New 2,6,9-trisubstituted purine derivatives as Bcr-Abl and Btk inhibitors and as promising agents against leukemia

Bertrand, Jeanluc; Dostálová, Hana; Kryštof, Vladimı́r; Jorda, Radek; Castro, Alejandro Palma; Mella, Jaime; Espinosa‐Bustos, Christian; Zárate, Alejandro; Salas, Cristian O.

doi:10.1016/j.bioorg.2019.103361

Cited by 16 publications

(24 citation statements)

References 43 publications

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“…To optimize the reaction conditions, 6-(2-benzylidenehydrazinyl)-9-butyl purine (1a) was selected as a model substrate which was prepared from 9-butyl-6-hydrazinyl purine [12][13][14] and the results were shown in Table 1. First, various common oxidants such as I 2 , OXONE, DTBP, TBHP, K 2 S 2 O 8 were tested (entry 1-6, Table 1).…”

Section: Resultsmentioning

confidence: 99%

A facile approach to [1,2,4]triazolo[3,4‐i]purine via PIDA oxidation ring‐closing reaction

Sun

et al. 2021

Journal of Heterocyclic Chem

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Section: Resultsmentioning

confidence: 99%

A facile approach to [1,2,4]triazolo[3,4‐i]purine via PIDA oxidation ring‐closing reaction

Sun

et al. 2021

Journal of Heterocyclic Chem

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“…Drugs, such as imatinib, nilotinib (4), and ponatinib (5), are known to target Bcr-Abl, while ibrutinib targets the BTK pathway (please see Reference [66] for a review of Bcr-Abl inhibitors and Reference [67] for a review of anticancer drugs targeting BTK). Bertrand et al synthesized 2,6,9-trisubstituted purine derivatives as candidate dual Bcr-Abl/Btk inhibitors [68]. Most of the target compounds synthesized displayed IC 50 values below 4 µM against Abl and Btk.…”

Section: Src Family Kinase (Sfk) Inhibitorsmentioning

confidence: 99%

Imidazoles as Potential Anticancer Agents: An Update on Recent Studies

et al. 2021

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Nitrogen-containing heterocyclic rings are common structural components of marketed drugs. Among these heterocycles, imidazole/fused imidazole rings are present in a wide range of bioactive compounds. The unique properties of such structures, including high polarity and the ability to participate in hydrogen bonding and coordination chemistry, allow them to interact with a wide range of biomolecules, and imidazole-/fused imidazole-containing compounds are reported to have a broad spectrum of biological activities. This review summarizes recent reports of imidazole/fused imidazole derivatives as anticancer agents appearing in the peer-reviewed literature from 2018 through 2020. Such molecules have been shown to modulate various targets, including microtubules, tyrosine and serine-threonine kinases, histone deacetylases, p53-Murine Double Minute 2 (MDM2) protein, poly (ADP-ribose) polymerase (PARP), G-quadraplexes, and other targets. Imidazole-containing compounds that display anticancer activity by unknown/undefined mechanisms are also described, as well as key features of structure-activity relationships. This review is intended to provide an overview of recent advances in imidazole-based anticancer drug discovery and development, as well as inspire the design and synthesis of new anticancer molecules.

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“…In addition, the purine ring is present in ATP, GTP, cyclic AMP, which display several functions in the signaling pathway in living organisms [2,4]. Because of that, purine scaffold is a building block that has been widely explored for drug development through decorating with different substituents to yield compounds with pharmacological properties [5–10]. That is the reason why some purine analogues have been approved for their clinical application as chemotherapeutic agents (antiviral, antiprotozoal, antifungal, and anticancer agents) and pharmacodynamic drugs (coronary vasodilator) [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…According to the aforementioned, in the last decades, several synthetic procedures to obtain di‐ or trisubstituted purines have been reported, where the positions C‐2, C‐6, and N‐9 are the most explored. The influences of different substituents in these positions in several bioactive purine derivatives have been extensively studied, and according to these results, optimal substituents have been identified [6,7,14–16]. An alkylated side chain at C‐2 position certainly opens the path to a significant range of possible modifications of the parent purines.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, since the purine heterocycle scaffold is an interesting option to obtain new antitumor compounds and continuing our program to develop 2,6,9‐trisubstituted purines with anticancer properties [5–7,25]; in this work, we reported the design of a family of purine derivatives bearing a new moiety linked at C‐2. In the design of our compounds, we considered our previous results and the chemical structures of certain antitumoral compounds (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Convergent synthesis, drug target prediction, and docking studies of new 2,6,9‐trisubstituted purine derivatives

Villegas

Satheeshkumar

Ballesteros-Casallas

et al. 2021

Journal of Heterocyclic Chem

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A set of new 2,6,9‐trisubstituted purine derivatives were designed and synthesized from 6‐chloro‐2‐fluoro‐9‐alkyl‐9H‐purine as the key starting material. These purines were synthesized via a multistep protocol and finally subjected to SNAr with various aminopiperidinyl salts. The structures of these compounds were established by substantiating them through spectral techniques like FT‐IR, 1H‐NMR, 13C‐NMR, and 19F‐NMR. In addition, for two purine derivatives, a reverse screening strategy based on ligand similarity (PharmMapper web server) resulted in a set of predicted protein target candidates. Interestingly, for both purines, the main potential target candidates belonged to key proteins involved within signaling pathways that are related to proliferation or survival of cancer cells. These proteins correspond mainly to enzymes and specifically kinases. To check if our purines could be ligands for two kinases involved in cancer, docking studies were performed. The results indicated that these purines fitted in the same cavity of crystalized inhibitors. Therefore, in this work we are developed new purine derivatives that could be good inhibitors of some kinases.

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New 2,6,9-trisubstituted purine derivatives as Bcr-Abl and Btk inhibitors and as promising agents against leukemia

Cited by 16 publications

References 43 publications

A facile approach to [1,2,4]triazolo[3,4‐i]purine via PIDA oxidation ring‐closing reaction

A facile approach to [1,2,4]triazolo[3,4‐i]purine via PIDA oxidation ring‐closing reaction

Imidazoles as Potential Anticancer Agents: An Update on Recent Studies

Convergent synthesis, drug target prediction, and docking studies of new 2,6,9‐trisubstituted purine derivatives

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