Microwave-assisted synthesis and structure-activity relationships of neuroactive pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives.
We described herein the optimization of the synthetic methodology exploited to obtain the pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine sedative prototype 1a and novel analogues designed by successive molecular simplifications. By applying microwave irradiation during the hetero Diels-Alder key-step to obtain the heterotricyclic scaffold, under solvent-free conditions, we were able to obtain the desired compounds in drastically shorter times and better yields. Additionally, in vivo evaluation of the sedative effects of these heterocyclic derivatives showed that 1a and the novel structurally-related analogue 1e were the most efficient compounds to impair the locomotor activity in mice at the dose of 10micromol/kg.
Nascimento-Júnior
Nailton M
NM
Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, PO Box 68023, Rio de Janeiro 21941-902, RJ, Brazil.
Mendes
Thaiana C F
TC
Leal
Daniella M
DM
Corrêa
Claudia Maria N
CM
Sudo
Roberto T
RT
Zapata-Sudo
Gisele
G
Barreiro
Eliezer J
EJ
Fraga
Carlos A M
CA
D000818:Animals; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008872:Microwaves; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D006575:Heterocyclic Compounds, 3-Ring; D018696:Neuroprotective Agents; D011725:Pyridines