Regioselective N1-alkylation of 3,4-dihydropyrimidine-2(1H)-ones: Screening of their biological activities against Ca2+-ATPase

Putatunda, Salil; Chakraborty, Srabasti; Ghosh, Swatilekha; Nandi, Pinki; Chakraborty, Supriya; Sen, Parimal C.; Chakraborty, Arijit

doi:10.1016/j.ejmech.2012.04.043

Cited by 21 publications

(7 citation statements)

References 26 publications

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“…Once the DHPMs are built, the regioselectivity is high and the reactions occur on N-3 instead of the less reactive N-1. In fact, a few publications can be found wherein DHPM N-1 alkylation was achieved; 28,29 however, no publications describing arylation at N-1 of the DHPM have been found. For this purpose, it appears that the best strategy is to link the aromatic moiety to nitrogen 1 before the Biginelli reaction.…”

Section: Chemistrymentioning

confidence: 99%

Effect of N-1 arylation of monastrol on kinesin Eg5 inhibition in glioma cell lines

et al. 2018

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An original and focused library of two sets of dihydropyrimidin-2-thiones (DHPMs) substituted with N-1 aryl groups derived from monastrol was designed and synthesized in order to discover a more effective Eg5 ligand than the template. Based on molecular docking studies, four ligands were selected to perform pharmacological investigations against two glioma cell lines. The results led to the discovery of two original compounds, called and, with an anti-proliferative effects, achieving IC values of about half that of the IC of monastrol in both cell lines. As with monastrol, flow cytometry analyses showed that the and compounds induced cell cycle arrest in the G/M phase, and immunocytochemistry essays revealed the formation of monopolar spindles due to Eg5 inhibition without any toxicity to .

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Section: Chemistrymentioning

confidence: 99%

Effect of N-1 arylation of monastrol on kinesin Eg5 inhibition in glioma cell lines

et al. 2018

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“…Synthetic methodologies so far described for derivatization of Biginelli products are largely dictated by the intrinsic reactivity of the 3,4-DHPM scaffold, addressing concerns of compatibility with the existing functionalities, namely, the multiple heteroatoms, an α,βunsaturated carbonyl moiety and a reaction-prone alkyl substituent on C6. Specifically, analogues have been reported, resulting from the following processes: N1 or N3 alkylation or acylation [20][21][22][23][24][25]; C6 alkyl substituent elaboration to a functionalized derivative [26,27]; and various intramolecular cyclizations (e.g., N1-C6, C2-N3, C4-C5, C4-C6, C5-C6) [24,26,[28][29][30] depending on the nature of substituents on each position.…”

Section: Introductionmentioning

confidence: 99%

N-Directed Pd-Catalyzed Photoredox-Mediated C–H Arylation for Accessing Phenyl-Extended Analogues of Biginelli/Suzuki-Derived Ethyl 4-Methyl-2,6-diphenylpyrimidine-5-carboxylates

2021

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The availability and application of direct, functional group-compatible C–H activation methods for late-stage modification of small-molecule bioactives and other valuable materials remains an ongoing challenge in organic synthesis. In the current study, we demonstrate that a LED-activated, photoredox-mediated, Pd(OAc)2-catalyzed C–H arylation, employing a phenyldiazonium aryl source and either tris(2,2′-bipyridine)ruthenium(II) or (2,2′-bipyridine)bis[3,5-di-fluoro-2-[5-(trifluoromethyl)-2-pyridinyl-kN][phenyl-kC]iridium(III) as photoredox initiator, may successfully produce unprecedented mono- and bis-phenyl derivatives of functionality-rich 2,6-diphenylpyrimidine substrates at room temperature. The series of 19 substrates employed herein, which share the biologically-relevant 4-methyl-2,6-diphenylpyrimidine-5-carboxylate scaffold, were generated via a synthetic route involving (3-component) Biginelli condensation, oxidative dehydrogenation of the obtained 3,4-dihydropyrimidin-2(1H)-one to 2-hydroxypyrimidine, O-sulfonylation, and Suzuki-Miyaura C–C cross-coupling. Submission of these substrates to pyrimidine-N-atom-directed C–H arylation conditions led to regioselective phenylation at the ortho site(s) of the pyrimidine-C2-connected phenyl ring, revealing substituent-dependent electronic and steric effects. A focused library of 18 mono- and 10 bis-phenyl derivatives was generated. Its members exhibit interesting 3D and peripheral substitution features that render them promising for evaluation in drug discovery efforts.

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“…Different strategies have been used for the modification of 3,4-dihydropyrimidine-2(1H)-ones. For instance, N-alkylation is one of the most usable but other methods include mild base Cs 2 CO 3 , K 2 CO 3 (Putatunda et al, 2012), the Mitsunobu-type reaction (Dallinger & Kappe, 2002), or phase-transfer catalysis (Singh et al, 2009). Unfortunately, these strategies suffer from the disadvantage that the procedures need to be carried out in harsh conditions.…”

Section: Structure Descriptionmentioning

confidence: 99%

5-Acetyl-6-methyl-4-phenyl-1-(prop-2-ynyl)-3,4-dihydropyrimidin-2(1H)-one

Kaoukabi¹,

Taourirte²,

Lazrek³

et al. 2017

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The 4-dihydropyrimidin-2(1H)-one moiety of the title molecule, C16H16N2O2, displays a half-chair conformation. The least-squares mean plane through this heterocycle is almost perpendicular to the aromatic ring [dihedral angle = 89.52 (8)°] and to the prop-2-ynyl chain [C—C—N—C torsion angle of −73.2 (2)°]. The mean plane through the acetyl group makes a dihedral angle of 30.93 (10)° with the mean plane of the heterocycle. There is an intramolecular C—H...O hydrogen bond forming anS(6) ring motif. In the crystal, molecules are linked by pairs of N—H...O hydrogen bonds forming inversion dimers.

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Regioselective N1-alkylation of 3,4-dihydropyrimidine-2(1H)-ones: Screening of their biological activities against Ca2+-ATPase

Cited by 21 publications

References 26 publications

Effect of N-1 arylation of monastrol on kinesin Eg5 inhibition in glioma cell lines

Effect of N-1 arylation of monastrol on kinesin Eg5 inhibition in glioma cell lines

N-Directed Pd-Catalyzed Photoredox-Mediated C–H Arylation for Accessing Phenyl-Extended Analogues of Biginelli/Suzuki-Derived Ethyl 4-Methyl-2,6-diphenylpyrimidine-5-carboxylates

5-Acetyl-6-methyl-4-phenyl-1-(prop-2-ynyl)-3,4-dihydropyrimidin-2(1H)-one

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