Synthesis of 3,4-dihydro-4-oxothieno[2,3-d]pyrimidine-2-carboxylates, a new series of orally active antiallergy agents

Abstract

A series of novel 3,4-dihydro-4-oxothieno[2,3-d]pyrimidine-2-carboxylic acid derivatives has been prepared and tested for antiallergenic activity. Members of the series, including both carboxylic acid salts and esters, have been found to exhibit oral activity in the rat passive cutaneous anaphylaxis (PCA) test. Activity is optimized by H or CH3 substitution at the 5 position and lower alkyl groups at the 6 position. Ethyl 6-ethyl-3,4-dihydro-4-oxothieno-[2,3-d]pyrimidine-2-carboxylate and 3,4-dihydro-5-methyl-6-(2-methylpropyl)-4-oxothieno[2,3-d]pyrimidine-2-carboxylic acid dipotassium salt were the most potent of the esters and salts, respectively. Such compounds have been shown to have a duration of action of up to 4 h in the PCA test and to inhibit both histamine release from rat peritoneal mast cells in vitro and allergen-induced bronchospasm in the rat lung.

Gewald reaction: synthesis, properties and applications of substituted 2-aminothiophenes

“…119 Thieno[2, 3-d]pyrimidine derivatives show pronounced antiinflammatory 120 , anti-tumor 121 , radioprotective and anti-convulsing activity. 122 The pharmacological versatility of the above system also present in substances with depressant or sedative properties 123 and compounds used for therapy of malaria 124 , tuberculosis 125 , Parkinson´s disease 126 and other diseases were designed. 127 Their synthesis relies on the annulation of pyrimidine ring to five-membered thiophenes.…”

“…Because the structure-based drug design program through substituted 2-aminothiophenes has been investigated broadly, up to this date there are many other research works dealing with the synthesis, pharmacology and application of thiophene-based structures in medicinal chemistry. 7,[12][13][14]36,37,51,69,100,101,[119][120][121][122][123][124][125][126][127] It is no doubt, that this area of Gewald-like thiophene derivatives exhibits the highest progress in a scope and utilization.…”

Anti-inflammatory and immunomodulatory effects of RDV-8 [C18H22N2O2S (ethyl 1-butyl-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidine-5-carboxylate)] in a rat model of induced pleurisy and in vitro lymphoproliferation

“…Besides the antineoplastic activity previously described (Shimizu et al 1995), many biological properties were attributed to this class of compounds, such as antiviral (Saladino et al 2002), anti-hypertensive (Salimbeni et al 1995), hypoglycemic (Madhavan et al 2002), anticonvulsive (White et al 2004), anti-histaminic (Temple et al 1979) and anti-inflammatory (Modica et al 2000). In recent researches, pyrimidines derivatives and similar substances containing a carbonyl group in the position of an amino group present in the C 4 heterocyclic ring would further increase the pharmacological potential, besides presenting low toxicity (Anjos et al 2008).…”

Synthesis of new iso-C-nucleoside analogues from 2-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-yl)ethanal

“…1 The corresponding 5-carboxamido-4-hydroxy-3-(b-D D-ribofuranosyl)thiophene-2-carbonic acid derivatives were investigated as virucides and virostatic agents. 2 Furthermore, thieno [2,3-d]pyrimidine derivatives 3 showed interesting biological properties including antihypertensive, 4 antiallergenic, 5 antitumour, 6 antiviral, 6 anti-HIV-1 6 and analgesic 7 activities. A few examples of thieno [2,3-d]pyrimidine nucleosides are known.…”