Exploring isoxazoles and pyrrolidinones decorated with the 4,6-dimethoxy-1,3,5-triazine unit as human farnesyltransferase inhibitors

被引：8

作者：

Lucescu, Liliana ^{[1
]}

Ghinet, Alina ^{[1
,2
,3
]}

Shova, Sergiu ^{[4
]}

Magnez, Romain ^{[5
]}

Thuru, Xavier ^{[5
]}

Farce, Amaury ^{[2
,6
]}

Rigo, Benoit ^{[2
,3
]}

Belei, Dalila ^{[1
]}

Dubois, Joelle ^{[7
]}

Bicu, Elena ^{[1
]}

机构：

[1] AI I Cuza Univ Iasi, Fac Chem, Bd Carol I 11, Iasi 700506, Romania

[2] Univ Lille, CHRU Lille, Fac Med Pole Rech, LIRIC,INSERM,U995, Lille, France

[3] UC Lille, Yncrea Hauts De France, Lab Chim Durable & Sante Hautes Etud Ingn HEI, Lille, France

[4] Petru Poni Inst Macromol Chem, Iasi, Romania

[5] Univ Lille, UMR S 1172, JPARC, Ctr Rech Jean Pierre AUBERT Neurosci & Canc, Lille, France

[6] Fac Sci Pharmaceut & Biol Lille, Lille, France

[7] CNRS, UPR2301, Inst Chim Subst Nat, Ctr Rech Gif, Gif Sur Yvette, France

来源：

ARCHIV DER PHARMAZIE | 2019年 / 352卷 / 05期

关键词：

antitumor compound; cycloaddition; farnesyltransferase; inhibitor; isoxazole; pyrrolidine; triazine; ONE-POT SYNTHESIS; BIOLOGICAL EVALUATION; AEROBIC OXIDATION; PRIMARY AMINES; DERIVATIVES; TRIAZINE; DISCOVERY; ANALOGS; AGENTS; SERIES;

D O I：

10.1002/ardp.201800227

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Unprecedented triazinyl-isoxazoles were afforded via an effective cycloaddition reaction between nitrile oxides and the scarcely described 2-ethynyl-4,6-dimethoxy-1,3,5-triazine as dipolarophile. The biological evaluation of the newly synthesized compounds showed that the inhibition of human farnesyltransferase by zinc complexation could be improved with triazine-isoxazole moieties. The replacement of the isoxazole unit by a pyrrolidin-2-one was detrimental to the inhibitory activity while the pyrrolidin-2-thione derivatives conserved the biological potential. The potential of selected compounds to disrupt protein farnesylation in Chinese hamster ovary (CHO) cells transfected with pEGFP-CAAX was also evaluated.

引用

页数：11

共 71 条

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