Synthesis of 6-or 4-functionalized indoles via a reductive cyclization approach and evaluation as aromatase inhibitors

被引：36

作者：

Leze, Marie-Pierre ^{[1
]}

Palusczak, Anja ^{[2
]}

Hartmann, Rolf W. ^{[2
]}

Le Borgne, Marc ^{[1
]}

机构：

[1] Univ Nantes, Nantes Atlantique Univ, Dept Pharmacochim, IlCiMed,UPRES EA 1155,UFR Sci Pharmaceut, F-44035 Nantes 1, France

[2] Univ Saarland, Fachrichtung Pharmaceut & Med Chem, D-66041 Saarbrucken, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 16期

关键词：

breast cancer; aromatase inhibitors; indole; azoles; benzonitrile derivatives; reductive cyclization;

D O I：

10.1016/j.bmcl.2008.06.094

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two new series of benzonitrile derivatives on position 6 or 4 of indole ring were successfully synthesized via a Leimgruber-Batcho reaction. All the compounds were evaluated in vitro on the inhibition of aromatase (CYP19) and 17 alpha-hydroxylase-C17,20-lyase (CYP17). The racemate, 4-[(1H-imidazol-1-yl)(1H-indol-4-yl)methyl]benzonitrile 9, showed high level of inhibitory activity towards CYP19 (IC50 = 11.5 nM). (C) 2008 Elsevier Ltd. Ail rights reserved.

引用

页码：4713 / 4715

页数：3

共 22 条

[1] Fast microwave-assisted preparation of aryl and vinyl nitriles and the corresponding tetrazoles from organo-halides [J].

Alterman, M ;

Hallberg, A .

JOURNAL OF ORGANIC CHEMISTRY, 2000, 65 (23) :7984-7989

[2]

ASTOIN J, 1980, EUR J MED CHEM, V15, P457

[3]

CLARK RD, 1984, HETEROCYCLES, V22, P195

[4] STRUCTURE AND SYNTHESIS OF A NEW BROMOINDOLE FROM A MARINE SPONGE [J].

DELLAR, G ;

DJURA, P ;

SARGENT, MV .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1981, (06) :1679-1684

[5] Development of a simple and rapid assay for the evaluation of inhibitors of human 17α-hydroxylase-C17,21-lyase (P450c17) by coexpression of P450c17 with NADPH-cytochrome-P450-reductase in Escherichia coli [J].

Ehmer, PB ;

Jose, J ;

Hartmann, RW .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2000, 75 (01) :57-63

[6] STEREOSELECTIVE INHIBITION OF AROMATASE BY ENANTIOMERS OF AMINOGLUTETHIMIDE [J].

GRAVES, PE ;

SALHANICK, HA .

ENDOCRINOLOGY, 1979, 105 (01) :52-57

[7]

Hoffmann J, 2007, TOP MED CHEM SER, V1, P19, DOI 10.1007/7355_2006_002

[8] RAPID ESTERIFICATION BY MEANS OF MIXED ANHYDRIDE AND ITS APPLICATION TO LARGE-RING LACTONIZATION [J].

INANAGA, J ;

HIRATA, K ;

SAEKI, H ;

KATSUKI, T ;

YAMAGUCHI, M .

BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, 1979, 52 (07) :1989-1993

[9] Aromatase inhibitors for therapy of advanced breast cancer [J].

Ingle, JN ;

Suman, VJ .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2005, 95 (1-5) :113-119

[10] Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer [J].

Jordan, V. Craig ;

Brodie, Angela M. H. .

STEROIDS, 2007, 72 (01) :7-25

← 1 2 3 →