfapyrimidine Derivatives

Abstract

In this paper, we report an efficient and convenient approach for the synthesis of tailored‐design target sulfapyrimidine derivatives expected to show remarkable antimicrobial activities. The approach is based on reacting arylsulfonyl guanidine with α,β‐unsaturated carbonyl compounds to afford N‐(4,6‐diarylpyrimidin‐2‐yl)arylsulfonamide or with ylidene derivatives to afford N‐(6‐aryl‐5‐cyanopyrimidin‐2‐yl)arylsulfonamide, N‐(4‐amino‐5‐cyano‐6‐(methylthio)‐pyrimidin‐2‐yl)‐arylsulfonamide, and N‐(5‐cyanopyrimidin‐2‐yl)arylsulfonamide compounds through Michael addition reaction. The structure of the newly synthesized compounds was confirmed from spectral data and elemental analysis.

Synthesis and crystal structure of N-(5-acetyl-4-methylpyrimidin-2-yl)benzenesulfonamide

“…Thus, many widely marketed drugs incorporate this moiety. Several pyrimidine sulfonamides and other pyrimidine analogues that could be incorporated in new designs for bioactive molecules with medicinal applications have already been considered (Azzam, 2019;Azzam et al, 2017Mohamed-Ezzat et al, 2021, 2022Elgemeie et al, 2015aElgemeie et al, ,b, 2017. The synthesis of N-(5-acetyl-4-methylpyrimidin-2-yl)benzenesulfonamide (AMBS) was reported several decades ago (Gutsche et al, 1964).…”

Morpholin-4-ium [5-cyano-6-(4-methylphenyl)-4-(morpholin-4-yl)pyrimidin-2-yl](phenylsulfonyl)amide

“…Reaction scheme. Reagents and conditions: (i) potassium hydroxide; dioxane; reflux; 2 h, (ii) phosphorus oxychloride; reflux; 1 h, and (iii) morpholine; potassium carbonate; dioxane; reflux; 2 h. enesulfonamide, 2, with ethyl (2E)-2-cyano-3-(4-methylphenyl)prop-2-enoate, 1, in the presence of potassium hydroxide, with dioxane as a solvent (Azzam, 2019). N-[4-Chloro-5cyano-6-(4-methylphenyl)pyrimidin-2-yl]benzenesulfonamide, 4, was formed by treating compound 3 with phosphorous oxychloride.…”

Efficient Synthesis and Docking Studies of Novel Benzothiazole-Based Pyrimidinesulfonamide Scaffolds as New Antiviral Agents and Hsp90α Inhibitors

“…Based on our experience in developing new synthetic approaches for the synthesis of novel benzothiazole, pyrimidine, and sulfonamide compounds in high yield, − novel compounds with potent antiviral activities are planned to be further developed and assessed as potential antiviral drugs in this work. To achieve the target compounds in high yield, the pronounced reactivity of guanidine and its derivatives will also be utilized for the development of competent strategies for the synthesis of a novel benzothiazole pyrimidine sulfonamide ring system.…”