Design, synthesis, and characterization of novel, nonquaternary reactivators of GF-inhibited human acetylcholinesterase

被引：20

作者：

McHardy, Stanton F. ^{[1
]}

Bohmann, Jonathan A. ^{[1
]}

Corbett, Michael R. ^{[1
]}

Campos, Bismarck ^{[1
]}

Tidwell, Michael W. ^{[1
]}

Thompson, Paul Marty ^{[1
]}

Bemben, Chris J. ^{[1
]}

Menchaca, Tony A. ^{[1
]}

Reeves, Tony E. ^{[1
]}

Cantrell, William R., Jr. ^{[1
]}

Bauta, William E. ^{[1
]}

Lopez, Ambrosio ^{[1
]}

Maxwell, Donald M. ^{[2
]}

Brecht, Karen M. ^{[2
]}

Sweeney, Richard E. ^{[2
]}

McDonough, John ^{[2
]}

机构：

[1] SW Res Inst, Chem & Chem Engn Div, Dept Med & Proc Chem, San Antonio, TX 78266 USA

[2] Pharmacol Branch, USAMRICD Res Div, Aberdeen Proving Ground, MD 21010 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 07期

关键词：

Acetylcholinesterase; Reactivation; Cyclosarin (GF); GF-inhibited hAChE; Structure-activity relationship; Heteroaryl keto-oximes; ACTING OXIME REACTIVATORS; THERAPEUTIC-EFFICACY; NERVE AGENTS; DELIVERY; KETONES;

D O I：

10.1016/j.bmcl.2014.02.049

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The goal of this research was to identify structurally novel, non-quaternarypyridinium reactivators of GF (cyclosarin)-inhibited hAChE that possess the capacity to mediate in vitro reactivation of GF-inhibited human acetylcholinesterase (hAChE). New compounds were designed, synthesized and assessed in GFinhibited hAChE assays. Structure activity relationships for AChE binding and reactivation of GF-inhibited hAChE were developed. Lead compounds from two different chemical series, represented by compounds 17 and 38, displayed proficient in vitro reactivation of GF- inhibited hAChE, while also possessing low inhibition of native enzyme. (c) 2014 Elsevier Ltd. All rights reserved.

引用

页码：1711 / 1714

页数：4

共 50 条

[41] Synthesis and in vitro evaluation of novel non-oximes for the reactivation of nerve agent inhibited human acetylcholinesterase
de Koning, Martijn C.
Horn, Gabriele
Worek, Franz
van Grol, Marco
CHEMICO-BIOLOGICAL INTERACTIONS, 2020, 326
[42] Synthesis and in vitro kinetic evaluation of N-thiazolylacetamido monoquaternary pyridinium oximes as reactivators of sarin, O-ethylsarin and VX inhibited human acetylcholinesterase (hAChE)
Valiveti, Aditya Kapil
Bhalerao, Uma M.
Acharya, Jyotiranjan
Karade, Hitendra N.
Acharya, Badri Narayan
Raviraju, G.
Halve, Anand K.
Kaushik, Mahabir Parshad
BIOORGANIC & MEDICINAL CHEMISTRY, 2015, 23 (15) : 4899 - 4910
[43] Design and synthesis of new bis-pyridinium oxime reactivators for acetyleholinesterase inhibited by organophosphorous nerve agents
Kim, TH
Kuca, K
Jun, D
Jung, YS
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (11) : 2914 - 2917
[44] Rational design, synthesis and evaluation of smart, uncharged bis-oxime antidotes of OP inhibited human acetylcholinesterase
Radic, Zoran
Gorecki, Lukas
Gerlits, Oksana
Kong, Xiaotian
Cheng, Xiaolin
Blumenthal, Donald
Taylor, Palmer
Ballatore, Carlo
Kovalevsky, Andrey
FASEB JOURNAL, 2020, 34
[45] SULFUR DERIVATIVES OF 2-OXOPROPANAL OXIME AS REACTIVATORS OF ORGANOPHOSPHATE-INHIBITED ACETYLCHOLINESTERASE INVITRO - SYNTHESIS AND STRUCTURE-REACTIVITY RELATIONSHIPS
DEGORRE, F
KIFFER, D
TERRIER, F
JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (04) : 757 - 763
[46] Aminoalkoxy-substituted coumarins: Synthesis and evaluation for reactivation of inhibited human acetylcholinesterase
Elsinghorst, Paul W.
Wille, Timo
Baric, Danijela
Mertens, Matthias D.
Baumann, Madlen
Kueppers, Jim
Guetschow, Michael
ARCHIV DER PHARMAZIE, 2022, 355 (11)
[47] Novel uncharged triazole salicylaldoxime derivatives as potential acetylcholinesterase reactivators: comprehensive computational study, synthesis and in vitro evaluation
Baghersad, Mohammad Hadi
Habibi, Azizollah
Nejad, Arash Dehdashti
RSC ADVANCES, 2023, 13 (41) : 28527 - 28541
[48] Synthesis and in vitro evaluation of xylene linked carbamoyl bis-pyridinium monooximes as reactivators of organophosphorus (OP) inhibited electric eel acetylcholinesterase (AChE)
Acharya, Jyotiranjan
Rana, Hemlata
Kaushik, M. P.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (09) : 3926 - 3933
[49] Rational design, synthesis, and evaluation of uncharged, ?smart? bis-oxime antidotes of organophosphate-inhibited human acetylcholinesterase
Gorecki, Lukas
Gerlits, Oksana
Kong, Xiaotian
Cheng, Xiaolin
Blumenthal, Donald K.
Taylor, Palmer
Ballatore, Carlo
Kovalevsky, Andrey
Radic, Zoran
JOURNAL OF BIOLOGICAL CHEMISTRY, 2020, 295 (13) : 4079 - 4092
[50] In vitro reactivation potency of acetylcholinesterase reactivators -: K074 and K075-: to reactivate tabun-inhibited human brain cholinesterases
Kuca, Kamil
Cabal, Jiri
Jun, Daniel
Musilek, Kamil
NEUROTOXICITY RESEARCH, 2007, 11 (02) : 101 - 106

← 1 2 3 4 5 →