Discovery of indenopyrazoles as EGFR and VEGFR-2 tyrosine kinase inhibitors by in silico high-throughput screening

被引：46

作者：

Usui, Taikou ^{[1
]}

Ban, Hyun Seung ^{[1
]}

Kawada, Junpei ^{[1
]}

Hirokawa, Takatsugu ^{[2
]}

Nakamura, Hiroyuki ^{[1
]}

机构：

[1] Gakushuin Univ, Fac Sci, Dept Chem, Tokyo 1718588, Japan

[2] Inst Adv Ind Sci & Technol AIST, Computat Biol Res Ctr, Tokyo 1350064, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 01期

关键词：

D O I：

10.1016/j.bmcl.2007.10.084

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of indenopyrazoles 8 and 9 were designed and synthesized as EGFR tyrosine kinase inhibitors by in silico high-throughput screening. Compounds 8b and 8d showed significant inhibition of A431 cell growth (GI(50) = 0.062 and 0.057 mu M, respectively). Compounds 8b and 9a showed inhibitory activity toward both EGFR and VEGFR-2 (KDR) tyrosine kinases, whereas 8d inhibited VEGFR-2 tyrosine kinase, exclusively. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：285 / 288

页数：4

共 27 条

[1] GROWTH-FACTORS AND CANCER
AARONSON, SA
[J]. SCIENCE, 1991, 254 (5035) : 1146 - 1153
[2] DESIGN OF ENZYME-INHIBITORS USING ITERATIVE PROTEIN CRYSTALLOGRAPHIC ANALYSIS
APPELT, K
BACQUET, RJ
BARTLETT, CA
BOOTH, CLJ
FREER, ST
FUHRY, MAM
GEHRING, MR
HERRMANN, SM
HOWLAND, EF
JANSON, CA
JONES, TR
KAN, CC
KATHARDEKAR, V
LEWIS, KK
MARZONI, GP
MATTHEWS, DA
MOHR, C
MOOMAW, EW
MORSE, CA
OATLEY, SJ
OGDEN, RC
REDDY, MR
REICH, SH
SCHOETTLIN, WS
SMITH, WW
VARNEY, MD
VILLAFRANCA, JE
WARD, RW
WEBBER, S
WEBBER, SE
WELSH, KM
WHITE, J
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (07) : 1925 - 1934
[3] Benzamides and benzamidines as specific inhibitors of epidermal growth factor receptor and v-Src protein tyrosine kinases
Asano, T
Yoshikawa, T
Usui, T
Yamamoto, H
Yamamoto, Y
Uehara, Y
Nakamura, H
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (13) : 3529 - 3542
[4] Barbacci EG, 2003, CANCER RES, V63, P4450
[5] Erlotinib: a new therapeutic approach for non-small cell lung cancer
Bonomi, P
[J]. EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2003, 12 (08) : 1395 - 1401
[6] Chemical inhibitors of protein kinases
Bridges, AJ
[J]. CHEMICAL REVIEWS, 2001, 101 (08) : 2541 - 2571
[7] Streamlining lead discovery by aligning in silico and high-throughput screening
Davies, John W.
Glick, Meir
Jenkins, Jeremy L.
[J]. CURRENT OPINION IN CHEMICAL BIOLOGY, 2006, 10 (04) : 343 - 351
[8] OVEREXPRESSION OF TRANSFORMING GROWTH FACTOR-ALPHA IN PSORIATIC EPIDERMIS
ELDER, JT
FISHER, GJ
LINDQUIST, PB
BENNETT, GL
PITTELKOW, MR
COFFEY, RJ
ELLINGSWORTH, L
DERYNCK, R
VOORHEES, JJ
[J]. SCIENCE, 1989, 243 (4892) : 811 - 814
[9] Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy
Friesner, RA
Banks, JL
Murphy, RB
Halgren, TA
Klicic, JJ
Mainz, DT
Repasky, MP
Knoll, EH
Shelley, M
Perry, JK
Shaw, DE
Francis, P
Shenkin, PS
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (07) : 1739 - 1749
[10] Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer
Fukuoka, M
Yano, S
Giaccone, G
Tamura, T
Nakagawa, K
Douillard, JY
Nishiwaki, Y
Vansteenkiste, J
Kudoh, S
Rischin, D
Eek, R
Horai, T
Noda, K
Takata, I
Smit, E
Averbuch, S
Macleod, A
Feyereislova, A
Dong, RP
Baselga, J
[J]. JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (12) : 2237 - 2246

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