One-Pot Synthesis of Densely Substituted Pyrazolo[3,4-<i>b</i>]-4,7-dihydropyridines

Rao, H. Surya Prakash; Adigopula, Lakshmi Narayana; Krishna, Rajamani

doi:10.1021/acscombsci.6b00156

Cited by 14 publications

(3 citation statements)

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“…The large number of synthetic routes to pyrazolo[3,4- b ]pyridines and their applications brings great interest in this area. The most commonly applied method for the preparation of pyrazolo[3,4- b ]pyridines uses 5-aminopyrazole as synthetic precursor [ 36 – 39 ]. Regardless to substantial studies in this field, researchers are still focused to provide convenient regioselective synthetic methods with mild conditions and good yields of the reactions [ 40 – 41 ].…”

Section: Reviewmentioning

confidence: 99%

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

Aggarwal

Kumar

2018

Beilstein J. Org. Chem.

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The condensation of 5-aminopyrazole with various bielectrophilic moieties results in the formation of pyrazoloazines, an interesting array of fused heterocyclic systems. The development of new synthetic routes towards pyrazoloazines for their biological and medicinal exploration is an attractive area for researchers throughout the world. The present review focuses on various synthetic methods developed in the last decade for the synthesis of differently substituted pyrazoloazines by a broad range of organic reactions by means of 5-aminopyrazole as a precursor. ReviewPyrazole and its derivatives are known to exhibit significant biological and pharmacological activities such as: anticancer [1,2], anti-inflammatory [3,4], antioxidant [5], antibacterial [6][7][8], analgesic [9], antiviral [10,11], antimicrobial [12,13], antifungal [6], antiglycemic [14], antiamoebic [15] and antidepressive [16,17]. Considering the immense biological properties pyrazole is one of the most widely studied nitrogen-containing heterocyclic nuclei. Fused pyrazole derivatives are composed of the pyrazole nucleus attached to other heterocyclic moieties which enable them to exhibit improved pharmacological activities compared to the isolated fragments. These compounds are currently used in several marketed drugs like cartazolate (1), zaleplon (2), sildenafil (3), allopurinol (4), indiplon (5), etazolate (6) etc. (Figure 1). Fused pyrazole derivatives, especially pyrazoloazines have been reported to mimic purine bases, present in DNA and RNA, due to close structural resemblance.In addition to the immense biological potential related to fused pyrazoles, their synthetic potential needs to be reviewed for further improvements and extension of interests. Various efforts have been developed for the synthesis of pyrazole-based fused heterocycles. 5-Aminopyrazoles have been extensively employed as useful synthons in designing and constructing a Beilstein J. Org. Chem. 2018, 14, 203-242. 204 A number of review articles have been published by us and others highlighting the synthetic and biological aspects of 5-aminopyrazoles [26][27][28] as well as on the synthesis of fused pyrazole derivatives [25]. However, a perusal of literature reveals that the importance of 5-aminopyrazoles as synthetic precursors for fused heterocycles has not been reported till now to the best of our knowledge. Recent literature shows resurgence of interest in the chemistry and bioactivity of 5-aminopyrazole derivatives leading to improvements in several already known reactions and syntheses of various fused heterocyclic derivatives with various biological activities. Considering the synthetic importance of 5-aminopyrazoles and synthesis of fused pyrazole derivatives with the need for a more general collection, herein we report an exhaustive overview of the main developments in the last decade in the chemistry of 5-aminopyrazoles for the design and synthesis of fused pyrazoloazines.The typical reactivity of 5-aminopyrazoles 5-Aminopyrazoles are polyfunctional co...

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Section: Reviewmentioning

confidence: 99%

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

Aggarwal

Kumar

2018

Beilstein J. Org. Chem.

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“…23 We have previously reported that the condensation of 5-amino-3-phenylpyrazoles 11 with 4H-chromenes 12 in EtOH reflux provided dihydropyazolo [3,4-b]pyridines 13 (Equation 2, Scheme 1). 24 In this remarkable transformation, initially formed C-alkylated 4H-chromene rearranged to 13 via chromene ring opening followed by recyclization. Dehydrogenation of 13 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) provided pyrazolo [3,4-b]pyridines 14.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Molecular Docking and Biological Activity of Pyrazolo[3,4-b]pyridines as Promising Lead Candidates AgainstMycobacterium tuberculosis

Rao,

Gunasundari,

Adigopula

et al. 2023

Preprint

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Pyrazolo[3,4-b]pyridine is a medicinally privileged structure. We have achieved a new and facile synthesis of a combinatorial library of its tetra- and persubstituted derivatives by trifluoracetic acid catalysed condensation of a group of 5-aminopyrazoles and a group of alpha-oxoketene dithioacetals. Furthermore, we demonstrated structural modification of the products via reductive desulfurization, hydrolysis of the ester and Suzuki coupling of the bromo derivative with aryl bornoic acids. Some of the products were subjected to in vitro MABA assay against M. tuberclulosis H37Rv strain and in silico analysis by binding to pantothenate synthetase from M. tuberclulosis (MTBPS). The results indicated that the pyazolo[3,4-b]pyridine with N(1)CH3, C(3)C6H5, C(4) pCH3C6H5, C(5)CO2Et, C(6)SMe substitutions exhibits promising antituberculotic activity.

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“…Pyrazole is an interesting heterocycle to investigate. It has also gotten a lot of interest because it is being studied for a broad-spectrum biological property. − The 1,3,4-oxadiazole is being studied because of its potentially relevant pharmacological activity. − …”

Section: Introductionmentioning

confidence: 99%

Conventional and Microwave-Assisted Synthesis, Antitubercular Activity, and Molecular Docking Studies of Pyrazole and Oxadiazole Hybrids

et al. 2021

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Microwave-assisted organic reaction enhancement (MORE) has become more important in synthetic organic chemistry for efficient resource utilization. In this study, we synthesized bioactive compounds using both traditional and microwave methods. Microwave-assisted synthesis takes less time and produces higher yields and quality than conventional approaches. We reported the synthesis of N′-(1-(2-(3-(4chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazol-3(2H)yl)ethylidene) substituted hydrazides (4a−t). We also tested them against two strains: M. tuberculosis H 37 Ra and M. bovis BCG. Against M. tuberculosis H 37 Ra, the compounds 4e, 4h, 4k, 4p, and 4s were the most effective. Compounds 4f, 4g, and 4s showed significant activity against M. bovis BCG. The structures of newly synthesized molecules were determined using spectral methods. Furthermore, molecular docking investigations into the active site of mycobacterial InhA yielded well-clustered solutions for these compounds' binding modalities producing a binding affinity in the range of −10.366 to −8.037. Theoretical results were in good accord with the observed experimental values. The docking score of compound 4e was −10.366, and the Glide energy was −66.459 kcal/mol.

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One-Pot Synthesis of Densely Substituted Pyrazolo[3,4-b]-4,7-dihydropyridines

Cited by 14 publications

References 29 publications

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

Design, Synthesis, Molecular Docking and Biological Activity of Pyrazolo[3,4-b]pyridines as Promising Lead Candidates AgainstMycobacterium tuberculosis

Conventional and Microwave-Assisted Synthesis, Antitubercular Activity, and Molecular Docking Studies of Pyrazole and Oxadiazole Hybrids

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