ANTIVIRAL AND ANTITUMOR STRUCTURE ACTIVITY RELATIONSHIP STUDIES ON TETRACYCLIC EUDISTOMINS

被引：31

作者：

VANMAARSEVEEN, JH

HERMKENS, PHH

DECLERCQ, E

BALZARINI, J

SCHEEREN, HW

KRUSE, CG

机构：

[1] SOLVAY DUPHAR RES LABS,POB 900,1380 DA WEESP,NETHERLANDS

[2] CATHOLIC UNIV NIJMEGEN,DEPT ORGAN CHEM,6525 ED NIJMEGEN,NETHERLANDS

[3] CATHOLIC UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 17期

关键词：

D O I：

10.1021/jm00095a019

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The in vitro antiviral and antitumor activities of (-)-debromoeudistomin K (1a) and 10 structural analogues (1b-1j and 11) were evaluated. The synthesis was accomplished with an intramolecular Pictet-Spengler condensation reaction as the key step. This examination revealed some structural and stereochemical features that are important for both the antiviral and antitumor activities. The most striking points for activity are the necessity to have the correct natural stereochemistry at both C(1) and C(13b) and the presence of the C(1)-NH2 substituent. As was revealed before with naturally isolated eudistomins a substituent in the indole ring greatly influences the biological activity. The 5-OMe derivative Ih shows high potency in both antiviral and antitumor models.

引用

页码：3223 / 3230

页数：8

共 23 条

[1] MARKED INVIVO ANTIRETROVIRUS ACTIVITY OF 9-(2-PHOSPHONYLMETHOXY-ETHYL)ADENINE, A SELECTIVE ANTI-HUMAN IMMUNODEFICIENCY VIRUS AGENT
BALZARINI, J
NAESENS, L
HERDEWIJN, P
ROSENBERG, I
HOLY, A
PAUWELS, R
BABA, M
JOHNS, DG
DECLERCQ, E
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (01) : 332 - 336
[2] ROLE OF THYMIDINE KINASE IN THE INHIBITORY ACTIVITY OF 5-SUBSTITUTED-2'-DEOXYURIDINES ON THE GROWTH OF HUMAN AND MURINE TUMOR-CELL LINES
BALZARINI, J
DECLERCQ, E
TORRENCE, PF
MERTES, MP
PARK, JS
SCHMIDT, CL
SHUGAR, D
BARR, PJ
JONES, AS
VERHELST, G
WALKER, RT
[J]. BIOCHEMICAL PHARMACOLOGY, 1982, 31 (06) : 1089 - 1095
[3] MARINE PRODUCTS AS A SOURCE OF ANTIVIRAL DRUG LEADS
CHE, CT
[J]. DRUG DEVELOPMENT RESEARCH, 1991, 23 (03) : 201 - 218
[4] COMPARATIVE EFFICACY OF ANTIHERPES DRUGS AGAINST DIFFERENT STRAINS OF HERPES-SIMPLEX VIRUS
DECLERCQ, E
DESCAMPS, J
VERHELST, G
WALKER, RT
JONES, AS
TORRENCE, PF
SHUGAR, D
[J]. JOURNAL OF INFECTIOUS DISEASES, 1980, 141 (05) : 563 - 574
[5] BROAD-SPECTRUM ANTIVIRAL ACTIVITY OF THE CARBOCYCLIC ANALOG OF 3-DEAZAADENOSINE
DECLERCQ, E
MONTGOMERY, JA
[J]. ANTIVIRAL RESEARCH, 1983, 3 (01) : 17 - 24
[6] BROAD-SPECTRUM ANTIVIRAL AND CYTOCIDAL ACTIVITY OF CYCLOPENTENYLCYTOSINE, A CARBOCYCLIC NUCLEOSIDE TARGETED AT CTP SYNTHETASE
DECLERCQ, E
MURASE, J
MARQUEZ, VE
[J]. BIOCHEMICAL PHARMACOLOGY, 1991, 41 (12) : 1821 - 1829
[7] DECLERCQ E, 1981, MOL PHARMACOL, V19, P321
[8] CRYSTAL-STRUCTURE DETERMINATION OF (1S,13BR)-1-AMINO-10-METHOXY-1,2,7,8,13,13B-HEXAHYDRO-[1,6,2]OXATHIAZEPINO[2',3'-1,2]PYRIDO[3,4-B]INDOLE MONOHYDRATE, C15H19N3O2S.H2O
HERMKENS, PHH
VONMAARSEVEEN, JH
BOSMAN, WP
SMITS, JMM
BEURSKENS, PT
[J]. JOURNAL OF CRYSTALLOGRAPHIC AND SPECTROSCOPIC RESEARCH, 1990, 20 (03): : 313 - 317
[9] INTRAMOLECULAR PICTET-SPENGLER REACTION OF N-ALKOXYTRYPTOPHANS AND TRYPTAMINES .2. SYNTHESIS OF CORYNANTHE ALKALOID DERIVATIVES CONTAINING A TETRAHYDRO-1,2-OXAZINE AS THE D-RING
HERMKENS, PHH
VONMAARSEVEEN, JH
BERENS, HW
SMITS, JMM
KRUSE, CG
SCHEEREN, HW
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (07) : 2200 - 2206
[10] INTRAMOLECULAR PICTET-SPENGLER REACTION OF N-ALKOXYTRYPTAMINES .3. STEREOSELECTIVE SYNTHESIS OF (-)-DEBROMOEUDISTOMIN-L AND (-)-O-METHYLDEBROMOEUDISTOMIN-E AND THEIR STEREOISOMERS
HERMKENS, PHH
VONMAARSEVEEN, JH
OTTENHEIJM, HCJ
KRUSE, CG
SCHEEREN, HW
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (13) : 3998 - 4006

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