SYNTHESIS OF 2-O-HETEROAROYL TAXANES - EVALUATION OF MICROTUBULE ASSEMBLY PROMOTION AND CYTOTOXICITY

被引：12

作者：

GEORG, GI ^{[1
]}

HARRIMAN, GCB ^{[1
]}

ALI, SM ^{[1
]}

DATTA, A ^{[1
]}

HEPPERLE, M ^{[1
]}

HIMES, RH ^{[1
]}

机构：

[1] UNIV KANSAS,DEPT BIOCHEM,LAWRENCE,KS 66045

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1995年 / 5卷 / 02期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/0960-894X(94)00468-U

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of heterocyclic taxanes were synthesized and evaluated to investigate structure activity relationships at the 2-position of paclitaxel. The compounds were prepared through a regioselective deacylation, reacylation sequence of suitably protected paclitaxel. The heterocyclic substituted diterpenes were synthesized from paclitaxel in four steps in high overall yields. Evaluation of these analogues in a microtubule assembly assay and for their cytotoxicity against B16 melanoma cells illustrated that these compounds had diminished activity compared to paclitaxel.

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收藏

页码：115 / 118

页数：4

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共 26 条

[1] THE EFFECT OF THE AROMATIC RINGS OF TAXOL ON BIOLOGICAL-ACTIVITY AND SOLUTION CONFORMATION - SYNTHESIS AND EVALUATION OF SATURATED TAXOL AND TAXOTERE ANALOGS [J].

BOGE, TC ;

HIMES, RH ;

VANDERVELDE, DG ;

GEORG, GI .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (20) :3337-3343

[2] UNEXPECTEDLY FACILE HYDROLYSIS OF THE 2-BENZOATE GROUP OF TAXOL AND SYNTHESES OF ANALOGS WITH INCREASED ACTIVITIES [J].

CHAUDHARY, AG ;

GHARPURE, MM ;

RIMOLDI, JM ;

CHORDIA, MD ;

GUNATILAKA, AAL ;

KINGSTON, DGI ;

GROVER, S ;

LIN, CM ;

HAMEL, E .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1994, 116 (09) :4097-4098

[3] STRUCTURE-ACTIVITY-RELATIONSHIPS OF TAXOL(R) - SYNTHESIS AND BIOLOGICAL EVALUATION OF C2 TAXOL ANALOGS [J].

CHEN, SH ;

FARINA, V ;

WEI, JM ;

LONG, B ;

FAIRCHILD, C ;

MAMBER, SW ;

KADOW, JF ;

VYAS, D ;

DOYLE, TW .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (03) :479-482

[4] 4-DEACETYLTAXOL AND 10-ACETYL-4-DEACETYLTAXOTERE - SYNTHESIS AND BIOLOGICAL EVALUATION [J].

DATTA, A ;

JAYASINGHE, LR ;

GEORG, GI .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (24) :4258-4260

[5] THE FIRST-SYNTHESIS OF A C-9 CARBONYL MODIFIED BACCATIN-III DERIVATIVE AND ITS CONVERSION TO NOVEL TAXOL(R) AND TAXOTERE(R) ANALOGS [J].

DATTA, A ;

AUBE, J ;

GEORG, GI ;

MITSCHER, LA ;

JAYASINGHE, LR .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (15) :1831-1834

[6] INTERNAL NUCLEOPHILE ASSISTED SELECTIVE DEESTERIFICATION STUDIES ON BACCATIN-III - SYNTHESIS OF 2-DEBENZOYLBACCATIN-III AND 4-DEACETYLBACCATIN-III ANALOGS [J].

DATTA, A ;

JAYASINGHE, LR ;

GEORG, GI .

JOURNAL OF ORGANIC CHEMISTRY, 1994, 59 (16) :4689-4690

[7] SYNTHESIS OF BIOLOGICALLY-ACTIVE TAXOL ANALOGS WITH MODIFIED PHENYLISOSERINE SIDE-CHAINS [J].

GEORG, GI ;

CHERUVALLATH, ZS ;

HIMES, RH ;

MEJILLANO, MR ;

BURKE, CT .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (22) :4230-4237

[8] SYNTHESIS AND BIOLOGY OF SUBSTITUTED 3'-PHENYL TAXOL ANALOGS [J].

GEORG, GI ;

CHERUVALLATH, ZS ;

HARRIMAN, GCB ;

HEPPERLE, M ;

PARK, H ;

HIMES, RH .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (19) :2331-2336

[9] TOPLISS APPROACH TO THE SYNTHESIS OF BIOLOGICALLY-ACTIVE SUBSTITUTED N-BENZOYL TAXOL ANALOGS [J].

GEORG, GI ;

BOGE, TC ;

CHERUVALLATH, ZS ;

HARRIMAN, GCB ;

HEPPERLE, M ;

PARK, H ;

HIMES, RH .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (15) :1825-1830

[10] NOVEL BIOLOGICALLY-ACTIVE TAXOL ANALOGS - BACCATIN-III 13-(N-(PARA-CHLOROBENZOYL)-(2'R,3'S)-3'-PHENYLISOSERINATE) AND BACCATIN-III 13-(N-BENZOYL-(2'R,3'S)-3'-(PARA-CHLOROPHENYL)ISOSERINATE) [J].

GEORG, GI ;

CHERUVALLATH, ZS ;

HIMES, RH ;

MEJILLANO, MR .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1992, 2 (04) :295-298