RIGID ANALOGS OF CAMPTOTHECIN AS DNA TOPOISOMERASE-I INHIBITORS

被引：37

作者：

LACKEY, K ^{[1
]}

BESTERMAN, JM ^{[1
]}

FLETCHER, W ^{[1
]}

LEITNER, P ^{[1
]}

MORTON, B ^{[1
]}

STERNBACH, DD ^{[1
]}

机构：

[1] GLAXO RES INST,DEPT MOLEC BIOL,RES TRIANGLE PK,NC 27709

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 06期

关键词：

D O I：

10.1021/jm00006a008

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Substituted 8-ethyl-2-(2-oxo-1,2-dihydroindol-3-ylidene)-8-hydroxy-2,3,5,8-tetrahydro-6-oxa-3a-azacyclopenta[b]naphthalene-1,4,7-triones were synthesized and evaluated as topoisomerase I inhibitors in an in vitro cleavable complex assay. The activity of these compounds may be attributed to their rigid, planar geometry, and an attempt was made to correlate the SAR in this series to known attributes of camptothecin.

引用

页码：906 / 911

页数：6

共 25 条

[1] ETODOLIC ACID AND RELATED COMPOUNDS - CHEMISTRY AND ANTIINFLAMMATORY ACTIONS OF SOME POTENT DISUBSTITUTED AND TRISUBSTITUTED 1,3,4,9-TETRAHYDROPYRANO[3,4-B]INDOLE-1-ACETIC ACIDS [J].

DEMERSON, CA ;

HUMBER, LG ;

PHILIPP, AH ;

MARTEL, RR .

JOURNAL OF MEDICINAL CHEMISTRY, 1976, 19 (03) :391-395

[2] INHIBITORS OF DNA TOPOISOMERASE-I ISOLATED FROM THE ROOTS OF ZANTHOXYLUM-NITIDUM [J].

FANG, SD ;

WANG, LK ;

HECHT, SM .

JOURNAL OF ORGANIC CHEMISTRY, 1993, 58 (19) :5025-5027

[3] MECHANISM-BASED STUDIES OF NATURAL-PRODUCTS IN DRUG DISCOVERY - A STRATEGY FOR IDENTIFYING NOVEL, MECHANISTICALLY UNIQUE INHIBITORS OF TOPOISOMERASE-I [J].

HECHT, SM ;

BERRY, DE ;

MACKENZIE, LJ ;

BUSBY, RW ;

NASUTI, CA .

JOURNAL OF NATURAL PRODUCTS, 1992, 55 (04) :401-413

[4] MODIFICATION OF THE HYDROXY LACTONE RING OF CAMPTOTHECIN - INHIBITION OF MAMMALIAN TOPOISOMERASE-I AND BIOLOGICAL-ACTIVITY [J].

HERTZBERG, RP ;

CARANFA, MJ ;

HOLDEN, KG ;

JAKAS, DR ;

GALLAGHER, G ;

MATTERN, MR ;

MONG, SM ;

BARTUS, JO ;

JOHNSON, RK ;

KINGSBURY, WD .

JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (03) :715-720

[5]

HERTZBERG RP, 1991, DNA TOPOISOMERASES C, P103

[6]

HOLMES RE, 1836, Patent No. 427946

[7]

HSIANG YH, 1985, J BIOL CHEM, V260, P4873

[8]

HSIANG YH, 1989, CANCER RES, V49, P4385

[9] SYNTHESIS OF WATER-SOLUBLE (AMINOALKYL)CAMPTOTHECIN ANALOGS - INHIBITION OF TOPOISOMERASE-I AND ANTITUMOR-ACTIVITY [J].

KINGSBURY, WD ;

BOEHM, JC ;

JAKAS, DR ;

HOLDEN, KG ;

HECHT, SM ;

GALLAGHER, G ;

CARANFA, MJ ;

MCCABE, FL ;

FAUCETTE, LF ;

JOHNSON, RK ;

HERTZBERG, RP .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (01) :98-107

[10] SYNTHESIS OF C-NOR-4,6-SECOCAMPTOTHECIN AND RELATED-COMPOUNDS [J].

KURIHARA, T ;

TANNO, H ;

TAKEMURA, S ;

HARUSAWA, S ;

YONEDA, R .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1993, 30 (03) :643-652

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