Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors

被引：49

作者：

Burmistrov, Vladimir ^{[2
,3
]}

Morisseau, Christophe ^{[1
]}

Lee, Kin Sing Stephen ^{[1
]}

Shihadih, Diyala S. ^{[1
]}

Harris, Todd R. ^{[1
]}

Butov, Gennady M. ^{[2
,3
]}

Hammock, Bruce D. ^{[1
]}

机构：

[1] Univ Calif Davis, Ctr Comprehens Canc, Dept Entomol & Nematol, Davis, CA 95616 USA

[2] Volgograd State Tech Univ, Volzhsky Polytech Inst Branch, Dept Chem & Gen Chem Technol, Volzhsky, Russia

[3] Volgograd State Tech Univ, Volgograd, Russia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 09期

基金：

俄罗斯基础研究基金会;

关键词：

Soluble epoxide hydrolase; Inhibitor; Adamantane; Isocyanate; Diurea; EPOXYEICOSATRIENOIC ACIDS; WATER SOLUBILITY; BLOOD-PRESSURE; UREA; HYPERTENSION; HYDROLYSIS; MECHANISM; DISCOVERY;

D O I：

10.1016/j.bmcl.2014.03.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of inhibitors of the soluble epoxide hydrolase (sEH) containing two urea groups has been developed. Inhibition potency of the described compounds ranges from 2.0 mu M to 0.4 nM. 1,6-(Hexamethylene)bis[(adamant-1-yl) urea] (3b) was found to be a potent slow tight binding inhibitor (IC50 = 0.5 nM) with a strong binding to sEH (K-i = 3.1 nM) and a moderately long residence time on the enzyme (k(off) = 1.05 x 10(-3) s(-1); t(1/2) = 11 min). (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：2193 / 2197

页数：5

共 29 条

[11] Discovery of 2,8-diazaspiro[4.5]decane-based trisubstituted urea derivatives as highly potent soluble epoxide hydrolase inhibitors and orally active drug candidates for treating hypertension [J].

Kato, Yuko ;

Fuchi, Nobuhiro ;

Saburi, Hajime ;

Nishimura, Yutaka ;

Watanabe, Ayano ;

Yagi, Mai ;

Nakadera, Yasuhito ;

Higashi, Eriko ;

Yamada, Masateru ;

Aoki, Takumi .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (21) :5975-5979

[12] Optimization of amide-based inhibitors of soluble epoxide hydrolase with improved water solubility [J].

Kim, IH ;

Heirtzler, FR ;

Morisseau, C ;

Nishi, K ;

Tsai, HJ ;

Hammock, BD .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (10) :3621-3629

[13] Design, synthesis, and biological activity of 1,3-Disubstituted ureas as potent inhibitors of the soluble epoxide hydrolase of increased water solubility [J].

Kim, IH ;

Morisseau, C ;

Watanabe, T ;

Hammock, BD .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (08) :2110-2122

[14] Rapid synthesis of an array of trisubstituted urea-based soluble epoxide hydrolase inhibitors facilitated by a novel solid-phase method [J].

Kowalski, Jennifer A. ;

Swinamer, Alan D. ;

Muegge, Ingo ;

Eldrup, Anne B. ;

Kukulka, Alison ;

Cywin, Charles L. ;

De Lombaert, Stephane .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (12) :3703-3707

[15] Forster resonance energy transfer competitive displacement assay for human soluble epoxide hydrolase [J].

Lee, Kin Sing Stephen ;

Morisseau, Christophe ;

Yang, Jun ;

Wang, Peng ;

Hwang, Sung Hee ;

Hammock, Bruce D. .

ANALYTICAL BIOCHEMISTRY, 2013, 434 (02) :259-268

[16] Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings (Reprinted from Advanced Drug Delivery Reviews, vol 23, pg 3-25, 1997) [J].

Lipinski, CA ;

Lombardo, F ;

Dominy, BW ;

Feeney, PJ .

ADVANCED DRUG DELIVERY REVIEWS, 2001, 46 (1-3) :3-26

[17] QSAR and classification of murine and human soluble epoxide hydrolase inhibition by urea-like compounds [J].

McElroy, NR ;

Jurs, PC ;

Morisseau, C ;

Hammock, BD .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (06) :1066-1080

[18] A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening [J].

McGovern, SL ;

Caselli, E ;

Grigorieff, N ;

Shoichet, BK .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (08) :1712-1722

[19] Potent urea and carbamate inhibitors of soluble epoxide hydrolases [J].

Morisseau, C ;

Goodrow, MH ;

Dowdy, D ;

Zheng, J ;

Greene, JF ;

Sanborn, JR ;

Hammock, BD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (16) :8849-8854

[20] Structural refinement of inhibitors of urea-based soluble epoxide hydrolases [J].

Morisseau, C ;

Goodrow, MH ;

Newman, JW ;

Wheelock, CE ;

Dowdy, DL ;

Hammock, BD .

BIOCHEMICAL PHARMACOLOGY, 2002, 63 (09) :1599-1608

← 1 2 3 →