Homo- and heterodimeric Smac mimetics/IAP inhibitors as in vivo-active pro-apoptotic agents. Part I: Synthesis

被引：18

作者：

Manzoni, Leonardo ^{[2
]}

Belvisi, Laura ^{[1
]}

Bianchi, Aldo ^{[3
]}

Conti, Annalisa ^{[4
]}

Drago, Carmelo ^{[3
]}

de Matteo, Marilenia ^{[3
]}

Ferrante, Luca ^{[3
]}

Mastrangelo, Eloise ^{[5
,6
]}

Perego, Paola ^{[4
]}

Potenza, Donatella ^{[1
]}

Scolastico, Carlo ^{[3
]}

Servida, Federica ^{[7
]}

Timpano, Gabriele ^{[3
]}

Vasile, Francesca ^{[1
]}

Rizzo, Vincenzo ^{[3
]}

Seneci, Pierfausto ^{[1
,3
]}

机构：

[1] Univ Milan, Dipartimento Chim, I-20133 Milan, Italy

[2] CNR, ISTM, I-20133 Milan, Italy

[3] CISI Scrl, I-20138 Milan, Italy

[4] Fdn IRCCS Ist Nazl Tumori, Dipartimento Oncol Sperimentale & Med Mol, I-20133 Milan, Italy

[5] Univ Milan, Dipartimento Biosci, I-20133 Milan, Italy

[6] Univ Milan, CNR IBF, I-20133 Milan, Italy

[7] Univ Milan, Fdn Matarelli, Dipartimento Farmacol Chemioterapia & Tossicol Me, I-20129 Milan, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 22期

关键词：

IAP inhibitors; Smac mimetics; Apoptosis; Oncology; Peptidomimetics; X-LINKED INHIBITOR; NF-KAPPA-B; STRUCTURAL BASIS; IAP PROTEINS; RATIONAL DESIGN; CELL-DEATH; CANCER; POTENT; XIAP; PATHWAYS;

D O I：

10.1016/j.bmc.2012.09.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Novel pro-apoptotic, homo-and heterodimeric Smac mimetics/IAPs inhibitors based on the N-AVPI-like 4-substituted 1-aza-2-oxobicyclo[5.3.0]decane scaffold were prepared from monomeric structures connected through a head-head (8), tail-tail (9) or head-tail (10) linker. The selection of appropriate decorating functions for the scaffolds, and of rigid and flexible linkers connecting them, is described. The synthesis, purification and analytical characterization of each prepared dimer 8-10 is thoroughly described. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：6687 / 6708

页数：22

共 2 条

[1] Dimeric Smac mimetics/IAP inhibitors as in vivo-active pro-apoptotic agents. Part II: Structural and biological characterization
Lecis, Daniele
Mastrangelo, Eloise
Belvisi, Laura
Bolognesi, Martino
Civera, Monica
Cossu, Federica
De Cesare, Michelandrea
Delia, Domenico
Drago, Carmelo
Manenti, Giacomo
Manzoni, Leonardo
Milani, Mario
Moroni, Elisabetta
Perego, Paola
Potenza, Donatella
Rizzo, Vincenzo
Scavullo, Cinzia
Scolastico, Carlo
Servida, Federica
Vasile, Francesca
Seneci, Pierfausto
BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (22) : 6709 - 6723
[2] Rational design, synthesis and characterization of potent, drug-like monomeric Smac mimetics as pro-apoptotic anticancer agents
Bianchi, Aldo
Ugazzi, Marcello
Ferrante, Luca
Lecis, Daniele
Scavullo, Cinzia
Mastrangelo, Eloise
Seneci, Pierfausto
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (06) : 2204 - 2208

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