Aryl[a]pyrrolo[3,4-c]carbazoles as selective cyclin D1-CDK4 inhibitors

被引：54

作者：

Sanchez-Martinez, C

Shih, C

Faul, MM

Zhu, GX

Paal, M

Somoza, C

Li, TC

Kumrich, CA

Winneroski, LL

Xun, Z

Brooks, HB

Patel, BKR

Schultz, RM

DeHahn, TB

Spencer, CD

Watkins, SA

Considine, E

Dempsey, JA

Ogg, CA

Campbell, RM

Anderson, BA

Wagner, J

机构：

[1] Lilly Spain SA, DCR&T, Alcobendas 28108, Spain

[2] Eli Lilly & Co, Lilly Res Labs, DCR&T, Indianapolis, IN 46285 USA

[3] Lilly Forsch GmbH, DCR&T, D-20253 Hamburg, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 21期

关键词：

D O I：

10.1016/S0960-894X(03)00791-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis of new analogues of Arcyriaflavin A in which one indole ring is replaced by an aryl or heteroaryl ring is described. These new series of aryl[a]pyrrolo[3,4-c]carbazoles were evaluated as inhibitors of Cyclin D1-CDK4. A potent and selective D1-CDK4 inhibitor, 7a (D1-CDK4 IC50=45 nM), has been identified. The potency, selectivity profile against other kinases, and structure-activity relationship (SAR) trends of this class of compounds are discussed. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：3835 / 3839

页数：5

共 41 条

[1] Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases [J].

Barvian, M ;

Boschelli, DH ;

Cossrow, J ;

Dobrusin, E ;

Fattaey, A ;

Fritsch, A ;

Fry, D ;

Harvey, P ;

Keller, P ;

Garrett, M ;

La, F ;

Leopold, W ;

McNamara, D ;

Quin, M ;

Trumpp-Kallmeyer, S ;

Toogood, P ;

Wu, ZP ;

Zhang, EL .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (24) :4606-4616

[2] Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): Design, synthesis, enzymatic activities, and X-ray crystallographic analysis [J].

Bramson, HN ;

Corona, J ;

Davis, ST ;

Dickerson, SH ;

Edelstein, M ;

Frye, SV ;

Gampe, RT ;

Harris, PA ;

Hassell, A ;

Holmes, WD ;

Hunter, RN ;

Lackey, KE ;

Lovejoy, B ;

Luzzio, MJ ;

Montana, V ;

Rocque, WJ ;

Rusnak, D ;

Shewchuk, L ;

Veal, JM ;

Walker, DH ;

Kuyper, LF .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (25) :4339-4358

[3] Inhibition of cyclin-dependent kinase 2 by p21 is necessary for retinoblastoma protein-mediated G1 arrest after γ-irradiation [J].

Brugarolas, J ;

Moberg, K ;

Boyd, SD ;

Taya, Y ;

Jacks, T ;

Lees, JA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (03) :1002-1007

[4] Identification of selective inhibitors of cyclin dependent kinase 4 [J].

Carini, DJ ;

Kaltenbach, RF ;

Liu, J ;

Benfield, PA ;

Boylan, J ;

Boisclair, M ;

Brizuela, L ;

Burton, CR ;

Cox, S ;

Grafstrom, R ;

Harrison, BA ;

Harrison, K ;

Akamike, E ;

Markwalder, JA ;

Nakano, Y ;

Seitz, SP ;

Sharp, DM ;

Trainor, GL ;

Sielecki, TM .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (16) :2209-2211

[5] Synthesis and application of functionally diverse 2,6,9-trisubstituted purine libraries as CDK inhibitors [J].

Chang, YT ;

Gray, NS ;

Rosania, GR ;

Sutherlin, DP ;

Kwon, S ;

Norman, TC ;

Sarohia, R ;

Leost, M ;

Meijer, L ;

Schultz, PG .

CHEMISTRY & BIOLOGY, 1999, 6 (06) :361-375

[6]

DARZYNKIEWICZ Z, 1997, CURRENT PROTOCOLS CY

[7] Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase [J].

deAzevedo, WF ;

MuellerDieckmann, HJ ;

SchulzeGahmen, U ;

Worland, PJ ;

Sausville, E ;

Kim, SH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (07) :2735-2740

[8] 3D-QSAR CoMFA on cyclin-dependent kinase inhibitors [J].

Ducrot, P ;

Legraverend, M ;

Grierson, DS .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (22) :4098-4108

[9] A new one step synthesis of maleimides by condensation of glyoxylate esters with acetamides [J].

Faul, MM ;

Winneroski, LL ;

Krumrich, CA .

TETRAHEDRON LETTERS, 1999, 40 (06) :1109-1112

[10] A new, efficient method for the synthesis of bisindolylmaleimides [J].

Faul, MM ;

Winneroski, LL ;

Krumrich, CA .

JOURNAL OF ORGANIC CHEMISTRY, 1998, 63 (17) :6053-6058

← 1 2 3 4 5 →