Synthesis of 5-(4-Alkylsulfanyl-[1, 2, 5]Thiadiazol-3-yl)-3-Methyl-1, 2, 3, 4-Tetrahydropyrimidine Oxalate Salts and their Evaluation as Muscarinic Receptor Agonists

Abstract

The synthesis and biological test of 5-(4-alkylsulfanyl-[1, 2, 5]thiadiazol-3-yl)-3-me-thyl-1, 2, 3, 4-tetrahydropyrimidine oxalate salts 7 as muscarinic receptor agonists are described. The key intermediate 4 was obtained by a modified Strecker reaction and cyclization, and the 3-methyl-1, 2, 3, 4-tetrahydropyrimidines were obtained by subsequent substitution, quarternization, and reduction. The final products 7 were obtained as oxalic acid salts. The prepared compounds were examined in vitro for their binding affinities to the cloned human muscarinic receptor by the [(3)H]-NMS binding assay.

Recent Developments in the Synthesis and Applications of 1,2,5-Thia- and Selenadiazoles. A Review

“…The reaction of aminoacetonitrile and its aliphatic, aromatic, and heterocyclic derivatives with sulfur monochloride in dimethylformamide at room temperature gave 3-chloro-1,2,5-thiadiazoles 41 in low to moderate yields (Scheme 19). 35,[50][51][52][53][54][55][56] Often the aminoacetonitriles were not isolated, but characterized and used directly in the preparation of chlorodithiazoles; the reported yields were based on the aldehyde precursors. 57,58 The mechanism for 1,2,5-thiadiazole formation was proposed in the 1960s, 35 it includes the formation of the N-chlorodithio intermediate 42 followed by chlorination of the nitrile function, ring closure, addition of the second molecule of sulfur monochloride, and formation of the heteroaromatic 1,2,5-thiadiazole cycle (Scheme 20).…”

A novel and efficient synthesis of fluoroalkylated multifunctional 1,2,3,4-tetrahydropyrimidines

“…1,2,3,4-Tetrahydropyrimidine ring is an important unit in both natural and synthetic organic compounds, and many compounds containing it show interesting biological activities [1][2][3][4][5][6][7][8][9]. It is well-known that the introduction of fluorine atom or fluoroalkyl groups into heterocyclic compounds may have a profound influence on their biological and physical properties [10].…”