Identification of novel and improved antimitotic agents derived from noscapine

被引：59

作者：

Anderson, JT ^{[1
]}

Ting, AE ^{[1
]}

Boozer, S ^{[1
]}

Brunden, KR ^{[1
]}

Crumrine, C ^{[1
]}

Danzig, J ^{[1
]}

Dent, T ^{[1
]}

Faga, L ^{[1
]}

Harrington, JJ ^{[1
]}

Hodnick, WF ^{[1
]}

Murphy, SM ^{[1
]}

Pawlowski, G ^{[1
]}

Perry, R ^{[1
]}

Raber, A ^{[1
]}

Rundlett, SE ^{[1
]}

Stricker-Krongrad, A ^{[1
]}

Wang, JM ^{[1
]}

Bennani, YL ^{[1
]}

机构：

[1] Athersys Inc, Cleveland, OH 44115 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 23期

关键词：

D O I：

10.1021/jm050674q

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Analogues of the natural product noscapine were synthesized and their potential as antitumor agents evaluated. The discovery of a novel regioselective 0-demethylation facilitated the synthesis of the potent aniline 6, which arrests mammalian cells in the G2/M phase of the cell cycle at 0.1 mu M and also affects tubulin polymerization. Aniline 6 is orally bioavailable and is 250-fold more potent than noscapine in reducing cell proliferation in rapidly dividing cells.

引用

收藏

页码：7096 / 7098

页数：3

相关论文

共 26 条

[1] Discovery of S-phase arresting agents derived from noscapine [J].

Anderson, JT ;

Ting, AE ;

Boozer, S ;

Brunden, KR ;

Danzig, J ;

Dent, T ;

Harrington, JJ ;

Murphy, SM ;

Perry, R ;

Raber, A ;

Rundlett, SE ;

Wang, JM ;

Wang, N ;

Bennani, YL .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (08) :2756-2758

[2] PHARMACOKINETIC PROPERTIES OF NOSCAPINE [J].

DAHLSTROM, B ;

MELLSTRAND, T ;

LOFDAHL, CG ;

JOHANSSON, M .

EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1982, 22 (06) :535-539

[3]

Fleming S, 2001, Expert Opin Emerg Drugs, V6, P317, DOI 10.1517/14728214.6.2.317

[4] Room-temperature palladium-catalyzed amination of aryl bromides and chlorides and extended scope of aromatic C-N bond formation with a commercial ligand [J].

Hartwig, JF ;

Kawatsura, M ;

Hauck, SI ;

Shaughnessy, KH ;

Alcazar-Roman, LM .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (15) :5575-5580

[5] Microtubules as a target for anticancer drugs [J].

Jordan, MA ;

Wilson, L .

NATURE REVIEWS CANCER, 2004, 4 (04) :253-265

[6] Noscapine and analogues as potential chemotherapeutic agents [J].

Joshi, HC ;

Zhou, J .

DRUG NEWS & PERSPECTIVES, 2000, 13 (09) :543-546

[7] Noscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses [J].

Ke, Y ;

Ye, K ;

Grossniklaus, HE ;

Archer, DR ;

Joshi, HC ;

Kapp, JA .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2000, 49 (4-5) :217-225

[8] Aqueous hydroxide as a base for palladium-catalyzed amination of aryl chlorides and bromides [J].

Kuwano, R ;

Utsunomiya, M ;

Hartwig, JF .

JOURNAL OF ORGANIC CHEMISTRY, 2002, 67 (18) :6479-6486

[9]

Landen JW, 2002, CANCER RES, V62, P4109

[10] Palladium-catalyzed synthesis of arylamines from aryl halides and lithium bis(trimethylsilyl)amide as an ammonia equivalent [J].

Lee, S ;

Jorgensen, M ;

Hartwig, JF .

ORGANIC LETTERS, 2001, 3 (17) :2729-2732