Aminopyridazines as acetylcholinesterase inhibitors.

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Contreras JM, Rival YM, Chayer S, Bourguignon JJ, Wermuth CG

Aminopyridazines as acetylcholinesterase inhibitors.

J Med Chem. 1999 Feb 25;42(4):730-41.

PubMed ID

10052979 [ View in PubMed

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Abstract

Following the discovery of the weak, competitive and reversible acetylcholinesterase (AChE)-inhibiting activity of minaprine (3c) (IC50 = 85 microM on homogenized rat striatum AChE), a series of 3-amino-6-phenylpyridazines was synthesized and tested for inhibition of AChE. A classical structure-activity relationship exploration suggested that, in comparison to minaprine, the critical elements for high AChE inhibition are as follows: (i) presence of a central pyridazine ring, (ii) necessity of a lipophilic cationic head, (iii) change from a 2- to a 4-5-carbon units distance between the pyridazine ring and the cationic head. Among all the derivatives investigated, 3-[2-(1-benzylpiperidin-4-yl)ethylamino]-6-phenylpyridazine (3y), which shows an IC50 of 0.12 microM on purified AChE (electric eel), was found to be one of the most potent anti-AChE inhibitors, representing a 5000-fold increase in potency compared to minaprine.1

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Minaprine	Acetylcholinesterase	Protein	Humans	Yes	Inhibitor	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Donepezil	Acetylcholinesterase	IC 50 (nM)	16	N/A	N/A	Details
Tacrine	Acetylcholinesterase	IC 50 (nM)	95	N/A	N/A	Details