Evidence mapPaperPMID 36846367Full record

ReviewRSC medicinal chemistry2023

Nitriles: an attractive approach to the development of covalent inhibitors.

Vinícius Bonatto, Rafael F Lameiro, Fernanda R Rocho, Jerônimo Lameira, Andrei Leitão, Carlos A Montanari

Abstract readReview
In one paragraph

Review in RSC medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Potent and Selective Human 5-HTJournal of medicinal chemistry · 2024
    Article
  17. Article
  18. Advances in the Search for SARS-CoV-2 MPathogens (Basel, Switzerland) · 2024
    Review
  19. Review
  20. The Nitrile Bis-Thiol Bioconjugation Reaction.Journal of the American Chemical Society · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Vinícius BonattoMedicinal and Biological Chemistry Group, São Carlos Institute of Chemistry, University of São Paulo Avenue Trabalhador Sancarlense, 400 13566-590 São Carlos/SP Brazil carlos.montanari@usp.br.ORCID https://orcid.org/0000-0002-3119-0447
Rafael F LameiroMedicinal and Biological Chemistry Group, São Carlos Institute of Chemistry, University of São Paulo Avenue Trabalhador Sancarlense, 400 13566-590 São Carlos/SP Brazil carlos.montanari@usp.br.
Fernanda R RochoMedicinal and Biological Chemistry Group, São Carlos Institute of Chemistry, University of São Paulo Avenue Trabalhador Sancarlense, 400 13566-590 São Carlos/SP Brazil carlos.montanari@usp.br.
Jerônimo LameiraMedicinal and Biological Chemistry Group, São Carlos Institute of Chemistry, University of São Paulo Avenue Trabalhador Sancarlense, 400 13566-590 São Carlos/SP Brazil carlos.montanari@usp.br.ORCID https://orcid.org/0000-0001-7270-1517
Andrei LeitãoMedicinal and Biological Chemistry Group, São Carlos Institute of Chemistry, University of São Paulo Avenue Trabalhador Sancarlense, 400 13566-590 São Carlos/SP Brazil carlos.montanari@usp.br.ORCID https://orcid.org/0000-0002-6601-6609
Carlos A MontanariMedicinal and Biological Chemistry Group, São Carlos Institute of Chemistry, University of São Paulo Avenue Trabalhador Sancarlense, 400 13566-590 São Carlos/SP Brazil carlos.montanari@usp.br.ORCID https://orcid.org/0000-0002-4963-0316

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nitriles have broad applications in medicinal chemistry, with more than 60 small molecule drugs on the market containing the cyano functional group. In addition to the well-known noncovalent interactions that nitriles can perform with macromolecular targets, they are also known to improve drug candidates' pharmacokinetic profiles. Moreover, the cyano group can be used as an electrophilic warhead to covalently bind an inhibitor to a target of interest, forming a covalent adduct, a strategy that can present benefits over noncovalent inhibitors. This approach has gained much notoriety in recent years, mainly with diabetes and COVID-19-approved drugs. Nevertheless, the application of nitriles in covalent ligands is not restricted to it being the reactive center, as it can also be employed to convert irreversible inhibitors into reversible ones, a promising strategy for kinase inhibition and protein degradation. In this review, we introduce and discuss the roles of the cyano group in covalent inhibitors, how to tune its reactivity and the possibility of achieving selectivity only by replacing the warhead. Finally, we provide an overview of nitrile-based covalent compounds in approved drugs and inhibitors recently described in the literature.

Identifiers

PMID36846367
PMCPMC9945868

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.