Abstract
A new and efficient procedure has been designed for the preparation of 6-arylmethylene-amino-2-alkyl sulfonyl-pyrimidine. The first alkylthio group was introduced into the pyrimidine ring by S-alkylation. The introduction of the second one was successfully achieved using the phosphorous oxychloride method to afford 4-chloro-2-alkylthio-pyrimidines. Subsequent nucleophilic displacement by the corresponding alkylamines followed by glycoside bromide addition conveniently gave a series of the target compounds. Thus, the two same or different alkylamino groups were easily introduced into the pyrimidine ring through the two different approaches. The human anti-platelet aggregation activity of the newly synthesized compounds was also described.
Highlights
Pyrimidines play an essential role in several biological processes and have considerable chemical and pharmacological importance in terms that the pyrimidine ring can be found in nucleoside antibiotics, anti-bacterial and cardiovascular [1,2,3,4,5,6,7,8,9]
There have been active attempts to develop the antagonist of P2Y receptors by employing adenine nucleotide derivatives containing two phosphate groups, i.e., adenosine-3’,5’-bis-phosphate analogues, as P2Y1 receptor antagonists [12,13] and 4-alkoxyl-2-alkylthio-6-aminopyrimidine derivatives as P2Y12 receptor antagonists [14]
According to the results observed with the former pyrimidine derivatives as platelet antiaggregating agents, the substitution of these compounds at the 4 position could lead to new PDGFR or EGFR pathway inhibitors
Summary
Pyrimidines play an essential role in several biological processes and have considerable chemical and pharmacological importance in terms that the pyrimidine ring can be found in nucleoside antibiotics, anti-bacterial and cardiovascular [1,2,3,4,5,6,7,8,9]. As for adenine nucleotide analogues against P2T receptor, there’s effective enhancement of the activity by N-mono-alkylation at the 6-position of the adenine moiety [15] Considering such findings on the structure of the antagonist candidates, we achieved one hypothesis that N-monoalkylation of pyrimidine compounds might increase anti-platelet aggregation activity. We designed to introduce another thio-nucloside group into the pyrimidine ring As it is well known, the introduction of alkyl/arylthio groups into the pyrimidine ring is commonly achieved through either the alkylation of thiol groups or the nucleophilic substitution of halogens by alkylmer-captides. These processes must be conducted under harsh condi-. We describe the details of the convenient synthesis and the evaluation results of all the synthesized compounds as human platelet aggregation inhibitors
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