基于GABA受体的药物设计概要

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O R
1
O R
1
S R
2
O P O O
O O
R
1
R S
2
R
1
O R O
2
Butyl benzoates
Modification of GABA Antagonists
3
H O O
3
H
O
[3H]EBOB
O O
COOH
Inhibition of [3H]EBOB Binding LC50rat = 1.41 mM, LC50fly = 2.90 mM
Cl Cl Cl lindane
O O S O
a-endosulfan
DTD
Polychlorated Cyclanes
O O O O O MeO O O O OH MeO O O OH O O O O O OH
picrotoxinin
picrodendrin-Q
tuti
Picrodendrin Homologues
R
O O P S O
wk.baidu.com
3
O
R
4
O P S O
Bicyclic GABA Antagonists
O P S O O
Nematocidal Activity LD50 = 24.7 mM
O O P S O
O O P S O
LC50 rat / LC50 housefly = 2360 nM / 45 nM = 52 (in vitro）
LD50housefly = 0 . 0 4 mg/fly（in vivo）
Compound 15
B A O C
P S O O
Presumption of Binding Sites
A
O
B
C
O O
EBOB
Presumption of Binding Sites
B A R
1
D
O R C O
2
Possible Interaction of GABA Antagonists with Their Binding Sites
Housefly Rat
Comparison of Housefly and Rat GABA Receptors
Summary
GABA receptor is one of the important target for developing insecticides. Electrophysiological, biochemical, and pharmacological studies have indicated that a number of differences exist between insect and vertebrate GABA receptors. Exploring such differences by 3DQSAR may develop safer insecticide.
基于GABA受体的药物设计
巨修练
武汉工程大学
GABA(g-aminobutyric acid)
O H2N OH
Model of GABA Receptor
Cl-
Model of Cl- Channel
Cl Cl Cl
Cl Cl Cl Cl
Cl Cl
R6 R4 R3 R2
R5 R1 O O R7
O Cl N CF 3 Cl fipronil N SOCF 3 NH 2 CN N S
O
O O
N N N
LY219048
U-93631
Phenylpyrazoles
O O O TBPS P S O
O O EBOB
O O P O dioxaphosphorinane
Br
Trioxabicyclooctanes
Cl N N F3C O Cl O
Compound 14
Lowest Energy Conformation of Compound 14
Alignment of The Training Set
Pharmacophore Map of Housefly GABA Receptor
Pharmacophore Map of Rat GABA Receptor