Nitrodihydropyrimidines (review)

Abstract

Published data on the production and chemical transformations of nitrodihydropyrimidines are reviewed. Examples of substances having high biological activity are given.The pyrimidine fragment is present in the molecules of a series of biologically active compounds, many of which have found use in medical practice (soporific, antiinflammatory, antitumor, and other products) [1, 2]. In this connection, great attention has recently been paid to derivatives of pyrimidine, including their hydrogenation products. The first investigations into the synthesis of such compo~ctS" appeared more than a hundred years ago (e.g., the Biginelli reaction [3]), and for a long time they remained unused. Only in the last decade have methods been developed specifically for the production of hydrogenated pyrimidine system~ and their physicochemical properties been studied. This is explained by the high reactivity and by the wide range of biological activity in these derivatives. Thus, for example, 2-substituted 5-alkoxycarbonyl-4-aryl-l,4dihydropyrimidines, which are structural analogs of Hantsch esters, are modulators of the transport of calcium through membranes [4][5][6][7]. Recently, non-nucleosidic inhibitors of reverse transcriptase, which have high activity against HIV-1, have been found among hydrogenated quinazolines [8][9][10]. Many hydrogenated pyrimidines exhibit antimicrobial [11], hypoglemic [12], herbicidal [13], and pesticidal [14] activity. Publications devoted to these problems have been summarized in a number of reviews [15-18].Of great interest among the investigated compounds are the nitro-substituted dihydropyrimidines. They readily undergo various chemical transformations, among which the unique ability to undergo recyclization to heterocyclic and carbocyclic compounds should be noted in particular.The interest in the nitrodihydropyrimidines is also due to the fact that these compounds represent the active principle or act as metabolites responsible for the physiological action of nitropyrimidines. Recently, products having antimicrobial [19] and antiviral [20][21][22] activity and also products suitable for the treatment of cardiovascular diseases [23-26] have been found among them. The present review is therefore devoted to the production, chemical transformations, and biological characteristics of dihydropyrimidines containing a nitro group at position 5 of the heterocycle. In addition, derivatives of furoxano [3,4d]pyrimidine with a nitro group inserted into the five-membered ring (which can be regarded as analogs of 5nitrodihydropyrimidines) are also included in the review. 5-Nitrodihydropyrimidines can be described by five structures, having one (1,4-, 1,6-, and 1,2-) or two (2,5-and 4,5dihydropyrimidine systems) geminal centers, the carbon atoms of which are characterized by sp 3 hybridization.1,4-1,6-1,2-2,5-4,5-The 5-nitro-l,2-, 5-nitro-l,4-, and 5-nitro-l,6-dihydropyrimidines are cyclic enamines, in which the electron pair of the sp3-hybridized nitrogen atom is in conjugation with the four 7r electron...

Etidronic Acid: a New and Efficient Catalyst for the Synthesis of Novel 5-Nitro-3,4-Dihydropyrimidin-2(1H)-Ones

“…When the reaction of the 1-(2-hydroxyphenyl)-2-nitroethanone 1 with various arylaldehydes 2a and urea 3 was conducted it was observed that the electron deficiency and nature of the substituents on the aromatic ring aldehydes effect the conversion rate; aromatic aldehydes having electron-withdrawing groups on the aromatic ring (Table 3, New and Efficient Catalyst for the Synthesis of Novel 5-Nitro-3,4-dihydropyrimidin-2(1H)-ones 283 entries 6,8,9) reacted faster than electron-donating groups (Table 3, entries 2, 11, 12). The synthesized compounds were characterized by spectroscopy analysis.…”

“…However, the reaction carried out under microwave irradiation gave excellent yields (entry 4, 2). The yield of desired product 4a was moderate when methanol and ethanol was used as solvent (entry [5][6][7][8] and in this case product 4a was separated by column chromatography over silica gel using hexane/EtOAc (7:3) as an eluent.…”

“…However, Substitution of NO 2 for COOAlk in the dihydropyridines alters their biological action. Reports reveal that nitro group functionalized dihydropyrimidines which might have potential biological activities were less studied [6].…”

“…Recently, many improved procedures have been reported using InBr 3 [8], InCl 3 [9], LiClO 4 [10], FeCl 3Á 6H2O or NiCl 2Á 6H2O [11], p-TsOH [12], LaCl 3Á 7H 2 O [13], IR radiation [14], Bi(OTf) 3 [15], La(OTf) 3 [16], BF 3 OEt 2 [17], ionic liquids (BMIm PF 6 and BMIm BF 4 ) [18], TEBA [19], natural HEU type zeolite [20], I 2 [21], N-bromosuccinimide (NBS) [22], polyaniline-bismoclite complex [23] and other Lewis acids [24] heteropoly acid [25], sulfated zirconia [26], Sr(NO 3 ) 2 [27], and covalently anchored sulfonic acid onto silica [28], PPE [29], Phosphoric acid [30]. However, some of the newer reported methods also suffer from drawbacks such as unsatisfactory yields, cumbersome product isolation procedures, and environmental pollution.…”

Antiarrhythmic activity of 4,6-di(het)aryl-5-nitro-3,4-dihydropyrimidin-(1H)-2-ones and its effects on arterial pressure in rats

“…8 At the same time, it was shown that nitro derivatives of dihydropyrimidinones (IV) are Ca antagonists or agonists depending upon character and position of a substituent in the Ar group having low acute toxicity. 9 …”