Pyridofuropyrrolo[1,2-a]pyrimidines and pyridofuropyrimido[1,2-a]azepines: new chemical entities (NCE) with anticonvulsive and psychotropic properties

Abstract

Herein we report the synthesis of several new condensed furo [2,3-b]pyridines 3 from the 3-oxo derivatives of cyclopenta[c]pyridine, of 5,6,7,8-tetrahydroisoquinoline and of pyrano[3,4-c]pyridine 1. The obtained furo[2,3-b]pyridines 3 were used as starting materials for the synthesis of pyridofuropyrrolo[1,2-a] pyrimidines 4 and of pyridofuropyrimido[1,2-a]azepines 5. Interestingly enough, derivatives of pyridofuropyrimido[1,2-a]azepines 5 exhibited anticonvulsant activity significantly better than that of the commercial drug ethosuximide (zarontin). Some of them showed a sedative effect, unlike ethosuximide. Scheme 2 Synthesis of furopyrrolo[1,2-a]pyrimidines 4 and furopyrimido[1,2-a]azepines 5. 49030 | RSC Adv., 2016, 6, 49028-49038 This journal isPrediction of biological activity spectra for the designed in silico compounds was performed by PASS version 2014.This version of PASS predicts simultaneously about 7000 types of biological activities with mean accuracy $95% based on analysis of structure-activity relationships for the training set, including information about 1 000 000 substances. The PASS This journal is

Synthesis of New Heterocyclic Systems: Pyrido[3′,2′:4,5]thieno(furo)[2,3‐e][1,2,4]triazolopyrimidines and an Unusual ANRORC Rearrangement in the Fused Pyrimidine Series

“…As starting compounds ethyl 1‐aminofuro(thieno)[2,3‐ b ]pyridine‐2‐carboxylates 1 a − h ,− were used (Figure ).…”

“…Compounds 1 a − h reacted with benzoyl isothiocyanate in benzene, giving the polyfunctionalized thioureido derivatives 2 a – h ,, prone to furnish further cyclization reaction (Scheme , Table ). Thus, compounds 2 by intramolecular cyclization under the action of potassium hydroxide in ethanol furnished the 9(10)‐thioxopyrido[3′,2′:4,5]thieno(furo)[3,2‐ d ]pyrimidin‐7(8)‐ones 3 a – h in very high yields (Scheme ).…”

“…For example, the bicyclic pyrano[3,4‐ c ]pyridines show high cardiotonic activity, the tricyclic fused pyrazolo[3,4‐ b ]pyridines display anticonvulsant activity and are EPHA4 inhibitors, while the tetracyclic derivatives of pyrido[3′,2′:4,5]thieno(furo)[3,2‐ d ]pyrimidine appear to be able to interact with a number of molecular targets including phosphodiesterase IV with potential use in the treatment of asthma and chronic obstructive pulmonary disease, release control of tumor necrosis factor‐α (TNFα), beta2 adrenoreceptor agonist activity and pronounced antimicrobial activity . Finally the pentacyclic derivatives of pyrido[3′,2′:4,5]furo[3,2‐ d ]pyrimidines exhibit pronounced neurotropic activity …”

Synthesis of 1-Amino-3-oxo-2,7-naphthyridines via Smiles Rearrangement: A New Approach in the Field of Chemistry of Heterocyclic Compounds

“…Furthermore, it is well known that fused derivatives of furo[2,3- b ]pyridine show high biological activity [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Along this line we have previously synthesized several condensed furo[2,3- b ]pyridines based on the cyclopenta[ c ]pyridines, 5,6,7,8-tetrahydroisoquinolines and pyrano[3,4- c ]pyridines, obtaining compounds with neurotropic [ 25 , 26 ], antimicrobial [ 27 ], antitumor [ 28 ] and potent antiviral [ 29 ] activities.…”