Stereoselective synthesis of 3,4‐dihydropyrrolo[1,2‐a]pyrazin‐1(2H)‐one derivatives as PIM kinase inhibitors inspired from marine alkaloids

Casuscelli, F.; Ardini, Elena; Avanzi, Nilla; Badari, Alessandra; Casale, Elena; Disingrini, Teresa; Donati, Daniele; Ermoli, Antonella; Felder, E.; Galvani, Arturo; Isacchi, Antonella; Menichincheri, Maria; Montemartini, Marisa; Orrenius, Christian; Piutti, Claudia; Salom, Barbara; Papeo, Gianluca

doi:10.1002/chir.23501

Cited by 3 publications

(3 citation statements)

References 52 publications

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“…Although the bioavailability has improved, it may come at the cost of sacrificing some of the inhibitory potency against PIM enzymes (Figure 12A). 139 Furthermore, 112 (Usnic acid) is a metabolite extracted from lichen that possesses distinct anticancer properties due to its distinctive dibenzofuran scaffold. In order to enhance its therapeutic potential, flavonoids were incorporated into the structure of 112, which led to the synthesis of 113.…”

Section: Other Multitarget Inhibitorsmentioning

confidence: 99%

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Comprehensive Insights that Targeting PIM for Cancer Therapy: Prospects and Obstacles

Chen,

Mao,

Ren

et al. 2024

J. Med. Chem.

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Proviral integration sitea for Moloney-murine leukemia virus (PIM) kinases are a family of highly conserved serine/tyrosine kinases consisting of three members, PIM-1, PIM-2, and PIM-3. These kinases regulate a wide range of substrates through phosphorylation and affect key cellular processes such as transcription, translation, proliferation, apoptosis, and energy metabolism. Several PIM inhibitors are currently undergoing clinical trials, such as a phase I clinical trial of Uzanserti (5) for the treatment of relapsed diffuse large B-cell lymphoma that has been completed. The current focus encompasses the structural and biological characterization of PIM, ongoing research progress on small-molecule inhibitors undergoing clinical trials, and evaluation analysis of persisting challenges in this field. Additionally, the design and discovery of small-molecule inhibitors targeting PIM in recent years have been explored, with a particular emphasis on medicinal chemistry, aiming to provide valuable insights for the future development of PIM inhibitors. ■ SIGNIFICANCEA concise summary of research in the field of PIM inhibition for cancer, with a focus on medicinal chemistry, is presented. An analysis of current compounds entering clinical trials highlights existing issues and provides viewpoints on potential solutions. Future prospects and recommendations for development are discussed, emphasizing the need for unique perspectives and analyses in medicinal chemistry to stimulate critical thinking, expand understanding, and advance research in this field.

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Section: Other Multitarget Inhibitorsmentioning

confidence: 99%

“…High protein binding can potentially lead to issues such as metabolism and drug interactions. Although the bioavailability has improved, it may come at the cost of sacrificing some of the inhibitory potency against PIM enzymes (Figure A) …”

Section: Pim Inhibitors In Publicationsmentioning

confidence: 99%

Comprehensive Insights that Targeting PIM for Cancer Therapy: Prospects and Obstacles

Chen,

Mao,

Ren

et al. 2024

J. Med. Chem.

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“…In 2022, Casuscelli et al described a structure-based scaffold decoration and a stereoselective approach to discover new PIM kinases inhibitors. The synthesis, structure-activity relationship studies, chiral analysis, and pharmacokinetic data of 3,4dihydropyrrolo[1,2-a]pyrazin-1(2H)-one derivatives revealed that compound ( 34) is an excellent Pim1 and Pim2 inhibitor (Casuscelli et al 2022).…”

Section: F) 34-dihydropyrrolo[12-a]pyrazin-1(2h)-one Derivativesmentioning

confidence: 99%

Pim Kinases Inhibitors and Pyrimidine-Based Anticancer Agents

Issa

Hammam

Sakr

et al. 2023

Al-Azhar Journal of Pharmaceutical Sciences

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Human phosphatidyl inositol mannoside kinases (Pim kinases) are important biological target for discovery of new anticancer agents. In addition, Pyrimidines have a good contribution as building blocks of many anticancer agents. Hence, a literature survey about Pim kinases inhibitors and pyrimidine-based anticancer agents have been achieved. In this survey, we introduced Pim kinase inhibitors under clinical assessment including imidazo[1,2-b]pyridazines, isatins, thiazolidine-2,4-diones, pyridinamines, and diaminopyrazoles. In addition, Pim kinase inhibitors under development were presented. These compounds include pyridine-quinolines, benzimidazoles indoles, cyano pyridines, pyridothieno [3,2-d]pyrimidin-4-ones, oxadiazole, and 3,4-dihydropyrrolo[1,2a]pyrazin-1(2H)-ones. Furthermore, different pyrimidine-based anticancer agents have been discussed.

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Synthesis, Biological Evaluation, DFT Calculations and Molecular Docking of 5-Arylidene-Thiazolidine-2,4-Dione Derivatives

Zine,

Krid,

Boulcina

et al. 2023

Polycyclic Aromatic Compounds

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Stereoselective synthesis of 3,4‐dihydropyrrolo[1,2‐a]pyrazin‐1(2H)‐one derivatives as PIM kinase inhibitors inspired from marine alkaloids

Cited by 3 publications

References 52 publications

Comprehensive Insights that Targeting PIM for Cancer Therapy: Prospects and Obstacles

Comprehensive Insights that Targeting PIM for Cancer Therapy: Prospects and Obstacles

Pim Kinases Inhibitors and Pyrimidine-Based Anticancer Agents

Synthesis, Biological Evaluation, DFT Calculations and Molecular Docking of 5-Arylidene-Thiazolidine-2,4-Dione Derivatives

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