338751-59-0

Upstream product

• 103-72-0 phenyl isothiocyanate 
• 62-53-3 aniline 
• 22288-78-4 Methyl 3-aminothiophene-2-carboxylate 
• 468096-43-7 methyl 3-[(anilinocarbonothioyl)amino]thiophene-2-carboxylate 

Downstream Products

• 468096-47-1 2-{[2-(diethylamino)ethyl]thio}-3-phenylthieno[3,2-d]pyrimidin-4(3H)-one 
• 468096-50-6 3-phenyl-2-[(2-piperidin-1-ylethyl)thio]thieno[3,2-d]pyrimidin-4(3H)-one 

Relevant academic research and scientific papers

Synthesis of 4-phenylthieno[2, 3-e][1, 2, 4]triazolo[4, 3-a]pyrimidine-5 (4H)-one derivatives and evaluation of their anti-inflammatory activity

A series of 4-phenylthieno[2, 3-e][1, 2, 4]triazolo[4, 3-a]pyrimidine-5 (4H)-ones (5a-p) with triazole or other heterocyclic substituents (6-11) was synthesized and the compounds were evaluated for their anti-inflammatory activity using the xylene-induced ear-edema test. Pharmacological analyses showed that the compound 4- (4-chlorophenyl)thieno[2, 3-e][1, 2, 4]triazolo[4, 3-a]pyrimidine- 5 (4H)-one (5m) exhibited the greatest anti-inflammatory activity (50.48% inhibition, 30 min after intraperitoneal administration) and was more potent than the reference drug, indomethacin. The peak activity of 5m was observed 4 h after oral administration, and it showed a higher anti-inflammatory activity than indomethacin did at a dose of 100 mg/kg.

CODES, a novel procedure for ligand-based virtual screening: PDE7 inhibitors as an application example

Phosphodiesterase (PDE) 7 is a high affinity cAMP-specific PDE whose functional role in T-cells has been the subject of some controversy. Recent findings on tissue distribution, however, support the hypothesis that PDE7 could be a good target for the treatment of airway diseases, T-cell related diseases or central nervous system (CNS) disorders. Therefore, the identification of selective inhibitors targeted against PDE7 enzyme has become an attractive area of research. We report here the first use of the descriptors generated by the CODES program for ligand-based virtual screening. This program codifies molecules from a topological point of view and the generated descriptors are related to the chemical nature of the atoms, the atomic bonds and the connectivity with the rest of the molecule. They are also able to distinguish among stereoisomers. By using this approach, 173 compounds were codified, and their similarity with the reference compound was analysed. Based on the analysis, new potential PDE7 inhibitors have been identified, synthesized and biologically evaluated confirming that CODES descriptors are valid for ligand-based virtual screening and provided new lead compounds for further optimization as potent and selective PDE7 inhibitors.

Synthesis and spasmolytic action of 2-substituted thienopyrimidin-4-one derivatives

In the search for novel compounds to treat disorders of smooth muscle function, efforts have focused on some 2-substituted thieno[2,3-d]pyrimidin-4-one derivatives that show interesting spasmolytic action. Our laboratories have developed a new series of quaternary salts of 2-substituted thieno[2,3-d]pyrimidin-4-one and thieno[3,2-d]pyrimidin-4-one isomers with therapeutic potential. These substances were prepared starting from simple derivatives of thiophene. Their spasmolytic activity was evaluated on transmurally stimulated guinea-pig ileum. The most active compounds (IC50 1.12-2.71 μM) 7f-7h, 12d and 12f had the terminal piperidino nucleus in the thioalkyl chain and lacked two methyl groups in the thiophene ring. Their relaxant activity on the isolated ileum was potential (approx. 20-25%) by phosphodiesterase inhibitors. Compounds 7f-h, 12d and 12f were less effective in inhibiting contractions of the guinea-pig ileum induced by acetylcholine (IC50 26.7-41.4 μM) or histamine (IC50 41.5-63.4 μM) and had a moderate binding activity to muscarinic receptors in membrane homogenates from the rat heart (M2 sites; pKi values between 5.55±0.08 and 5.14±0.12; n = 3) and submaxillary gland (M3 sites; pKi values between 6.15±0.07 and 5.76±0.08; n = 3). Action involving soluble guanylyl cyclase or any potential binding to guinea-pig ventricular L-type calcium channels was not considered likely. It is concluded that at least two different mechanisms of action contribute to their spasmolytic activity.