Synthesis, molecular modeling studies and bronchodilation properties of nicotinonitrile containing-compounds

E. A. Soliman, Siva Shankar Panda, Marian N. Aziz, El Sayed M. Shalaby, Nawal Mishriky, Fahmy M. Asaad, Adel S. Girgis

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Facile synthetic pathway for nicotinonitriles 5a‒o, 7a‒i was demonstrated through reaction of ketones 4a‒k, 6a‒f with ylidenemalononitrile 3 in the presence of sodium alkoxide. Meanwhile, nucleophilic attack of amines on 2-bromonicotinonitrile 9 (obtained through reaction of propenone 8 with malononitrile, followed by bromination with bromine in acetic acid) afforded 3-pyridinecarbonitriles 11a‒d. Single crystal X-ray of compound 7i reveals the monoclinic space group C2/c with 8 molecules per unit cell. Optimized structure of 7i [DFT/B3LYP, 6-31G(d,p)] shows close correlations to that of X-ray study. Compound 5l seems superior among all the synthesized analogues exhibiting bronchodilation properties about three folds potency compared to theophylline (standard reference) through pre-contracted tracheal rings with histamine standard method. Also compound 5a reveals promising observations (about two folds potency of the standard reference). Molecular modeling studies (3D-pharmacophore and 2D-QSAR) supported the observed biological properties.

Original languageEnglish (US)
Pages (from-to)920-931
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume138
DOIs
StatePublished - Jan 1 2017

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Molecular modeling
X-Rays
Bromine
X rays
Quantitative Structure-Activity Relationship
Halogenation
Theophylline
Ketones
Discrete Fourier transforms
Acetic Acid
Histamine
Amines
Sodium
Single crystals
Molecules

Keywords

  • Bronchodilation
  • Nicotinonitrile
  • Pharmacophore
  • QSAR

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Synthesis, molecular modeling studies and bronchodilation properties of nicotinonitrile containing-compounds. / Soliman, E. A.; Panda, Siva Shankar; Aziz, Marian N.; Shalaby, El Sayed M.; Mishriky, Nawal; Asaad, Fahmy M.; Girgis, Adel S.

In: European Journal of Medicinal Chemistry, Vol. 138, 01.01.2017, p. 920-931.

Research output: Contribution to journalArticle

Soliman, E. A. ; Panda, Siva Shankar ; Aziz, Marian N. ; Shalaby, El Sayed M. ; Mishriky, Nawal ; Asaad, Fahmy M. ; Girgis, Adel S. / Synthesis, molecular modeling studies and bronchodilation properties of nicotinonitrile containing-compounds. In: European Journal of Medicinal Chemistry. 2017 ; Vol. 138. pp. 920-931.
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