Oxadiazole-carbonylaminothioureas as SIRT1 and SIRT2 inhibitors

被引：77

作者：

Huhtiniemi, Tero ^{[1
]}

Suuronen, Tiina

Rinne, Valtteri M. ^{[1
]}

Wittekindt, Carsten ^{[1
]}

Lahtela-Kakkonen, Maija ^{[1
]}

Jarho, Elina ^{[1
]}

Wallen, Erik A. A. ^{[1
]}

Salminen, Antero

Poso, Antti ^{[1
]}

Leppanen, Jukka ^{[1
]}

机构：

[1] Univ Kuopio, Dept Pharmaceut Chem, FIN-70211 Kuopio, Finland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 15期

关键词：

D O I：

10.1021/jm800639h

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new inhibitor for human sirtuin type proteins I and 2 (SIRTI and SIRT2) was discovered through virtual database screening in search of new scaffolds. A series of compounds was synthesized based on the hit compound (3-[[3-(4-tert-butylphenyl) 1,2,4-oxadiazole5 -carbonyl I amino] -I - [3-(tri fluoromethy I)phenyl] thiourea). The most potent compound in the series was nearly as potent as the reference compound (6-chloro-2,3,4,9-tetrahydro-IH-carbazole-l-carboxamide).

引用

页码：4377 / 4380

页数：4

共 22 条

[1] Identification of a small molecule inhibitor of Sir2p [J].

Bedalov, A ;

Gatbonton, T ;

Irvine, WP ;

Gottschling, DE ;

Simon, JA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (26) :15113-15118

[2] Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases [J].

Borra, MT ;

Langer, MR ;

Slama, JT ;

Denu, JM .

BIOCHEMISTRY, 2004, 43 (30) :9877-9887

[3]

*CAMBR CRYST DAT C, GOLD V 3 0

[4] Phloroglucinol derivatives guttiferone G, aristoforin, and hyperforin:: Inhibitors of human sirtuins SIRT1 and SIRT2 [J].

Gey, Claudia ;

Kyrylenko, Sergiy ;

Hennig, Lothar ;

Nguyen, Lien-Hoa D. ;

Buettner, Anita ;

Pham, Hung D. ;

Giannis, Athanassios .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2007, 46 (27) :5219-5222

[5] Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes [J].

Heltweg, B ;

Gatbonton, T ;

Schuler, AD ;

Posakony, J ;

Li, HZ ;

Goehle, S ;

Kollipara, R ;

DePinho, RA ;

Gu, YS ;

Simon, JA ;

Bedalov, A .

CANCER RESEARCH, 2006, 66 (08) :4368-4377

[6] Comparative and pharmacophore model for deacetylase SIRT1 [J].

Huhtiniemi, Tero ;

Wittekindt, Carsten ;

Laitinen, Tuomo ;

Leppanen, Jukka ;

Salminen, Antero ;

Poso, Antti ;

Lahtela-Kakkonen, Maija .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2006, 20 (09) :589-599

[7] N,N′-bisbenzylidenebenzene-1,4-diamines and N,N′-bisbenzylidenenaphthalene-1,4-diamines as sirtuin type 2 (SIRT2) inhibitors [J].

Kiviranta, Paivi H. ;

Leppanen, Jukka ;

Kyrylenko, Sergiy ;

Salo, Heikki S. ;

Lahtela-Kakkonen, Maija ;

Tervo, Anu J. ;

Wittekindt, Carsten ;

Suuronen, Tiina ;

Kuusisto, Erkki ;

Jarvinen, Tomi ;

Salminen, Antero ;

Poso, Antti ;

Wallen, Erik A. A. .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (26) :7907-7911

[8] N-(3-(4-hydroxyphenyl)-propenoyl)-amino acid tryptamides as SIRT2 inhibitors [J].

Kiviranta, Paivi H. ;

Leppanen, Jukka ;

Rinne, Valtteri M. ;

Suuronen, Tiina ;

Kyrylenko, Olga ;

Kyrylenko, Sergly ;

Kuusisto, Erkki ;

Tervo, Anu J. ;

Jarvinen, Tomi ;

Salminen, Antero ;

Poso, Antti ;

Wallen, Erik A. A. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (09) :2448-2451

[9] Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein deacetylase (sirtuin) inhibitors [J].

Mai, A ;

Massa, S ;

Lavu, S ;

Pezzi, R ;

Simeoni, S ;

Ragno, R ;

Mariotti, FR ;

Chiani, F ;

Camilloni, G ;

Sinclair, DA .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (24) :7789-7795

[10] Microplate filtration assay for nicotinamide release from NAD using a boronic acid resin [J].

McDonagh, T ;

Hixon, J ;

DiStefano, PS ;

Curtis, R ;

Napper, AD .

METHODS, 2005, 36 (04) :346-350

← 1 2 3 →