Structure-Activity Study on Anticonvulsant (Thio) Hydantoins Using Molecular Connectivity Indices

Dang, Poonam; Мадан, А. К.

doi:10.1021/ci00021a024

Cited by 31 publications

(21 citation statements)

References 6 publications

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“…Melting points were measured on a hot stage Boetius apparatus and are uncorrected. The 1 H nmr and 13 C nmr spectra were acquired on a Bruker 500 apparatus, using CDCl 3 (for 1 -6, 10, and 11) or D M S O -d 6 (for 9, 1 2 -1 9) and TMS as internal standard. Coupling constants are given in Hz.…”

Section: J Heterocyclic Chem 40 665(2003)mentioning

confidence: 99%

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Synthesis of 3‐Ω‐amino‐2‐thiohydantoins

Ryczek

2003

Journal of Heterocyclic Chem

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In the reaction of ethyl isothiocyanatoacetate with diamines, followed by cyclization of the intermediate product, 3-monosubstituted thiohydantoins have been obtained. It was found that the reaction course depends on the purity of the isothiocyanate used and also, in the case of dialkylaminoamines, the selfcyclization occurs. Besides the dialkylamino derivatives of 3-monosubstituted 2-thiohydantoins also new monoalkylamino, amino and heterocyclic derivatives were synthesized. The aryldiazonium derivative of 3-monosubstituted 2-thiohydantoin yielded both respective phenol derivative after hydrolysis and the product of coupling with 2-naphthol.J. Heterocyclic Chem., 40, 665(2003).2-Thiohydantoins, in common with their 2-oxo analogs, have interesting pharmacological activity [1-3], technical applications [4,5] and properties [6,7]. Investigations on these compounds is less active in comparison to hydantoins due to their difficult synthesis and higher toxicity. A relatively small number of 3-monosubstituted 2-thiohydantoins have been synthesized to date, and only a few among them possess dialkylamino substituents [8][9][10]. 2-Thiohydantoins with amino or hydroxy group in the substituent in 3 position are not reported in the literature. This is due mainly to diff iculty of synthesis, because it is impossible to obtain aliphatic or aromatic isothiocyanates with a free amino group, as well as aliphatic ones with hydroxy group. Such isothiocyanates are pre-requisite in the standard synthesis [ 11] of 3-monosubstituted 2-thiohydantoins.Results and Discussion.The dialkylamino, amino and hydroxy derivatives of 3-monosubstituted 2-thiohydantoin described in this paper were obtained by the literature method [12] using ethyl isothiocyanatoacetate and respective diamine, aminoalcohol or aminophenol. Mass spectrometry investigations showed that the starting isothiocyanate contains small amounts of thiophosgene and carbon disulfide. These contaminants could not be removed from the reagent obtained according to literature [13] by standard procedures like vacuum distillation (an azeotrope was formed).It was found that these minor contaminants markedly influence the reaction, yielding tar-like products of unidentified composition. Using highly pure isothiocyanate, obtained by removal of contaminants by purging with

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Section: J Heterocyclic Chem 40 665(2003)mentioning

confidence: 99%

“…2-Thiohydantoins, in common with their 2-oxo analogs, have interesting pharmacological activity [1-3], technical applications [4,5] and properties [6,7]. Investigations on these compounds is less active in comparison to hydantoins due to their difficult synthesis and higher toxicity.…”

mentioning

confidence: 99%

Synthesis of 3‐Ω‐amino‐2‐thiohydantoins

Ryczek

2003

Journal of Heterocyclic Chem

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“…Great progress has been made in experimental and theoretical investigations of the protonation and deprotonation of heterocyclic compounds. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Most of these studies have been carried out to predict the correct protonation and deprotonation sites and the possible role played by the protonation and deprotonation process in the isomerization process.…”

Section: Introductionmentioning

confidence: 99%

Tautomeric Study of Neutral, Protonated and Deprotonated Isorhodanine Based on High Level Density Functional Theory

Safi¹

2016

Orient. J. Chem

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High level Density Functional Theory (DFT) using B3LYP/6-311++G(2df,2p)//6-311+G(d,p) calculations on the relative stabilities and structures of the neutral, protonated and deprotonated isorhodanine tautomeric forms are reported in the gas phase and solution. Gas phase and solution B3LYP calculations predict that the oxo/thione tautomer is the most stable one in all cases. Comparison of the gas phase results, bond lengths, bond angles and relative energies, with those of the solution reveals very strong linear relationships. Results of the calculated proton affinities (PAs), molecular gas phase basicity (GBs) and deprotonation enthalpies (DH dep ) indicate that isorhodanine behaves as a sulfur base. The isomerization processes leading from the most stable species to the less stable ones are also investigated.

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“…These include Wieners index [4,5], Balabans index [6], Hosoyas index [7], molecular connectivity indices [8] and eccentric connectivity index [9 -12]. Use of topological indices in structure-activity relationship studies seems to play an important role in situations where biological activity is determined predominantly by topological architecture of molecular structure, i.e., where simple connectivity among neighboring atoms, without considering the chemical nature of atom or nature of chemical bonding, may be the major determinant of biological activity of a molecule [13].…”

Section: Introductionmentioning

confidence: 99%

Model for Prediction of Anti‐HIV Activity of 2‐Pyridinone Derivatives Using Novel Topological Descriptor

et al. 2006

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A novel highly discriminating adjacency-cum-distance based topological descriptor, termed as augmented eccentric connectivity index, has been conceptualized and its discriminating power investigated with regard to anti-HIV activity of 2-pyridinone derivatives. The discriminating power of the augmented eccentric connectivity index was found to be far superior when compared to that of the distance based Wieners index and adjacency based molecular connectivity index. This index did not exhibit any degeneracy amongst all possible structures with three, four and five vertices. The values of augmented eccentric connectivity index, Wieners index and first-order molecular connectivity index of each of the 72 3-aminopyridin-2(1H)-one analogues comprising the dataset were computed using in-house computer program. The resulting data was analyzed and suitable models were developed after identification of the active ranges. Subsequently, a biological activity was assigned to each of the compounds involved in the dataset using these models which was then compared with the reported anti-HIV activity. High degree of prediction ranging from 81% to 89% was observed using models based upon these topological descriptors. Exceptionally high discriminating power amalgamated with decreased degeneracy of the proposed index, offers a vast potential for structure-activity/property studies.

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Structure-Activity Study on Anticonvulsant (Thio) Hydantoins Using Molecular Connectivity Indices

Cited by 31 publications

References 6 publications

Synthesis of 3‐Ω‐amino‐2‐thiohydantoins

Synthesis of 3‐Ω‐amino‐2‐thiohydantoins

Tautomeric Study of Neutral, Protonated and Deprotonated Isorhodanine Based on High Level Density Functional Theory

Model for Prediction of Anti‐HIV Activity of 2‐Pyridinone Derivatives Using Novel Topological Descriptor

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