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Synthesis 2024; 56(08): 1297-1308
DOI: 10.1055/a-2232-8113
paper

Synthesis of New 5- or 7-Substituted 3-Nitroimidazo[1,2-a]pyridine Derivatives Using SNAr and Palladium-Catalyzed Reactions To Explore Antiparasitic Structure–Activity Relationships

Romain Paoli-Lombardo
a   Aix Marseille Univ, CNRS, ICR UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, 13385 Marseille, France
,
Nicolas Primas∗
a   Aix Marseille Univ, CNRS, ICR UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, 13385 Marseille, France
b   AP-HM, Service Central de la Qualité et de l’Information Pharmaceutiques, 13005 Marseille, France
,
Sandra Bourgeade-Delmas
c   UMR 152 PHARMA-DEV, Université de Toulouse, IRD, UPS, 31062 Toulouse, France
,
Alix Sournia-Saquet
d   LCC-CNRS Université de Toulouse, CNRS, UPS, 31077 Toulouse, France
,
Caroline Castera-Ducros
a   Aix Marseille Univ, CNRS, ICR UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, 13385 Marseille, France
b   AP-HM, Service Central de la Qualité et de l’Information Pharmaceutiques, 13005 Marseille, France
,
Inès Jacquet
a   Aix Marseille Univ, CNRS, ICR UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, 13385 Marseille, France
,
Pierre Verhaeghe
d   LCC-CNRS Université de Toulouse, CNRS, UPS, 31077 Toulouse, France
e   Université Grenoble Alpes, CNRS, DPM UMR 5063, 38041 Grenoble, France
,
Pascal Rathelot
a   Aix Marseille Univ, CNRS, ICR UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, 13385 Marseille, France
b   AP-HM, Service Central de la Qualité et de l’Information Pharmaceutiques, 13005 Marseille, France
,
Patrice Vanelle∗
a   Aix Marseille Univ, CNRS, ICR UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, 13385 Marseille, France
b   AP-HM, Service Central de la Qualité et de l’Information Pharmaceutiques, 13005 Marseille, France
› Author AffiliationsThis research was funded by Aix-Marseille Université (AMU), the Centre National de la Recherche Scientifique (CNRS), and by Assistance Publique – Hôpitaux de Marseille (AP-HM).
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Abstract

Zoom Image
Figure 1 Structures of metronidazole and antikinetoplastid nitroheterocyclic drug compounds

To study the antikinetoplastid structure–activity relationships in a 3-nitroimidazo[1,2-a]pyridine series, we explored the substitution of positions 5 and 7 of the scaffold, developing nucleophilic aromatic substitution reactions and palladium-catalyzed Suzuki–Miyaura, Sonogashira, and Buchwald–Hartwig cross-coupling reactions that had never been reported at these positions in this series. In four steps from 2-amino(bromo)pyridines, 33 original compounds were obtained, allowing a better definition of the antiparasitic pharmacophore.

Key words

nitroaromatic compounds - imidazo[1,2-a]pyridines - kinetoplastids - nucleophilic aromatic substitution - palladium-catalyzed cross-coupling reactions - microwave irradiation

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2232-8113.
  • Supporting Information


Publication History

Received: 24 October 2023

Accepted after revision: 19 December 2023

Accepted Manuscript online:
19 December 2023

Article published online:
19 January 2024

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