Design and synthesis of macrocyclic inhibitors of phosphatase Cdc25B

被引：26

作者：

Bäurle, S ^{[1
]}

Blume, T ^{[1
]}

Günther, J ^{[1
]}

Henschel, D ^{[1
]}

Hillig, RC ^{[1
]}

Husemann, M ^{[1
]}

Mengel, A ^{[1
]}

Parchmann, C ^{[1
]}

Schmid, E ^{[1
]}

Skuballa, W ^{[1
]}

机构：

[1] Schering AG, Res Ctr Europe, D-13342 Berlin, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 07期

关键词：

steroids; macrocycles; phosphatases; molecular modeling; templates;

D O I：

10.1016/j.bmcl.2004.01.052

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Based on molecular modeling studies, macrocyclic inhibitors of phosphatase cdc25B were synthetically derived from steroids. A preliminary SAR for this new template was elaborated. A series of compounds shows inhibition of cdc25B in the low micromolar range and good selectivity versus other phosphatases. The compounds did not show a significant antiproliferative effect in MaTu or HaCaT cells. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：1673 / 1677

页数：5

共 38 条

[1] From rigidity to conformational flexibility:: Macrocyclic templates derived from ansa-steroids [J].

Bäurle, S ;

Blume, T ;

Mengel, A ;

Parchmann, C ;

Skuballa, W ;

Bäsler, S ;

Schäfer, M ;

Sülzle, D ;

Wrona-Metzinger, HP .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (33) :3961-3964

[2] The Protein Data Bank [J].

Berman, HM ;

Westbrook, J ;

Feng, Z ;

Gilliland, G ;

Bhat, TN ;

Weissig, H ;

Shindyalov, IN ;

Bourne, PE .

NUCLEIC ACIDS RESEARCH, 2000, 28 (01) :235-242

[3]

Broggini M, 2000, ANTICANCER RES, V20, P4835

[4]

B┬u├▒urle, 2003, ANGEW CHEM, V115, P4091

[5]

CHOWDHURY PK, 1987, LIEBIGS ANN CHEM, P1095

[6] Regulating mammalian checkpoints through Cdc25 inactivation [J].

Donzelli, M ;

Draetta, GF .

EMBO REPORTS, 2003, 4 (07) :671-677

[7] Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene [J].

Elchebly, M ;

Payette, P ;

Michaliszyn, E ;

Cromlish, W ;

Collins, S ;

Loy, AL ;

Normandin, D ;

Cheng, A ;

Himms-Hagen, J ;

Chan, CC ;

Ramachandran, C ;

Gresser, MJ ;

Tremblay, ML ;

Kennedy, BP .

SCIENCE, 1999, 283 (5407) :1544-1548

[8] Cdc25 cell-cycle phosphatase as a target of c-myc [J].

Galaktionov, K ;

Chen, XC ;

Beach, D .

NATURE, 1996, 382 (6591) :511-517

[9] CDC25 PHOSPHATASES AS POTENTIAL HUMAN ONCOGENES [J].

GALAKTIONOV, K ;

LEE, AK ;

ECKSTEIN, J ;

DRAETTA, G ;

MECKLER, J ;

LODA, M ;

BEACH, D .

SCIENCE, 1995, 269 (5230) :1575-1577

[10]

HILLIG RC, UNPUB

← 1 2 3 4 →