New azole antifungals.: 2.: Synthesis and antifungal activity of heterocyclecarboxamide derivatives of 3-amino-2-aryl-1-azolyl-2-butanol

被引：44

作者：

Bartroli, J ^{[1
]}

Turmo, E ^{[1
]}

Alguero, M ^{[1
]}

Boncompte, E ^{[1
]}

Vericat, ML ^{[1
]}

Conte, L ^{[1
]}

Ramis, J ^{[1
]}

Merlos, M ^{[1
]}

García-Rafanell, J ^{[1
]}

Forn, J ^{[1
]}

机构：

[1] J Uriach & Cia SA, Res Ctr, E-08026 Barcelona, Spain

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1998年 / 41卷 / 11期

关键词：

D O I：

10.1021/jm970726e

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 92 azole antifungals containing an amido alcohol unit was synthesized. The nature and substitution of the amide portion was systematically modified in search of improved antifungal activity, especially against filamentous fungi. The compounds were tested in vitro against a variety of clinically important pathogens and in vivo (po) in a murine candidosis model. Thiazole and thiophene carboxamides carrying both a substituted phenyl ring and a small alkyl. group were best suited for activity against filamentous fungi. In a subset of these compounds, the amide portion was conformationally locked by means of a pyrimidone ring and it was proven that only an orthogonal orientation of the phenyl ring yields bioactive products. A tendency to display long plasma elimination half-lives was observed in both series. Two compounds, 74 and 107, representative of the open and cyclic amides, respectively, were chosen for further studies, based on their excellent activity in in vivo murine models of candidosis and aspergillosis. This work describes the SARs found within this series. The next paper displays the results obtained in a related series of compounds, the quinazolinones.

引用

页码：1855 / 1868

页数：14

共 44 条

[1]

ABDELLATEEF MF, 1972, ROCZ CHEM, V46, P1647

[2]

ALBEROLA A, 1990, CHEM COMMUN, V20, P2337

[3] SYNTHESIS AND ANTIFUNGAL ACTIVITY OF NEW AZOLE DERIVATIVES CONTAINING AN N-ACYLMORPHOLINE RING [J].