Synthesis and antimicrobial activity of new amino derivatives of pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidine

Abstract

Annulated thienopyrimidine derivatives attracted big interest of the scientific community due to their broad spectrum of biological activities among which are the inhibition of phosphodiesterase, antiproliferative and antimicrobial activities. As a continuation of our studies on the synthesis and biological activity of fused thieno[3,2-d]pyrimidine derivatives, the goal of this paper is the synthesis and study of the properties of compounds containing different heterocycles such as fused thieno[2,3-b]pyridine and tetrazolo[1,5-c]pyrimidine in the same molecule. Thus, starting from the ethyl 1-amino-5-isopropyl-8,8-dimethyl-8,9-dihydro-6H-pyrano[4,3-d]thieno[2,3-b]pyridine-2-carboxylate 1, efficient methods for obtaining new 8-amino-5-isopropyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidines 6 and thieno[2,3-e]tetrazolo[1,5-c]pyrimidine 8 are described. The spectroscopic results showed that compound 8 in the solid state is exclusively in the tetrazolo tautomeric form, while in solution an azide-tetrazole equilibrium is present 8A/T. The possible antimicrobial activity of newly synthesized compounds against some gram-positive and gram-negative bacilli strains has been evaluated. The biological tests evidenced that some of them showed promising antimicrobial activity. Two compounds showed similar activity to the one of the used reference drug. The study of structure-activity relationships revealed that the activity of a compound depends mostly on the nature of substituent R1R2. According to the predicted docking studies our compounds could be DnaG inhibitors.

Synthesis of New Heterocyclic Systems: Pyrido[3′,2′:4,5]thieno(furo)[2,3‐e][1,2,4]triazolopyrimidines and an Unusual ANRORC Rearrangement in the Fused Pyrimidine Series

“…As starting compounds ethyl 1-aminofuro(thieno) [2,3-b] pyridine-2-carboxylates 1 aÀ h [8,13À 15] were used ( Figure 2). Compounds 1 aÀ h [8] reacted with benzoyl isothiocyanate in benzene, giving the polyfunctionalized thioureido derivatives 2 a-h [12,16,17] prone to furnish further cyclization reaction (Scheme 1, Table 1). Thus, compounds 2 by intramolecular cyclization under the action of potassium hydroxide in ethanol furnished the 9(10)-thioxopyrido[3',2':4,5]thieno(furo) [3,2-d]pyrimidin-7(8)-ones 3 a-h [16] in very high yields (Scheme 1).…”

“…Further, with the aim of synthesizing condensed triazoles at the [a] side of the pyrimidine ring we firstly alkylated the 9(10)thioxopyrido[3',2':4,5]thieno(furo)[3,2-d]pyrimidin-7(8)-ones 3 ah with methyl iodide (see Scheme 1), thus obtaining at low temperatures 'only' compounds 4 aÀ h [16,17] (methylation at the thiol group, id est at the more nucleophilic center) and then by further methylation at 35À 40°C the 8(9)-methyl-9(10)-(methylthio)pyrido[3',2':4,5]thieno(furo)[3,2-d]pyrimidin-7(8)ones 5 aÀ h [16] (methylation at the pyrimidinic N-8, the less nucleophilic center), in line with a procedure previously described by us (Scheme 1, Table 1). [16] Regarding the reactivity of compounds 5 with hydrazine it was observed that they stay unchanged by long refluxing (25À 30 h) with hydrazine hydrate in ethanol as well as by using an excess of hydrazine hydrate as a solvent.…”

New strategy of synthesis, characterization, theoretical study and inhibition effect on mild steel corrosion in acidic solution

“…Heterocyclic systems have recently attracted much attention because they have various abilities such as anti-microbial, anti-tumor, anti-epileptic, antihistaminic, anti-oxidant and anti-inflammatory actions [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] ; and they are being used as lead compounds for drug development 18 . As the results of several recent studies have indicated that some heterocyclic compounds derivatives synthesized have a diversity of useful biological effects including antibacterial, antifungal, analgesic, antiviral, anticancer, antihypertensive, anticonvulsant, and anti-diabetic properties [19][20][21][22][23][24][25] . They are also widely utilized as a building block in numerous materials and compounds 26 .…”

Synthesis, Antitumor Activity, and Docking Analysis of New Pyrido[3’,2’:4,5]furo(thieno)[3,2-d]pyrimidin-8-amines

“…We have previously reported on the synthesis and biological activity of some amino derivatives of condensed furo- and thieno [3,2- d ]pyrimidines [12,13,14,15,16]. Particularly, the studies showed that these compounds are distinguished by high anticonvulsant [12,13,14] and antibacterial activity [15,16]. Continuing our studies in the field of searching for new heterocyclic compounds of biological interest, herein we report on the synthesis and antitumor activity of new amino derivatives of pyrido[3′,2′:4,5](furo)thieno[3,2- d ]pyrimidines as well as new heterocyclic systems: furo[2,3- e ]imidazo[1,2- c ]pyrimidine and furo[2,3- e ]pyrimido[1,2- c ]pyrimidine.…”