Classical and Fragment-Based Hologram Structure-Activity Relationships for a Series of Analgesic Cyclic Imides

Andricopulo, Adriano D.; Borchhardt, Deise M.; Castilho, Marcelo Santos

doi:10.2174/157018008783406723

Cited by 3 publications

(1 citation statement)

References 15 publications

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“…The imide core is also present in compounds whose activity is related to CNS activity [ 32 , 33 , 34 , 35 , 36 ]. In particular, much attention has been paid to their ability to inhibit cyclooxygenases, anti-inflammatory, and analgetic activity [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. To date, several drugs with cyclic imide structure have been approved, including lurasidone, buspirone, ethosuximide, mesuximide, and the IMiDs class includes thalidomide and its analogues lenalidomide, pomalidomide, apremilast ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

Redzicka

Czyżnikowska

Wiatrak

et al. 2021

IJMS

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In the present paper, we describe the biological activity of the newly designed and synthesized series N-substituted 3,4-pyrroledicarboximides 2a–2p. The compounds 2a–2p were obtained in good yields by one-pot, three-component condensation of pyrrolo[3,4-c]pyrrole scaffold (1a–c) with secondary amines and an excess of formaldehyde solution in C2H5OH. The structural properties of the compounds were characterized by 1H NMR, 13C NMR FT-IR, MS, and elemental analysis. Moreover, single crystal X-ray diffraction has been recorded for compound 2h. The colorimetric inhibitor screening assay was used to obtain their potencies to inhibit COX-1 and COX-2 enzymes. According to the results, all of the tested compounds inhibited the activity of COX-1 and COX-2. Theoretical modeling was also applied to describe the binding properties of compounds towards COX-1 and COX-2 cyclooxygenase isoform. The data were supported by QSAR study.

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Section: Introductionmentioning

confidence: 99%

Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

Redzicka

Czyżnikowska

Wiatrak

et al. 2021

IJMS

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Fragment-based QSAR: perspectives in drug design

Salum

Andricopulo

2009

Mol Divers

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Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate the optimization of leads into drug candidates. Quantitative structure-activity relationship (QSAR) methods are among the most important strategies that can be applied for the successful design of small molecule modulators having clinical utility. Hologram QSAR (HQSAR) is a modern 2D fragment-based QSAR method that employs specialized molecular fingerprints. HQSAR can be applied to large data sets of compounds, as well as traditional-size sets, being a versatile tool in drug design. The HQSAR approach has evolved from a classical use in the generation of standard QSAR models for data correlation and prediction into advanced drug design tools for virtual screening and pharmacokinetic property prediction. This paper provides a brief perspective on the evolution and current status of HQSAR, highlighting present challenges and new opportunities in drug design.

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CoMFA and CoMSIA 3D QSAR Models for a Series of Cyclic Imides with Analgesic Activity

Borchhardt

Andricopulo²

2009

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Three-dimensional quantitative structure-activity relationships (3D-QSAR) were performed for a series of analgesic cyclic imides using the CoMFA and CoMSIA methods. Significant correlation coefficients (CoMFA, r2 = 0.95 and q2 = 0.72; CoMSIA, r2 = 0.96 and q2 = 0.76) were obtained, and the generated models were externally validated using test sets. The final QSAR models as well as the information gathered from 3D contour maps should be useful for the design of novel cyclic imides having improved analgesic activity.

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Classical and Fragment-Based Hologram Structure-Activity Relationships for a Series of Analgesic Cyclic Imides

Cited by 3 publications

References 15 publications

Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

Fragment-based QSAR: perspectives in drug design

CoMFA and CoMSIA 3D QSAR Models for a Series of Cyclic Imides with Analgesic Activity

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