Novel 3-(1H-indol-3-yl)-2-[3-(4-methoxyphenyl)ureido]propanamides as selective agonists of human formyl-peptide receptor 2

Enza Lacivita, Igor A. Schepetkin, Madia L. Stama, Liliya N. Kirpotina, Nicola A. Colabufo, Roberto Perrone, Andrey Ivanovich Khlebnikov, Mark T. Quinn, Marcello Leopoldo

Результат исследований: Материалы для журналаСтатья

7 Цитирования (Scopus)

Выдержка

N-Formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCRs) that play critical roles in inflammatory reactions, and FPR-specific interactions can possibly be used to facilitate the resolution of pathological inflammatory reactions. We here report the synthesis and biological evaluation of six pairs of chiral ureidopropanamido derivatives as potent and selective formyl peptide receptor-2 (FPR2) agonists that were designed starting from our lead agonist (S)-3-(1H-indol-3-yl)-2-[3-(4-methoxyphenyl)ureido]-N-[[1-(5-methoxy-2-pyridinyl)cyclohexyl]methyl]propanamide ((S)-9a). The new compounds were obtained in overall yields considerably higher than (S)-9a. Several of the new compounds showed agonist properties comparable to that of (S)-9a along with higher selectivity over FPR1. Molecular modeling was used to define chiral recognition by FPR2. In vitro metabolic stability of selected compounds was also assessed to obtain preliminary insight on drug-like properties of this class of compounds.

Язык оригиналаАнглийский
Страницы (с-по)3913-3924
Число страниц12
ЖурналBioorganic and Medicinal Chemistry
Том23
Номер выпуска14
DOI
СостояниеОпубликовано - 11 сен 2014

Отпечаток

Formyl Peptide Receptor
Molecular modeling
G-Protein-Coupled Receptors
Derivatives
human FPR2 protein
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Цитировать

Novel 3-(1H-indol-3-yl)-2-[3-(4-methoxyphenyl)ureido]propanamides as selective agonists of human formyl-peptide receptor 2. / Lacivita, Enza; Schepetkin, Igor A.; Stama, Madia L.; Kirpotina, Liliya N.; Colabufo, Nicola A.; Perrone, Roberto; Khlebnikov, Andrey Ivanovich; Quinn, Mark T.; Leopoldo, Marcello.

В: Bioorganic and Medicinal Chemistry, Том 23, № 14, 11.09.2014, стр. 3913-3924.

Результат исследований: Материалы для журналаСтатья

Lacivita, Enza ; Schepetkin, Igor A. ; Stama, Madia L. ; Kirpotina, Liliya N. ; Colabufo, Nicola A. ; Perrone, Roberto ; Khlebnikov, Andrey Ivanovich ; Quinn, Mark T. ; Leopoldo, Marcello. / Novel 3-(1H-indol-3-yl)-2-[3-(4-methoxyphenyl)ureido]propanamides as selective agonists of human formyl-peptide receptor 2. В: Bioorganic and Medicinal Chemistry. 2014 ; Том 23, № 14. стр. 3913-3924.
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AU - Schepetkin, Igor A.

AU - Stama, Madia L.

AU - Kirpotina, Liliya N.

AU - Colabufo, Nicola A.

AU - Perrone, Roberto

AU - Khlebnikov, Andrey Ivanovich

AU - Quinn, Mark T.

AU - Leopoldo, Marcello

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KW - Chiral agonist

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KW - Metabolic stability

KW - Neutrophil

KW - Ureidopropanamide

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