Silva_2011_Eur.J.Med.Chem_46_4676

Reference

Title : Synthesis and pharmacological assessment of diversely substituted pyrazolo[3,4-b]quinoline, and benzo[b]pyrazolo[4,3-g][1,8]naphthyridine derivatives - Silva_2011_Eur.J.Med.Chem_46_4676
Author(s) : Silva D , Chioua M , Samadi A , Carmo Carreiras M , Jimeno ML , Mendes E , Rios Cde L , Romero A , Villarroya M , Lopez MG , Marco-Contelles J
Ref : Eur Journal of Medicinal Chemistry , 46 :4676 , 2011
Abstract :

The synthesis and pharmacological analyses of a number of pyrazolo[3,4-b]quinoline and benzo[b]pyrazolo[4,3-g][1,8]naphthyridine derivatives are reported. We have synthesized the diversely substituted tacrine analogues 1-6, by Friedlander-type reaction of readily available o-amino-1-methyl-pyrazole-dicarbonitriles with cyclohexanone. The biological evaluation showed that pyrazolotacrines 1-6 are inhibitors of Electrophorus electricus acetylcholinesterase (EeAChE), in the micromolar range, and quite selective in respect to serum horse butyrylcholinesterase (eqBuChE) inhibition; the most interesting inhibitor is N-(5-amino-1-methyl-6,7,8,9-tetrahydro-1H-benzo[b]pyrazolo[4,3-g][1,8]naphthyridi n-3-yl)acetamide (5) [IC(50) (EeAChE) = 0.069 +/- 0.006 muM; IC(50) (eqBuChE) = 6.3 +/- 0.6 muM]. Kinetic studies showed that compound 5 is a mixed-type inhibitor of EeAChE (K(i) = 155 nM). Inhibitor 5 showed a 45% neuroprotection value against rotenone/oligomycin A-induced neuronal death.

PubMedSearch : Silva_2011_Eur.J.Med.Chem_46_4676
PubMedID: 21715067

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Citations formats

Silva D, Chioua M, Samadi A, Carmo Carreiras M, Jimeno ML, Mendes E, Rios Cde L, Romero A, Villarroya M, Lopez MG, Marco-Contelles J (2011)
Synthesis and pharmacological assessment of diversely substituted pyrazolo[3,4-b]quinoline, and benzo[b]pyrazolo[4,3-g][1,8]naphthyridine derivatives
Eur Journal of Medicinal Chemistry 46 :4676

Silva D, Chioua M, Samadi A, Carmo Carreiras M, Jimeno ML, Mendes E, Rios Cde L, Romero A, Villarroya M, Lopez MG, Marco-Contelles J (2011)
Eur Journal of Medicinal Chemistry 46 :4676