Synthesis of New Visnagen and Khellin Furochromone Pyrimidine Derivatives and Their Anti-Inflammatory and Analgesic Activity

Abstract

6-[(4-Methoxy/4,9-dimethoxy)-7-methylfurochromen-5-ylideneamino]-2-thioxo-2,3-dihydropyrimidin-4-ones 1a,b were prepared by reaction of 6-amino-2-thiouracil with visnagen or khellin, respectively. Reaction of 1a,b with methyl iodide afforded furochromenylideneaminomethylsulfanylpyrimidin-4-ones 2a,b. Compounds 2a,b were reacted with secondary aliphatic amines to give the corresponding furochromen-ylideneamino-2-substituted pyrimidin-4-ones 3a-d. Reaction of 3a-d with phosphorus oxychloride yielded 6-chlorofurochromenylidenepyrimidinamines 4a-d, which were reacted with secondary amines to afford furochromenylideneamino-2,6-disubstituted pyrimidin-4-ones 5a-d. In addition, reaction of 5a-d with 3-chloropentane-2,4-dione gave 3-chloro-furochromenylpyrimidopyrimidines 6a-d. The latter were reacted with piperazine and morpholine to give 1-(furochromenyl)-pyrimidopyrimidine-3,6,8-triylpiperazines or-3,6,8-triylmorpholines 7a-d. The chemical structures of the newly synthesized compound ware characterized by IR, 1H-NMR, 13C-NMR and mass spectral analysis. These compounds were also screened for their analgesic and anti-inflammatory activities. Some of them, particularly 3-7, exhibited promising activities.

Design, Synthesis of Novel Thiourea and Pyrimidine Derivatives as Potential Antitumor Agents

“…Condensation of (11b) with acetylacetone, ethylacetoacetate and malononitrile in Zn/AcOH afforded the tetrahydropyrimidinethione derivatives (12)(13)(14), whereas the bis-acetyl derivative (15) was achieved when acetic anhydride was used (Scheme 2), according to the plausible mechanism in (Scheme 3). The 1 H NMR spectrums of (14) exhibited two triplet signals at d 1.20, 4.13 ppm for four protons in pyrimidine ring, a singlet signal 4.70 ppm for four protons of (CH 2 Moreover, the reaction of (11b) with chloroacetyl chloride in ethanol and in the presence of potassium hydroxide gave the corresponding 5-chloro-3-(4-chlorobenzyl)-6-(4-chloro-phenyl)-2-thioxo-tetrahydro-pyrimidi n-4-one (16).…”

Khellin and Visnagin Differentially Modulate AHR Signaling and Downstream CYP1A Activity in Human Liver Cells

“…Khellin has been extensively used by the pharmaceutical industry as basic raw material for the development of drugs such as the anti-asthmatic agent sodium cromoglycate or the widely used anti-arrhythmic drug amiodarone [18]. Recent studies identified derivatives of khellin and visnagin as suitable agents to treat different types of tumors, epileptic seizures, kidney stones and inflammatory diseases [19–22]. Due to its photosensitizing properties and lesser phototoxic side-effects compared to psoralens, khellin is also used in the photochemotherapy (khellin treatment plus ultraviolet A irradiation; KUVA) of vitiligo, a pigmentation disorder of the skin [23,24].…”

Effect of Methyl-Β-Cyclodextrin Complexation on the Hypoglycemic and Hypolipidemic Effects of Khellin: Experimental Study

“…It is mainly used as a remedy for kidney stones by slowing the buildup of calcium oxalate and by acting as a diuretic [23,24]. Advanced studies identified derivatives of KH to treat different types of tumors, epileptic seizures and inflammatory diseases [25][26][27]. Moreover, a previous study performed on the aqueous extract of Ammi Visnaga proved its significant antidiabetic effect in both normal and diabetic rats [28].…”