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Synthesis, biological evaluation and molecular modeling study of some new thiazolodiazepine analogs as CNS active agents.

Abstract：

:New derivatives of ethyl 8-oxo-5,6,7,8-tetrahydro-thiazolo[3,2-a][1,3]diazepin-3-carboxylate (HIE-124, 3), were synthesized as continuation to our previous patented efforts. Compounds 15 and 20 showed marginal hypnotic potency compared to 3. Compounds 15 (0.78mmol/kg) and 20 (0.39mmol/kg) showed remarkable 100% protection against PTZ induced convulsions with two and four fold increase in activity than sodium valproate (1.38mmol/kg), respectively. Molecular modeling studies showed hydrogen bonding interaction between 15 and Thr56 residues at the binding site of GABAA. Superposition, flexible alignment and surface mapping of 15, 20 and diazepam supports their biological resemblance where ADMET study suggested that those compounds could be used as oral anticonvulsants.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Al-Rashood STA,Hassan GS,El-Messery SM,El-Taher KEH,Hefnawy MM,Al-Omar MA,El-Subbagh HI

doi

10.1016/j.bmcl.2015.11.097

subject

Has Abstract

pub_date

2016-01-15 00:00:00

pages

445-453

issue

2

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)30305-X

journal_volume

26

pub_type

杂志文章

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