EB1627:: a soluble prodrug of the potent anticancer cyanoguanidine CHS828

被引：48

作者：

Binderup, E

Björkling, F

Hjarnaa, PV

Latini, S

Baltzer, B

Carlsen, M

Binderup, L

机构：

[1] LEO Pharma, Dept Med Chem, DK-2750 Ballerup, Denmark

[2] LEO Pharma, Dept Pharmacol, DK-2750 Ballerup, Denmark

[3] LEO Pharma, Dept Biochem, DK-2750 Ballerup, Denmark

[4] LEO Pharma, Dept Spect, DK-2750 Ballerup, Denmark

[5] LEO Pharma, Dept Metab & Pharmacokinet, DK-2750 Ballerup, Denmark

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 10期

关键词：

anticancer cyanoguanidine; prodrug; EB1627;

D O I：

10.1016/j.bmcl.2005.03.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To overcome pharmacokinetic and solubility problems observed in early clinical trials with the potent anticancer compound CHS828, we synthesised a series of prodrugs with improved properties. The best compound obtained was EB1627, with a tetraethyleneglycol moiety attached to the parent drug via a carbonate linkage. This compound was found soluble enough to be given i.v. and the drug was rapidly released in vivo exerting a very potent inhibitory activity alone and in combination with known cytostatics (etoposide) in animal models in vivo. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：2491 / 2494

页数：4

共 9 条

[1] BARCELO G, 1986, SYNTHESIS-STUTTGART, P627
[2] CHLOROSULFATES AS REAGENTS IN THE SYNTHESIS OF CARBOXYLIC-ACID ESTERS UNDER PHASE-TRANSFER CONDITIONS
BINDERUP, E
HANSEN, ET
[J]. SYNTHETIC COMMUNICATIONS, 1984, 14 (09) : 857 - 864
[3] Bodor N, 2000, MED RES REV, V20, P58, DOI 10.1002/(SICI)1098-1128(200001)20:1<58::AID-MED3>3.0.CO
[4] 2-X
[5] Drug delivery systems: Water soluble taxol 2'-poly(ethylene glycol) ester prodrugs - Design and in vivo effectiveness
Greenwald, RB
Gilbert, CW
Pendri, A
Conover, CD
Xia, J
Martinez, A
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (02) : 424 - 431
[6] Hjarnaa PJV, 1999, CANCER RES, V59, P5751
[7] Hovstadius P, 2002, CLIN CANCER RES, V8, P2843
[8] Anticancer agent CHS 828 suppresses nuclear factor-κB activity in cancer cells through downregulation of ikk activity
Olsen, LS
Hjarnaa, PJV
Latini, S
Holm, PK
Larsson, R
Bramm, E
Binderup, L
Madsen, MW
[J]. INTERNATIONAL JOURNAL OF CANCER, 2004, 111 (02) : 198 - 205
[9] Novel cyanoguanidines with potent oral antitumour activity
Schou, C
Ottosen, ER
Petersen, HJ
Björkling, F
Latini, S
Hjarnaa, PV
Bramm, E
Binderup, L
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (24) : 3095 - 3100

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