Synthesis and structure-activity relationships of novel 2',2'-difluoro analogues of docetaxel

被引：0

作者：

Uoto, K ^{[1
]}

Ohsuki, S ^{[1
]}

Takenoshita, H ^{[1
]}

Ishiyama, T ^{[1
]}

Iimura, S ^{[1
]}

Hirota, Y ^{[1
]}

Mitsui, I ^{[1
]}

Terasawa, H ^{[1
]}

Soga, T ^{[1
]}

机构：

[1] DAIICHI PHARMACEUT CO LTD, NEW PROD RES LABS 4, EDOGAWA KU, TOKYO 134, JAPAN

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 1997年 / 45卷 / 11期

关键词：

docetaxel; paclitaxel; 2'; 2'-difluoro analogue; structure-activity relationship; cytotoxicity; microtubule disassembly-inhibitory activity;

D O I：

暂无

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To investigate the role of the 2'-hydroxy group at the C-13 side chain of docetaxel in the antitumor activity, we prepared several 2',2'-difluoro derivatives of docetaxel and evaluated their cytotoxicity against mouse leukemia and human tumor cell lines and their microtubule disassembly-inhibitory activity. These analogues were prepared by esterification of protected 10-deacetylbaccatin III (21) with appropriate alpha,alpha-difluorinated carboxylic acids (Charts 1 and 2). Among these 2',2'-difluorodocetaxel derivatives, 2',2'-difluorodocetaxel (23b) was approximately 3-10 times as active as 2'-fluorodocetaxel (29a) in terms of cytotoxicity. In addition, the 3'-(2-furyl) (23h) and 3'-(2-pyrrolyl) (23p) analogues showed activity comparable or superior to that of docetaxel (2).

引用

页码：1793 / 1804

页数：12

共 35 条

[1]

ALLEY MC, 1988, CANCER RES, V48, P589

[2] A PRACTICAL ACCESS TO CHIRAL PHENYLISOSERINATES, PREPARATION OF TAXOTERE(R) ANALOGS [J].

BOURZAT, JD ;

COMMERCON, A .

TETRAHEDRON LETTERS, 1993, 34 (38) :6049-6052

[3] PREPARATION OF ALPHA,ALPHA-DIFLUORO-BETA-HYDROXY ESTERS VIA A MODIFIED REFORMATSKY REACTION [J].

CURRAN, TT .

JOURNAL OF ORGANIC CHEMISTRY, 1993, 58 (23) :6360-6363

[4] A HIGHLY EFFICIENT, PRACTICAL APPROACH TO NATURAL TAXOL [J].

DENIS, JN ;

GREENE, AE ;

GUENARD, D ;

GUERITTEVOEGELEIN, F ;

MANGATAL, L ;

POTIER, P .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1988, 110 (17) :5917-5919

[5] CHARACTERIZATION OF TAXOL IN METHYLENE-CHLORIDE BY NMR-SPECTROSCOPY [J].

FALZONE, CJ ;

BENESI, AJ ;

LECOMTE, JTJ .

TETRAHEDRON LETTERS, 1992, 33 (09) :1169-1172

[6] TURBIDIMETRIC STUDIES OF INVITRO ASSEMBLY AND DISASSEMBLY OF PORCINE NEUROTUBULES [J].

GASKIN, F ;

CANTOR, CR ;

SHELANSKI, ML .

JOURNAL OF MOLECULAR BIOLOGY, 1974, 89 (04) :737-+

[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] 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

[9] HETEROAROMATIC TAXOL ANALOGS - THE CHEMISTRY AND BIOLOGICAL-ACTIVITIES OF 3'-FURYL AND 3'-PYRIDYL SUBSTITUTED TAXANES [J].

GEORG, GI ;

HARRIMAN, GCB ;

HEPPERLE, M ;

HIMES, RH .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (11) :1381-1384

[10]

GEORG GI, 1992, BIOORG MED CHEM LETT, V2, P1751

← 1 2 3 4 →