In vivo evaluation of diaminodiphenyls: Anticonvulsant agents with minimal acute neurotoxicity

doi:10.1016/j.bmcl.2009.07.059

Bioorganic & Medicinal Chemistry Letters

Volume 19, Issue 17, 1 September 2009, Pages 5012-5015

https://doi.org/10.1016/j.bmcl.2009.07.059 Get rights and content

Abstract

Several diaminodiphenyl analogs were assessed in vivo for their capacity to inhibit seizure induction and propagation in rodents. Both 3,4′- and 4,4′-diaminodiphenyl compounds prevented seizures for as long as 4 h after maximal electric shock induction. 4,4′-Diphenyl compounds bridged by a methylene, sulfide, or carbonyl linker also attenuated focal seizure acquisition in a kindling model. Of these analogs, based upon data generated in two rodent species, 4,4′-thiodianiline (1) was identified as the most active compound, significantly reducing seizure staging scores and after-discharge duration for several hours after systemic administration. All compounds were devoid of acute in vivo neurotoxicity at doses well above those required for anticonvulsant activity.

Graphical abstract

Diaminodiphenyl compounds 1–6 exert in vivo anticonvulsant activity with minimal acute neurotoxicity.

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Acknowledgment

The authors gratefully acknowledge the NINDA Anticonvulsant Screening Program, with special thanks to Dr. H.S. White.

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In vivo evaluation of diaminodiphenyls: Anticonvulsant agents with minimal acute neurotoxicity

Abstract

Graphical abstract

Section snippets

Acknowledgment

Bioorg. Med. Chem. Lett.

Epilepsy Res.

Pharmacol. Biochem. Behav.

Epilepsy Res.

Electroenceph. Clin. Neurophys.

Epilepsia

Drugs

Paediatr. Child Health