Synthesis and Antifungal Activity of Novel Thiazole-Containing Triazole Antifungals. II. Optically Active ER-30346 and Its Derivatives.

Abstract

A series of novel thiazole-containing triazole antifungals was synthesized and evaluated for antifungal activity against a variety of clinically isolated pathogenic fungi in vitro and against systemic candidosis in vivo. These compounds showed potent antifungal activities in vitro and in vivo. In particular, (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4- difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (12g; ER-30346) showed potent and well-balanced in vitro activities and potent in vivo efficacy, and had a good safety profile.

Development and Validation of a Preclinical Food Effect Model

“…For the HIV attachment inhibitor24–26 and Factor Xa inhibitor,27 the lowest strength clinical dosage form was used. To extend the applicability of the model for use in drug discovery, bulk drug in capsule was used for ravuconazole28–31 and metformin. For these studies, a size 12 capsules was filled with 150 mg and 120 mg of dry powder, respectively.…”

Synthesis of condensed thiazoles. (Review)

“…The thiazolopyridine derivative 122 was also obtained from a thiourea of the pyridine series 121 by treatment with HBr in DMSO [91]. 5-Amino-2-chloropyridine (123) was converted into 2-aminothiazolopyridine 124 with a yield of 91% by reaction with sodium thiocyanate in the presence of bromine in acetic acid [92]. The cyclization of pyridinedithiocarbamate 127 with alkali in ethanol gives a mixture of thiazolopyridinethiol 128 (86%) and N,N-diisopropylthiazolopyridine-2-amine (129) (14%) [93,94].…”

Synthesis and Antifungal Screening of 2‐(2‐Aryl‐4‐methyl‐thiazol‐5‐yl)‐5‐((2‐aryl/benzylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole Derivatives

“…Fungal infections have increased dramatically in recent years and serious threat to human health in immunocompromised patients . Azoles are an important class of five‐member heterocyclic compounds, which have been the subject of great interest because of its wide range of antifungal activity . Thiazole ring is an important pharmacophore, and its coupling with other rings could furnish new biologically active compounds.…”