Approaches to 1,1-disubstituted cinnolin-3-ylio oxides: synthesis and reactivity of a new class of heterocyclic betaines

Arán, Vicente J.; Asensio, Juan Luis; Molina, José Luis Malo de; Muñoz, Pilar; Ruíz, José Rafael; Stud, M.

doi:10.1039/a701103b

Cited by 19 publications

(12 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to test the potential of TOMOCOMD-CARDD method and LDA for detecting novel antiprotozoal leads, we predicted the biological activity of all the chemicals contained in our 'in-house' collections of indazole, indole, cinnoline and quinoxaline derivatives, which have been recently obtained by our chemical synthesis team [67,[77][78][79][80][81][82][83][84]. On the basis of computer-aided predictions we selected potential trichomonacidal compounds (virtual hits).…”

Section: Ligand-based Virtual In Silico Screening and Lead Trichomonamentioning

confidence: 99%

A Computer-Based Approach to the Rational Discovery of New Trichomonacidal Drugs by Atom-Type Linear Indices

Marrero-Ponce¹,

Machado-Tugores²,

Pereira³

et al. 2005

CDDT

View full text Add to dashboard Cite

Computational approaches are developed to design or rationally select, from structural databases, new lead trichomonacidal compounds. First, a data set of 111 compounds was split (design) into training and predicting series using hierarchical and partitional cluster analyses. Later, two discriminant functions were derived with the use of non-stochastic and stochastic atom-type linear indices. The obtained LDA (linear discrimination analysis)-based QSAR (quantitative structure-activity relationship) models, using non-stochastic and stochastic descriptors were able to classify correctly 95.56% (90.48%) and 91.11% (85.71%) of the compounds in training (test) sets, respectively. The result of predictions on the 10% full-out cross-validation test also evidenced the quality (robustness, stability and predictive power) of the obtained models. These models were orthogonalized using the Randic orthogonalization procedure. Afterwards, a simulation experiment of virtual screening was conducted to test the possibilities of the classification models developed here in detecting antitrichomonal chemicals of diverse chemical structures. In this sense, the 100.00% and 77.77% of the screened compounds were detected by the LDA-based QSAR models (Eq. 13 and Eq. 14, correspondingly) as trichomonacidal. Finally, new lead trichomonacidals were discovered by prediction of their antirichomonal activity with obtained models. The most of tested chemicals exhibit the predicted antitrichomonal effect in the performed ligand-based virtual screening, yielding an accuracy of the 90.48% (19/21). These results support a role for TOMOCOMD-CARDD descriptors in the biosilico discovery of new compounds.

show abstract

Section: Ligand-based Virtual In Silico Screening and Lead Trichomonamentioning

confidence: 99%

A Computer-Based Approach to the Rational Discovery of New Trichomonacidal Drugs by Atom-Type Linear Indices

Marrero-Ponce¹,

Machado-Tugores²,

Pereira³

et al. 2005

CDDT

View full text Add to dashboard Cite

show abstract

“…In recent years, we have developed different methods of the synthesis of indazoles, [1][2][3][4] indoles, [5] cinnolines [6] and quinoxalines.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of 1,1′‐Hydrocarbylenebis(indazol‐3‐ols) as Potential Antimalarial Drugs

et al. 2009

View full text Add to dashboard Cite

Bis(indazol-3-ol) derivatives (5, 30-38) were prepared by alkylation of 3-alkoxyindazoles with alpha,omega-dibromides, followed by removal of the O-protecting groups. These compounds were subsequently evaluated as inhibitors of biocrystallization of ferriprotoporphyrin IX (heme) to hemozoin, a Plasmodium detoxification specific process. Most bis(5-nitroindazol-3-ols) were good inhibitors, however, a denitro analogue (38), the intermediate bis(3-alkoxyindazoles) (15-29) as well as bis(indazolin-3-ones) (39-42) were not active, showing the importance of the NO(2) and OH groups in the inhibition process.

show abstract

“…as an example of applicability of our approach, we selected a series of ten new synthesized heterocyclic compounds obtained in one of our research groups. [48][49][50][51] As first step of this virtual screening, all structures were drawn using de drawing mode activity. 52 However, once this first assays have been performed, more selective methods are required to determine the activity of novel compounds.…”

Section: Resultsmentioning

confidence: 99%

A novel non-stochastic quadratic fingerprints-based approach for the ‘in silico’ discovery of new antitrypanosomal compounds

Montero-Torres

Gómez²,

Marrero-Ponce

et al. 2005

Bioorganic & Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Approaches to 1,1-disubstituted cinnolin-3-ylio oxides: synthesis and reactivity of a new class of heterocyclic betaines

Cited by 19 publications

References 7 publications

A Computer-Based Approach to the Rational Discovery of New Trichomonacidal Drugs by Atom-Type Linear Indices

A Computer-Based Approach to the Rational Discovery of New Trichomonacidal Drugs by Atom-Type Linear Indices

Synthesis and Evaluation of 1,1′‐Hydrocarbylenebis(indazol‐3‐ols) as Potential Antimalarial Drugs

A novel non-stochastic quadratic fingerprints-based approach for the ‘in silico’ discovery of new antitrypanosomal compounds

Contact Info

Product

Resources

About