85259-45-6

Upstream product

• 85259-08-1 (E)-3-[4-(2-Pyridin-2-yl-ethoxy)-phenyl]-acrylic acid 
• 103-74-2 2-(2-Hydroxyethyl)pyridine 
• 123-08-0 4-hydroxy-benzaldehyde 
• 85003-44-7 2-Chloro-3-[4-(2-pyridin-2-yl-ethoxy)-phenyl]-propionic acid methyl ester 
• 85002-52-4 4-<2-(2-pyridyl)ethoxy>nitrobenzene 
• 136401-96-2 4-(2-Pyridin-2-yl-ethoxy)-benzonitrile 
• 1194-02-1 4-fluorobenzonitrile 

Downstream Products

• 136401-63-3 5-(4-(2-(pyridin-2-yl)ethoxy)benzylidene)thiazolidine-2,4-dione 
• 1072082-05-3 5-(4-(2-(pyridin-2-yl)ethoxy)benzylidene)thiazolidine-2,4-dione 
• 85258-88-4 5-[4-(2-Pyridin-2-yl-ethoxy)-phenyl]-thiazolidine-2,4-dione 

Relevant academic research and scientific papers

NOVEL THIAZOLIDINEDIONE DERIVATIVE AND USE THEREOF

The present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and the uses thereof. More specifically, the present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and a pharmaceutical composition comprising the same. The novel thiazolidinedione derivatives of formula (I) according to the present invention can be effectively used for the prevention or treatment of cardiovascular disease, gastrointestinal disease and renal disease by inhibiting the activity of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that decomposes prostaglandins as well as useful for the prevention of hair loss and the stimulation of hair growth, and osteogenic stimulation and wound healing.

Synthesis and SAR of thiazolidinedione derivatives as 15-PGDH inhibitors

Prostaglandins have a short life in vivo because they are metabolized rapidly by oxidation to 15-ketoprostaglandins catalyzed by a cytosolic enzyme known as NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Previously, CT-8, a thiazolidinedione analogue, was found to be a potent inhibitor of 15-PGDH. Structure-activity analysis indicated that the N-methylation of thiazolidine-2,4-dione, CT-8, abolished the inhibitory activity, whereas the introduction of an ethyl hydroxyl group at amine in CT-8 still had a good inhibitory effect. Based on the structures of the thiazolidinediones analogues and inhibitory activity, a range of benzylidene thiazolidinedione derivatives were synthesized with different substituents on the phenyl ring and their inhibitory activity was evaluated. Replacement of the cyclohexylethyl group of CT-8 with the hetero five-member ring increased the inhibitory potency. However, replacement of the cyclohexylethyl group with a hetero six-member ring decreased the inhibitory potency significantly. It was found that compound 2 (5-(4-(2-(thiophen-2-yl)ethoxy)benzylidene)thiazolidine-2,4-dione) was the most potent inhibitor that was effective in the nanomolar range.

Studies on antidiabetic agents. X. Synthesis and biological activities of pioglitazone and related compounds

Various analogues of a new antidiabetic agent, pioglitazone (AD-4833, U-72107), were synthesized in order to study in more detail the structure-activity relationships of this class of drug. 5-(4-Pyridylalkylthiobenzyl)-2,4-thiazolidinediones (I), this-analogues of pioglitazone, were prepared via Meerwein arylation of the alkylthioanilines (IV). 5-(4-Pyridylalkoxybenzylidene)-2,4-thiazolidinediones (IIa) and related heterocyclic analogues (IIb) were synthesized by Knoevenagel condensation of the aldehydes (VIII) with the corresponding azolidinones. Compounds I and II were evaluated for hypoglycemic and hypolipidemic activity in genetically obese and diabetic yellow KK (KKA(y)) mice. Several 5-[4-[2-(2-pyridyl)ethoxy]-benzylidene]-2,4-thiazolidinediones (IIa) were equipotent to pioglitazone. However, the thia-analogues (I) and the benzylideneheterocycles (IIb) had decreased activity. Catalytic hydrogenation of the 5-benzylidene analogue (14) was found to be a convenient new synthetic method for pioglitazone. The configuration of 14 is also discussed.