Three-component synthesis of pyrano[2,3-d]-pyrimidine dione derivatives facilitated by sulfonic acid nanoporous silica (SBA-Pr-SO3H) and their docking and urease inhibitory activity

Abstract

BackgroundA straightforward and efficient method for the synthesis of pyrano[2,3-d]pyrimidine diones derivatives from the reaction of barbituric acid, malononitrile and various aromatic aldehydes using SBA-Pr-SO3H as a nanocatalyst is reported.ResultsReactions proceed with high efficiency under solvent free conditions. Urease inhibitory activity of pyrano[2,3-d]pyrimidine diones derivatives were tested against Jack bean urease using phenol red method. Three compounds of 4a, 4d and 4l were not active in urease inhibition test, but compound 4a displayed slight urease activation properties. Compounds 4b, 4k, 4f, 4e, 4j, 4g and 4c with hydrophobic substitutes on phenyl ring, showed good inhibitory activity (19.45-279.14 μM).DiscussionThe compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate. Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity. Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

Recent applications of barbituric acid in multicomponent reactions

“…d] dipyrimidine-tetraones 112.According to this protocol, when (+)-D-glucose 111 and amines 73, reacted with two equivalent of barbituric acid 1 in the presence of p-toluenesulfonic acid as a catalyst, the excellent yield of products were obtained (Scheme 47) 115. This reaction was also investigated in the presence of sulfonic acid functionalized nanoporous silica SBA-Pr-SO 3 H 122. Eskandari-Vashareh have reported an efficient one-pot synthesis of a new series of spiro[benzo[h]quinoline-7,3'-indolines] 114 by the reaction of isatins 2, 1-naphthylamine 113 and barbituric acid 1 in acetic acid (Scheme 48).…”

Synthesis of chloro, fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones using organic catalysts and their antimicrobial and anticancer activities

“…With the exception of the novel, 2,4‐difluoro derivative 11 , all compounds were synthesized previously in comparable yields using a variety of methods or catalysts (Table ), including microwave synthesis without the use of a catalyst, with the ionic liquids 1‐n‐butyl‐3‐methylimidazolium tetrafluoroborate and 1‐butylpyridinium tetrafluoroborate, a Zn [(L) proline] catalyst, with glycerol without the use of a catalyst, nanocatalysts Fe 3 O 4 and SBA‐15‐Pr‐SO 3 H (a mesoporous solid acid catalyst), and ethyl cyanoacetate . DABCO has been used previously for the synthesis of furan‐2‐yl, pyrrol‐2‐yl and thiophen‐2‐yl derivatives of pyrano pyrimidin‐2,4‐diones in a one pot reaction.…”

“…Pyrimidines are generally synthesized by a Biginelli multicomponent reaction (MCR), a method considered green since they are fast, solvent free, produces good yields, and avoids exposing the environment to environmentally harmful intermediates . Pyrano[2,3‐ d ]pyrimidines are commonly formed from barbituric acid, malonitrile, and aldehdyes with a catalyst such as 1,4‐diazabicyclo[2,2,2]octane (DABCO), an organic catalyst, a mesoporous solid acid catalyst (SBA‐15‐Pr‐SO 3 H), a ZnFe 2 O 4 nanocatalyst, a nano‐sawdust‐OSO 3 H catalyst, a Mn‐doped ZrO 2 catalyst, or triethylammonium acetate (a green catalyst) . The same compounds were made using arylidenemalonitrile with barbituric acid under microwave irradiation without a catalyst or using ionic liquid catalysts such as N ‐butyl‐ N ‐methyl imidazole tetrafluoroborate [BMIm]BF 4 , N ‐ethyl‐ N ‐methyl imidazole tetrafluoroborate [EMIm]BF 4 , or N ‐butyl pyridinium tetrafluoroborate [BPy]BF 4 .…”

Application of 1‐methyl imidazole‐based ionic liquid‐stabilized silica‐coated Fe3O4 as a novel modified magnetic nanocatalyst for the synthesis of pyrano[2,3‐d]pyrimidines

“…In this sense, pyrano[2,3‐d]pyrimidines and their derivatives can be regarded as important compounds in the field of drug and pharmaceutical chemistry because of their useful characteristics such as anticoagulants, diuretics, spasmolytics, as well as anticancer and anti‐anaphylactic drugs . In recent years, many routes have been suggested for the synthesis of pyrano[2,3‐d]pyrimidines, which include base‐catalyzed (DABCO), diammonium hydrogen phosphate (DAHP), [KAl(SO 4 ) 2 ], [BMIm]BF 4 , tetrabutylammonium bromide (TBAB), triethyamine, acid‐catalyzed (SBA‐Pr‐SO 3 H, γ‐Fe 2 O 3 @HAp‐Ni 2+ , ZnO nano‐powders, Al‐HMS‐20, choline chloride.ZnCl 2 , Zn[(L)proline] 2 , ultrasonic irradiation, microwave irradiation, and catalyst‐free synthesis . However, many of these methods suffer from at least one of the following disadvantages: long reaction times, low yields of products, formation of side products, use of strong bases, use of high temperature, and use of toxic metallic catalysts.…”