Substituted 2-Aminothiopen-derivatives: A potential new class of GluR6-Antagonists

Briel, D.; Rybak, Anastasiya; Kronbach, Christiane; Unverferth, K.

doi:10.1016/j.ejmech.2009.09.025

Cited by 41 publications

(19 citation statements)

References 21 publications

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“…Intermediates 22 and 24 were prepared via Gewald reaction [25, 26] which involves condensation of appropriate aldehydes ( 20 ) or ketones ( 22 ) with ethyl cyanoacetate in presence of an elemental sulfur and base (Scheme 2A). All intermediates 25 are commercially available.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H

Kankanala

Kirby

Huber

et al. 2017

European Journal of Medicinal Chemistry

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Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only HIV enzymatic function not targeted by current antiviral drugs. Although various chemotypes have been reported to inhibit HIV RNase H, few have shown significant antiviral activities. We report herein the design, synthesis and biological evaluation of a novel N-hydroxy thienopyrimidine-2,3-dione chemotype (11) which potently and selectively inhibited RNase H with considerable potency against HIV-1 in cell culture. Current structure-activity-relationship (SAR) identified analogue 11d as a nanomolar inhibitor of RNase H (IC50 = 0.04 μM) with decent antiviral potency (EC50 = 7.4 μM) and no cytotoxicity (CC50 > 100 μM). In extended biochemical assays compound 11d did not inhibit RT polymerase (pol) while inhibiting integrase strand transfer (INST) with 53 fold lower potency (IC50 = 2.1 μM) than RNase H inhibition. Crystallographic and molecular modeling studies confirmed the RNase H active site binding mode.

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Section: Resultsmentioning

confidence: 99%

Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H

Kankanala

Kirby

Huber

et al. 2017

European Journal of Medicinal Chemistry

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“…By employing a modification of the self-condensation reaction conditions reported earlier by Elnagdi et al [18] (Scheme 5) and Breil et al . [19], heating 3b and 3c over activated zeolite was found to lead to formation of the corresponding arenes 23b and 23c via a route possiblly involving the intermediacy of 22 .…”

Section: Resultsmentioning

confidence: 99%

Studies on 3-Oxoalkanenitriles: Novel Rearrangement Reactions Observed in Studies of the Chemistry of 3-Heteroaroyl-3-Oxoalkanenitriles as Novel Routes to 2-Dialkylaminopyridines

et al. 2012

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3-Aroyl and 3-heteroaroyl substituted 3-oxoalkanenitriles were synthesized by the reactions of activated aromatic and hetero-aromatic substances with cyanoacetic acid in the presence of acetic anhydride. As part of studies focusing on the preparation of cyanoacetyl-1-N-methylbenzimidazole, we observed that reaction of N-methyl-benzimidazole with the cyanoanhydride formed by condensation of cyanoacetic acid with acetic anhydride, leads to the formation of 2-(1,3-diacetyl-2,3-dihydro-1H-benzo[d]-imidazol-2-yl)acetonitrile (5), whose structure was confirmed by X-ray crystallographic analysis. 3-Oxoalkanenitriles 3a,b were observed to undergo condensation reactions with dimethylformamide dimethyl acetal (DMFDMA) to afford the corresponding enamino-nitriles, which react with malononitrile to give 2-dialkylaminopyridines through a pathway involving a new, unexpected rearrangement process. Reactions of 3-oxoalkanenitriles with ethyl acetoacetate were found to afford 2-oxopyran-3-carbonitriles, also occurring via this unexpected rearrangement process. Mechanisms to account for both rearrangement reactions are suggested. In addition, reactions of 3-oxoalkanenitriles with acetylacetone in acetic acid in the presence of ammonium acetate result in the formation of pyridine-3-carbonitriles. Finally, upon heating in the presence of zeolite 3-oxoalkanenitriles 3b,c self-trimerized to produce the corresponding aniline derivatives 23b,c.

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“…4.0 ppm [29,32]. The prevalence of the 3H-rather than the 1H-form in a number of 2-(alkylthio)uracils is well documented [20][21][22]28,[33][34][35]. Consequently, it is not unreasonable to conclude that our studied alkylation reactions take place with complete selectivity, since the site of alkylation is initially the sulfur rather than the nitrogen and in the case of the disubstituted products the N-3 is the second position for alkylation.…”

Section: Chemistrymentioning

confidence: 76%

Regioselective synthesis and antimicrobial studies of novel bridgehead nitrogen heterocycles containing the thienopyrimidinone skeleton

Gaber

Moussa

2011

Eur. J. Chem.

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KEYWORDSVersatile 2-(alkylthio)pyrimidine-type and 2-(phenacylamino)thiophene building blocks (4ad) and 16 were obtained based on an ortho functionalized thiophene derivative 1. A novel series of thieno[2,3-d]pyrimidin-4-one derivatives with annelated bridgehead nitrogen heterocycles was synthesized starting from precursors 4 and 16 through convenient methods. Cyclocondensation of 2-(phenacylthio)pyrimidinone derivative (4b) with sulfuric acid led to the tricyclic thiazole derivative 5. Initial hydrazinolysis of 3-(carbethoxymethyl)pyrimidinone derivative (4d) followed by nitrous acid deamination of the formed N-aminolactam (7) to obtain a N-protodeamino analogue 8a, which on further treatment with formaldehyde and piperidine yielded the respective Mannich-type base 8b. On the other hand, initial hydrazinolysis of 3-unsubstituted pyrimidinone derivative 4a and subsequent acetylation gave the condensed 3-methyltriazole derivative 12, whereas the condensed pyrrole derivative 19 was obtained by heterocyclization of 2-phenacylamine derivative 16 with malononitrile. All newly-obtained thienopyrimidinones with annelated bridgehead nitrogen were screened for their antimicrobial activity against strains of a representative panel of Gram-positive and Gram-negative bacteria as well as fungi together with reference drugs. The compounds under investigation displayed generally good in vitro antibacterial and antifungal activities, with compound 8b that has a N-piperidinylmethyl moiety showing essentially the highest inhibition in both assays. Despite promising antimicrobial activity of N-1-substituted imidazole derivative 8b, the corresponding N-1-unsubstituted analogue 8a displayed poor activity. The heteroannelation of a N-(piperidinylmethyl)imidazole or 3-methyltriazole moiety to the thienopyrimidinone scaffold could be considered as a potential strategy for the development of new therapeutic antimicrobial agents.Thienopyrimidinone Alkylation Cyclodehydration Hydrazinolysis Acetylation Antimicrobial activity

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Substituted 2-Aminothiopen-derivatives: A potential new class of GluR6-Antagonists

Cited by 41 publications

References 21 publications

Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H

Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H

Studies on 3-Oxoalkanenitriles: Novel Rearrangement Reactions Observed in Studies of the Chemistry of 3-Heteroaroyl-3-Oxoalkanenitriles as Novel Routes to 2-Dialkylaminopyridines

Regioselective synthesis and antimicrobial studies of novel bridgehead nitrogen heterocycles containing the thienopyrimidinone skeleton

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