A novel dicyanotriterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile, active at picomolar concentrations for inhibition of nitric oxide production

被引：158

作者：

Honda, T

Honda, Y

Favaloro, FG

Gribble, GW ^{[1
]}

Suh, N

Place, AE

Rendi, MH

Sporn, MB

机构：

[1] Dartmouth Coll, Sch Med, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA

[2] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 07期

关键词：

D O I：

10.1016/S0960-894X(02)00105-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

New oleanane triterpenoids with various substituents at the C-17 position of 2-evano-3,12-dioxooleana-1,9(11)dien-28-oic acid (CDDO) and methyl 2-carboxy-3,12-dioxooleana-1,9(11)-dien-28-oate were synthesized. Among them, 2-cyano-3,12-dioxooleana- 1,9(11)-dien-28-onitrile shows extremely high inhibitory activity (IC50 = 1 pM level) against production of nitric oxide induced by interferon-gamma in mouse macrophages. This potency is about 100 times and 30 times more potent than CDDO and dexamethasone, respectively. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

收藏

页码：1027 / 1030

页数：4

相关论文

共 17 条

[1]

GLYCOSYLATION OF ACIDS UNDER PHASE-TRANSFER CONDITIONS - PARTIAL SYNTHESIS OF SAPONINS [J].

BLIARD, C ;

MASSIOT, G ;

NAZABADIOKO, S .

TETRAHEDRON LETTERS, 1994, 35 (33) :6107-6108

[2]

BOGDAN C, 1992, J BIOL CHEM, V267, P23301

[3]

HALOGENOLYSIS OF METHYL GLYCYRRHETATE WITH LITHIUM IODIDE-DIMETHYLFORMAMIDE [J].

DEAN, PDG .

JOURNAL OF THE CHEMICAL SOCIETY, 1965, (NOV) :6655-&

[4]

DING A, 1990, J IMMUNOL, V145, P940

[5]

AMINOALKOHOLE .3. NOR-OLEA-12-ENOL-17-AMIN UND OLEA-12-ENOL-28-AMIN [J].

DREFAHL, G ;

HUNECK, S .

CHEMISCHE BERICHTE-RECUEIL, 1958, 91 (02) :278-281

[6]

CHELATION AS A DRIVING FORCE IN ORGANIC REACTIONS .4 SYNTHESIS OF ALPHA-NITRO ACIDS BY CONTROL OF CARBOXYLATION-DECARBOXYLATION EQUILIBRIUM [J].

FINKBEINER, HL ;

STILES, M .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1963, 85 (05) :616-&

[7]

ALLYL ESTERS AS CARBOXY PROTECTING GROUPS IN THE SYNTHESIS OF O-GLYCOPEPTIDES [J].

FRIEDRICHBOCHNITSCHEK, S ;

WALDMANN, H ;

KUNZ, H .

JOURNAL OF ORGANIC CHEMISTRY, 1989, 54 (04) :751-756

[8]

Design and synthesis of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, a novel and highly active inhibitor of nitric oxide production in mouse macrophages [J].

Honda, T ;

Rounds, BV ;

Gribble, GW ;

Suh, NJ ;

Wang, YP ;

Sporn, MB .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (19) :2711-2714

[9]

Novel synthetic oleanane triterpenoids: A series of highly active inhibitors of nitric oxide production in mouse macrophages [J].

Honda, T ;

Rounds, BV ;

Bore, L ;

Favaloro, FG ;

Gribble, GW ;

Suh, N ;

Wang, YP ;

Sporn, MB .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (24) :3429-3434

[10]

Synthetic oleanane and ursane triterpenoids with modified rings A and C: A series of highly active inhibitors of nitric oxide production in mouse macrophages [J].

Honda, T ;

Rounds, BV ;

Bore, L ;

Finlay, HJ ;

Favaloro, FG ;

Suh, N ;

Wang, YP ;

Sporn, MB ;

Gribble, GW .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (22) :4233-4246