1,2-disubstituted indole, azaindole and benzimidazole derivatives possessing amine moiety: a novel series of thrombin inhibitors

Takeuchi, Kumiko; Bastian, Jolie A.; Gifford‐Moore, Donetta S.; Harper, Richard W.; Miller, Shawn C.; Mullaney, Jeffrey T.; Sall, Daniel J.; Smith, Gary; Zhang, Minsheng; Fisher, M.

doi:10.1016/s0960-894x(00)00454-6

Cited by 35 publications

(3 citation statements)

References 6 publications

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“…The following methods are available for the synthesis of 1,2disubstituted benzimidazoles: (I-II) aldehyde reacts with ophenylenediamines or N-alkyl-1,2-diaminobenzene, (III) N-alkylation of 2-substituted benzimidazoles, (IV) cyclocondensation of N-alkyl-N-acyl-1,2-diaminobenzene, (V) Suzuki coupling between aryl boronic acids and 1-halo-2-alkylbenzimidazoles and (VI-VII) transition metal-catalyzed amidation of o-halo Nalkylated anilines and aryl-amination of (o-bromo/ iodophenyl)amidines. [13][14][15][16][17] Similarly, there are numerous strat-egies to create quinazolinones: (I-III) oxidative condensation of o-aminobenzamides, 2-nitrobenzamides or isatoic anhydride with aryl aldehydes, (IV) 2-aminobenzamide with ketoalkynes, (V) condensation of anthranilic acid with formamide, (VI) Ullmann-type coupling of amines with 2-bromobenzamides, (VII) o-carboxamidation of N-arylamidines and (VIII) reaction between 2-halobenzonitriles and amides. [12,[18][19][20][21] The fundamental challenge in all these synthetic procedures is control of selectivity.…”

Section: Introductionmentioning

confidence: 99%

Solvent‐Free Synthesis of Substituted Benzimidazoles and Quinazolinones via Acceptorless Dehydrogenative Coupling Using Ferrocene‐Hydrazone‐Based Ru(II)‐p–cymene Catalysts

Yadav

Tamizh

et al. 2023

Asian J Org Chem

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A series of ferrocene‐hydrazone based Ru(II)‐p‐cymene complexes were investigated for their catalytic activity towards acceptorless dehydrogenative coupling (ADC) reactions. Ru(II)‐p‐cymene isonicotinic Fc‐hyrazone complex performed better in the solvent‐free synthesis of 1,2‐disubstituted benzimidazoles (up to 88%) and quinazolinones (up to 95%). The catalysis was extended to a wide range of benzylic alcohols. The synthesis of 1,2‐disubstituted benzimidazoles was accomplished with electron‐donating/‐withdrawing o‐phenylenediamines as well. A catalytic structure‐activity relationship was established by varying the steric and electronic parameters on the substrates. All the catalytic experiments exhibited good to moderate yields, with hydrogen and water as the only by‐products. The prepared complexes were well characterized using analytical and spectroscopic techniques. The molecular structures of the ligands and complex were resolved using single crystal X‐ray crystallographic studies.

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Section: Introductionmentioning

confidence: 99%

Solvent‐Free Synthesis of Substituted Benzimidazoles and Quinazolinones via Acceptorless Dehydrogenative Coupling Using Ferrocene‐Hydrazone‐Based Ru(II)‐p–cymene Catalysts

Yadav

Tamizh

et al. 2023

Asian J Org Chem

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“…Benzimidazole is well known for its promising pharmacological and biological activities such as antidiabetic, antimicrobial, antiviral, antitumor, antidepressant, antihistaminic, antioxidant, antihypertensive, anti-HIV, anticoagulant, antiallergic, and antihelmentic activities. − A range of pharmaceutically important marketed drugs are based on the benzimidazole scaffold (Figure ). Anthelmintic drugs including albendazole, mebendazole, triclabendazole, etc.…”

Section: Introductionmentioning

confidence: 99%

Substituted Benzimidazole Analogues as Potential α-Amylase Inhibitors and Radical Scavengers

et al. 2021

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Benzimidazole scaffolds are known to have a diverse range of biological activities and found to be antidiabetic and antioxidant. In this study, a variety of arylated benzimidazoles 1–31 were synthesized. Except for compounds 1, 6, 7, and 8, all are new derivatives. All compounds were screened for α-amylase inhibitory, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities. In vitro screening results revealed that all molecules demonstrated significant α-amylase inhibition with IC50 values of 1.86 ± 0.08 to 3.16 ± 0.31 μM as compared to standard acarbose (IC50 = 1.46 ± 0.26 μM). However, compounds showed significant ABTS and DPPH radical scavenging potentials with IC50 values in the range of 1.37 ± 0.21 to 4.00 ± 0.10 μM for ABTS and 1.36 ± 0.09 to 3.60 ± 0.20 μM for DPPH radical scavenging activities when compared to ascorbic acid with IC50 values of 0.72 ± 0.21 and 0.73 ± 0.05 μM for ABTS and DPPH radical scavenging potentials, respectively. Structure–activity relationship (SAR) was established after critical analysis of varying substitution effects on α-amylase inhibitory and radical scavenging (ABTS and DPPH) potentials. However, molecular docking was also performed to figure out the active participation of different groups of synthetic molecules during binding with the active pocket of the α-amylase enzyme.

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“…The first is the respective substitution on the C-1 or N-2 position of the preformed benzimidazoles, (i) N-alkylation of 2-substituted benzimidazoles (Ramla et al, 2007;Martin et al, 2015) and (ii) Suzuki coupling of aryl boronic acids with 1-halo-2-alkylbenzimidazoles (Wang and Smith, 2003;Martin et al, 2015). Another approach is the classic cyclocondensation of (iii) N-alkyl-N-acyl-1,2-diaminobenzene (Smith and Krchnák, 1999;Takeuchi et al, 2000) or (iv) N-alkyl-1,2-diaminobenzene with aldehyde (Smith and Krchnák, 1999;Özden et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Iron-Catalyzed Acceptorless Dehydrogenative Coupling of Alcohols With Aromatic Diamines: Selective Synthesis of 1,2-Disubstituted Benzimidazoles

et al. 2020

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Benzimidazoles are important N-heteroaromatic compounds with various biological activities and pharmacological applications. Herein, we present the first iron-catalyzed selective synthesis of 1,2-disubstituted benzimidazoles via acceptorless dehydrogenative coupling of primary alcohols with aromatic diamines. The tricarbonyl (η 4-cyclopentadienone) iron complex catalyzed dehydrogenative cyclization, releasing water and hydrogen gas as by-products. The earth abundance and low toxicity of iron metal enable the provision of an eco-friendly and efficient catalytic method for the synthesis of benzimidazoles.

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1,2-disubstituted indole, azaindole and benzimidazole derivatives possessing amine moiety: a novel series of thrombin inhibitors

Cited by 35 publications

References 6 publications

Solvent‐Free Synthesis of Substituted Benzimidazoles and Quinazolinones via Acceptorless Dehydrogenative Coupling Using Ferrocene‐Hydrazone‐Based Ru(II)‐p–cymene Catalysts

Solvent‐Free Synthesis of Substituted Benzimidazoles and Quinazolinones via Acceptorless Dehydrogenative Coupling Using Ferrocene‐Hydrazone‐Based Ru(II)‐p–cymene Catalysts

Substituted Benzimidazole Analogues as Potential α-Amylase Inhibitors and Radical Scavengers

Iron-Catalyzed Acceptorless Dehydrogenative Coupling of Alcohols With Aromatic Diamines: Selective Synthesis of 1,2-Disubstituted Benzimidazoles

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