Synthesis and antihyperglycemic activity of novel 5-(naphthalenylsulfonyl)-2,4-thiazolidinediones

Abstract

A series of 5-(naphthalenylsulfonyl)-2,4-thiazolidinediones were synthesized and evaluated for antihyperglycemic activity in an insulin-resistant, genetically diabetic db/db mouse model of non-insulin-dependent diabetes mellitus (NIDDM). The sulfones could be synthesized by a novel, selective C-5 sulfonylation of dilithio-2,4-thiazolidinedione with appropriate sulfonyl chlorides. Within this series, naphthalene was found to be superior to other groups for eliciting antihyperglycemic activity, including the p-alkoxyphenyl group found in ciglitazone, a prototypical agent for this activity. Attachment of the 5-sulfonyl-2,4-thiazolidinedione moiety to the 2-naphthalene position led to optimum activity. Other linkers between the naphthalene and 2,4-thiazolidinedione rings, such as thio, methylene, oxy, and sulfinyl led to decreased antihyperglycemic activity. The best analogue, 5-(2-naphthalenylsulfonyl)-2,4-thiazolidinedione (AY-31,637) was equipotent to ciglitazone in two animal models of NIDDM.

Synthesis and biological activity evaluation of 5-pyrazoline substituted 4-thiazolidinones

“…The starting 3,5-diaryl-4,5-dihydro-1H-pyrazole [25], 5-bromothiazolidine-2,4-dione [26], and (2,4-dioxothiazolidine-5-ylidene)-acetyl chloride [27] were obtained according to the Table 2 Anticancer activity against a panel of approximately sixty tumor cell lines from nine different cancer types at 10-fold dilutions of five concentrations.…”

“…The starting 3,5-diaryl-4,5-dihydropyrazoles synthesized using known methods from appropriate chalcones [25] easily reacted with 5-bromothiazolidine-2,4-dione [26] yielding 5-(3-naphthalen-2-yl-5-aryl-4,5-dihydropyrazol-1-yl)-thiazolidine-2,4-dione 1a and 1b. It is known that chemical modification of the N3 position of thiazolidinone cycle has an essential influence on the antitumor activity [27,28].…”

3-(p-Nitrobenzyl)-1,3-thiazolidine-2,4-dione

“…Thiazolidine-2,4-dione is used as a starting material for the synthesis of drugs with antihyperglycemic activity (Zask et al, 1990). In heterocyclic chemistry, the thiazolidine-2,4-dione class is particularly important as a therapeutic agent and has been thoroughly investigated as a PPAR--agonist that led to the development of several insulin-sensitizing drugs for the treatment of type-2 diabetes (Blanchet & Zhu, 2004).…”

Solid solution of two diastereomers of [3a(R,S),7a(R,S)]-3-[(1′R)-1-phenylethyl]perhydro-1,3-benzothiazol-2-iminium chloride

“…A wide interest in thiazolidin-2-imines and related heterocycles is due to their pharmacological and biological activity such as local anesthetic, anti-seizure, anti-tubercular, anti-bacterial, anti-amoebic, anti-diabetic, anti-inflammatory, anti-oxidant and anti-fungal activity (Chaurasia, 1971;Eswaramoorthy et al, 1991;Zimenkovsky et al, 1999;Shankaran et al, 2004;Heinelt et al, 2004). Substituted 1,3-thiazolidines have also been explored as valuable starting materials for the preparation of more complex structures (Zask et al, 1990;Hwu et al, 1999;Jin & Kim, 2002). The most popular method to synthesize thiazolidines is the cyclization reaction of aziridines with heterocumulenes, such as phenyl isothiocyanate, in the presence of a catalyst [NaI; Campbell & Craig, 1980;Nadir & Basu, 1995; compounds of palladium(II); Baeg et al, 1995;Butter et al, 2000; or Bu 3 P; Wu et al, 2008].…”