STRUCTURE-ACTIVITY STUDIES OF ANTITUMOR TAXANES - SYNTHESIS OF NOVEL C-13 SIDE-CHAIN HOMOLOGATED TAXOL AND TAXOTERE ANALOGS

被引：34

作者：

JAYASINGHE, LR ^{[1
]}

DATTA, A ^{[1
]}

ALI, SM ^{[1
]}

ZYGMUNT, J ^{[1
]}

VANDERVELDE, DG ^{[1
]}

GEORG, GI ^{[1
]}

机构：

[1] UNIV KANSAS,DEPT MED CHEM,LAWRENCE,KS 66045

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 37卷 / 18期

关键词：

D O I：

10.1021/jm00044a020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Taxol and taxotere analogs with one carbon homologated side chains were synthesized from 10-deacetylbaccatin III and a key oxazolidineacetic acid intermediate, which was synthesized in four steps from (S)-(+)-2-phenylglycine. 10-Deacetyl-1a'-homotaxol and 1a'-homotaxotere were at least 27 times less active than taxol in the microtubule assembly assay. The inability of these homologs to induce microtubule formation may be due to unfavorable solution conformations, preventing productive interactions with the taxol binding site on microtubules.

引用

页码：2981 / 2984

页数：4

共 24 条

[1] BLECHERT S, 1990, ALKALOIDS CHEM PHARM, V39, P195
[2] PHASE-II STUDY OF TAXOL, MERBARONE, AND PIROXANTRONE IN STAGE-IV NON-SMALL-CELL LUNG-CANCER - THE EASTERN COOPERATIVE ONCOLOGY GROUP RESULTS
CHANG, AY
KIM, K
GLICK, J
ANDERSON, T
KARP, D
JOHNSON, D
[J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (05) : 388 - 394
[3] IMPROVED PROTECTION AND ESTERIFICATION OF A PRECURSOR OF THE TAXOTERE(R) AND TAXOL SIDE-CHAINS
COMMERCON, A
BEZARD, D
BERNARD, F
BOURZAT, JD
[J]. TETRAHEDRON LETTERS, 1992, 33 (36) : 5185 - 5188
[4] DIRECT, HIGHLY EFFICIENT SYNTHESIS FROM (S)-(+)-PHENYLGLYCINE OF THE TAXOL AND TAXOTERE SIDE-CHAINS
DENIS, JN
CORREA, A
GREENE, AE
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1991, 56 (24) : 6939 - 6942
[5] FORASTIERE AA, 1993, SEMIN ONCOL, V20, P56
[6] SYNTHESIS OF BIOLOGICALLY-ACTIVE TAXOL ANALOGS WITH MODIFIED PHENYLISOSERINE SIDE-CHAINS
GEORG, GI
CHERUVALLATH, ZS
HIMES, RH
MEJILLANO, MR
BURKE, CT
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (22) : 4230 - 4237
[7] SCHOTTEN-BAUMANN ACYLATION OF N-DEBENZOYLTAXOL - AN EFFICIENT ROUTE TO N-ACYL TAXOL ANALOGS AND THEIR BIOLOGICAL EVALUATION
GEORG, GI
BOGE, TC
CHERUVALLATH, ZS
HARRIMAN, GCB
HEPPERLE, M
PARK, H
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (02) : 335 - 338
[8] A REINVESTIGATION OF THE TAXOL CONTENT OF HIMALAYAN TAXUS-WALLICHIANA ZUCC AND A REVISION OF THE STRUCTURE OF BREVIFOLIOL
GEORG, GI
GOLLAPUDI, SR
GRUNEWALD, GL
GUNN, CW
HIMES, RH
RAO, BK
LIANG, XZ
MIRHOM, YW
MITSCHER, LA
VANDERVELDE, DG
YE, QM
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1993, 3 (06) : 1345 - 1348
[9] AN EFFICIENT SEMISYNTHESIS OF TAXOL FROM (3R,4S)-N-BENZOYL-3-[(T-BUTYLDIMETHYLSILYL)OXY]-4-PHENYL-2-AZETIDINONE AND 7-(TRIETHYLSILYL)BACCATIN III
GEORG, GI
CHERUVALLATH, ZS
HARRIMAN, GCB
HEPPERLE, M
PARK, H
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1993, 3 (11) : 2467 - 2470
[10] GEORG GI, 1994, EXPERT OPIN THER PAT, V4, P109

← 1 2 3 →