Synthesis and biological evaluation of thieno[2,3-d]pyrimidine derivatives for anti-inflammatory, analgesic and ulcerogenic activity

Abstract

Pyrimidine and thienopyrimidine derivatives have attracted a great deal of interest owing to their medicinal activities (1-4). Pyrimidine derivatives and heterocyclic annelated pyrimidines continue to attract great interest due to the wide variety of interesting biological activities observed for these compounds, such as anticancer (4), antiviral (5), antitumor (6), anti-inflammatory (7) and antimicrobial activities (8). Also, the rapid growth in the literature dealing with the synthesis and biological activity of the thienopyrimidine derivatives prompted us to synthesize new derivatives of fused pyrimidine, thienopyrimidine and thienopyridine derivatives. In our previous work (9, 10), we reported the behaviour of thienopyrimidine derivatives towards hydrazines, 1,3-diketones, a-haloketones and acids. As part of this work, here we report a new synthesis strategy for the preparation of functionalized thieno [2,3-d] 5-Methyl-6-phenyl-2-thioxothieno[2,3-d]pyrimidone derivative (2) reacted with hydrazonoyl chloride derivatives to afford triazolothienopyrimidones 4a-f. Also, acetone--1-(2-amino-5-isopropyl-thiophene-3-carbonitrile) (3) reacted with functional and bifunctional groups to yield the corresponding compounds 5-11. The new products showed anti-inflammatory, analgesic, and ulcerogenic activities comparable to that of indomethacin and acetylsalicylic acid, respectively.

Facile heterocyclic synthesis and antimicrobial activity of polysubstituted and condensed pyrazolopyranopyrimidine and pyrazolopyranotriazine derivatives

“…The solid was recrystallized from the appropriate solvent. [4',3':5,6]pyrano [3,2-e] [1,2,4]triazolo- [1,5-c]pyrimidine-2(3H)-thione (13). -To a solution of 2 (0.31 g, 10 mmol in dry pyridine (30 ml), CS 2 (20 mmol) was added and the reaction mixture was heated under reflux for 8 h. After cooling, the reaction mixture was poured onto ice/HCl mixture and the solid that separated was washed with cold water and filtered off to give 13 as yellow powder.…”

“…All microorganisms were purchased from the American Type Culture Collection (manassas, uSA). The newly synthesized compounds (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were dissolved in dmSO and tested for antimicrobial activity with the agar disk diffusion technique (21), using a 1-cm microplate-well diameter and a solution of 100 mg ml -1 of the test compound. Compound-impregnated disks were placed on an agar plate containing a standard suspension of microorganisms.…”

“…Also, pyrane derivatives are well known antihistaminic agents (11). moreover, it has been noticed that introduction of an additional ring to the pyrimidine core tends to exert a profound influence in conferring novel biological activities in these molecules (12)(13)(14). Pyrimidine and their fused derivatives play an essential role in several biological processes and have considerable chemical and pharmacological importance.…”

Synthesis and Antibacterial Activity of Thienopyrimidine Amide Derivatives

“…This scaffold shows a broad spectrum of biological activities. The thienopyrimidines were assessed as antitumour [6][7][8][9], medicine [10], enzyme [11][12][13][14], phosphodiesterase inhibitors [15], antioxidative [16,17], antimalarial drug [18,19], antibacterial drug [20], antiviral [21], antifungal [22,23], medication [24], antiplatelet [25] and medicament [26]. In view of these observations, the varied biological property of thienopyrimidine pharmacophore impelled to synthesize the title compounds.…”

Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities

“…Thienopyrimidines make an important class of heterocyclic compounds, which have attracted a great deal of attention due to their wide range of chemotherapeutic activities, including antimicrobial (1)(2)(3)(4), moderate activity against tumor cell proliferation in vitro (5)(6)(7), antiviral (8,9), analgesic and anti-inflammatory (10)(11)(12)(13), antihistaminic (14) and anticonvulsant activities (15). With a variety of derivatives obtained by annulations and functional group manipulations, many thieno[3,2-d]-pyrimidine derivatives occupy a special place because of their biological activities such as kinase (16)(17)(18) and phosphodiesterase IV inhibiting (19,20), gastric antisecretory (21) and antifolating (22) ones.…”