Aminopyridine Carbamic Acid Esters: Synthesis and Potential as Acetylcholinesterase Inhibitors and Acetylcholine Releasers

Reactivity of N-pyridylcarbamates in basic media

“…By comparing the pH-rate profiles of both substrates, one of which is incapable of forming the conjugated anion and is a model for the B AC 2 mechanism (which is easy to distinguish from nucleophilic catalysis using a base and its sterically hindered analogue), 8 one can get a good idea of the E1cB and B AC 2 mechanistic behaviour 9 We have studied the chemistry of new phenyl N-benzoyl-, N-thiobenzoyl-10 and N-arylsulfonyl-carbamates. 11 Based on literature data, 12 which indicate further biological interest in carbamates possessing a pyridine moiety in their structure, we extended our studies to several new N-pyridylcarbamates, 1a-e and 2.…”

Exploring tertiary enamides as versatile synthons in organic synthesis

“…35 The resulting diversely substituted pyridines are very useful in medicinal chemistry, as their analogs have been shown to possess strong acetylcholinesterase (AChE) inhibitory activity. 36 Since the cycloaddition reaction between N-formylmethylsubstituted tertiary enamides and isonitriles initially forms the intermediate B (Scheme 9), termination of the sequential reaction by reduction or hydrolysis of the imino moiety of the presumed intermediate B prior to its oxidative aromatization furnishes functionalized 1,2,3,4-tetrahydropyridines and 2,3dihydropyridin-4(1H)-ones, respectively. As depicted in Scheme 10, Zn(OTf) 2 -mediated reaction between isonitriles and N-formylmethylsubstituted tertiary enamides, followed by reduction with Me 4 NBH(OAc) 3 at ambient temperature produces 1,6-disubstituted trans-3-hydroxy-4-amino-1,2,3,4-tetrahydropyridines 39 in moderate to good yields.…”

Three-component synthesis of nicotinamide derivatives based on cross-recyclization of 2,6-diamino-4-aryl-3,5-dicyano-4H-thiopyrans with acetoacetanilide and alkylating reagents

“…Search for biologically active nicotinamide derivatives is a promising to develop herbicides [1,2] and drugs for Alzheimer's disease treatment [3,4].…”

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Three-component reaction of 2,6-diamino-4-aryl-3,5-dicyano-4H-thiopyrans, acetoacetanilides, and alkylating reagents proceeds via cross-recyclization of thiopyrans to form 6-alkylthio-4-aryl-N-aryl-2-methyl-5-cyanonicotinamides, 3-imino-6-methyl-2-(4-methoxybenzoyl)-4-(3,4-dimethoxyphenyl)-N-phenyl-2,3-dihydrothieno[2,3-b]pyridine-5-carboxamide, and 3-amino-6-methyl-4-(3,4-dimethoxyphenyl)-2-(4-oxo-4H-pyrido[1,2-a]-pyrimidin-2-yl)-N-phenylthieno[2,3-b]pyridine-5-carboxamide.Search for biologically active nicotinamide derivatives is a promising to develop herbicides [1, 2] and drugs for Alzheimer's disease treatment [3,4].Studies on preparation of functionally substituted nicotinamide derivatives [5][6][7][8] showed that cross-recyclization of 2,6-diamino-4-aryl-3,5-dicyano-4H-thiopyrans Ia-Ic with acetoacetanilides IIa and IIb in refluxing ethanol in the presence of an equimolar quantity of triethylamine followed by addition of the alkylating reagent IIIa-IIIe afforded new nicotinamide derivatives such as 6-alkylthio-4,N-diaryl-2-Apparently, the reaction pathway included opening of the thiopyran ring to form intermediate VI that was further transformed into arylmethylidenecyanothioacetamide VIII via malononitrile VII elimination [9][10][11]. The Michael addition of acetoacetanilide II to arylmethylidenecyanothioacetamide VIII led to formation of the corresponding labile adduct IX, which underwent intramolecular heterocyclization to give the substituted pyridine X.

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