Potential antidiabetic agents. Pyrazolo[3,4-b]pyridines

Hohn, Hans; Poláček, Ivo; Schulze., E.

doi:10.1021/jm00270a006

Cited by 42 publications

(19 citation statements)

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“…The mass spectra were recorded on a Joel SX‐102 (FAB) spectrometer (JEOL, Tokyo, Japan). Phthalimidooxy ethyl bromide was synthesized by reported method, and 5‐methyl‐2,4‐dihyro‐3 H ‐pyrazol‐3‐one ( 1 ) were synthesis by literature method . Synthesized compounds were confirmed by elemental, spectral studies (IR, NMR, and mass), and chemical tests.…”

Section: Methodsmentioning

confidence: 99%

One‐pot Synthesis of Bis[1‐N,7‐N‐diethoxyphthalimido‐4,4′‐{3,5‐dimethyl‐4‐(4‐N,N‐dimethyl Aminophenyl)‐4,7‐dihydro‐1H‐dipyrazolo[3,4‐b;4′,3′‐e]Pyridin‐8‐yl}‐phenyl] Compounds and Their Antiviral Evaluation Against Cytomegalovirus (CMV) and Varicella‐zoster Virus (VZV) in Human Embryonic Lung (HEL) Cells

Hussain¹,

Ahmed²,

Khan³

et al. 2016

Journal of Heterocyclic Chem

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A one‐pot three components synthesis of substituted bis[1‐N,7‐N‐diethoxyphthalimido‐4,4′‐{3,5‐dimethyl‐4‐(4‐N,N‐dimethylaminophenyl)‐4,7‐dihydro‐1H‐dipyrazolo[3,4‐b;4′,3′‐e] pyridin‐8‐yl}‐phenyl] in moderate to high yields has been achieved by a two‐step reaction. All the synthesized compounds evaluate against cytomegalovirus and varicella‐zoster virus in human embryonic lung cells.

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Section: Methodsmentioning

confidence: 99%

One‐pot Synthesis of Bis[1‐N,7‐N‐diethoxyphthalimido‐4,4′‐{3,5‐dimethyl‐4‐(4‐N,N‐dimethyl Aminophenyl)‐4,7‐dihydro‐1H‐dipyrazolo[3,4‐b;4′,3′‐e]Pyridin‐8‐yl}‐phenyl] Compounds and Their Antiviral Evaluation Against Cytomegalovirus (CMV) and Varicella‐zoster Virus (VZV) in Human Embryonic Lung (HEL) Cells

Hussain¹,

Ahmed²,

Khan³

et al. 2016

Journal of Heterocyclic Chem

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“…The newly synthesized compounds were characterized by IR and NMR spectra, and the others were identified by comparison of their IR and physical properties with those of authentic samples [19,20]. 13 …”

Section: Methodsmentioning

confidence: 99%

“…Among solid acids, Al (HSO 4 ) 3 is a useful alternative to nitric acid as oxidant. The pyrazolopyridine ring system represents the core skeleton of a number of pharmaceutically important heterocyclic compounds possessing a broad range of biological activity, in particular potent cyclin kinase 1 (CDK1) inhibitors [1], HIV reverse transcriptase inhibitors [2], CCR1 antagonists [3], protein kinase inhibitors [4], inhibitors of cGMP degradation [5], xanthine oxidase inhibitors [6], and antiviral [7], antimalarial [8], vasodilator [9], antimicrobial [10], anti-inflammatory [11], anxiolytic [12], hypoglycemic [13], and antitumor agents [14].…”

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confidence: 99%

Aluminum hydrogen sulfate as a green catalyst for the solvent-free synthesis of pyrazolopyridines

Nikpassand

Fekri

2015

Russ J Gen Chem

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Aluminum hydrogen sulfate turned out to be a mild, convenient, and efficient reagent for the conversion of substituted benzyl alcohols into pyrazolopyridines via condensation with 3-methyl-1H-pyrazole-5-amine and CH acid (malononitrile or indan-1,3-dione) at room temperature under solvent-free conditions with high yield, high purity, and short reaction time.Keywords: pyrazolopyridine, solvent free, aluminum hydrogen sulfate, green catalyst 1 The text was submitted by the authors in English.The use of solid acids in organic reactions is important since solid acids have many advantages such as simplicity in handling, decreased reactor and plant corrosion problems, and more environmentally safe disposal. On the other hand, any reduction in the amount of liquid acid is required for economic and environmental protection. Among solid acids, Al (HSO 4 ) 3 is a useful alternative to nitric acid as oxidant. The pyrazolopyridine ring system represents the core skeleton of a number of pharmaceutically important heterocyclic compounds possessing a broad range of biological activity, in particular potent cyclin kinase 1CDK1) inhibitors [1], HIV reverse transcriptase inhibitors [2], CCR1 antagonists [3], protein kinase inhibitors [4], inhibitors of cGMP degradation [5], xanthine oxidase inhibitors [6], and antiviral [7], antimalarial [8], vasodilator [9], antimicrobial [10], anti-inflammatory [11], anxiolytic [12], hypoglycemic [13], and antitumor agents [14].In continuation of our ongoing studies on the synthesis of heterocyclic and pharmaceutical compounds using mild and practical protocols [15][16][17][18], herein we report our experimental results on the synthesis of Al (HSO 4 ) 3 and its application as a green oxidizing catalyst for the synthesis of pyrazolopyridines from different substituted benzyl alcohols, malononitrile or indan-1,3-dione, and 3-methyl-1H-pyrazol-5-amine under solvent-free condition (Scheme 1). To the best of our knowledge, there has been no report on the synthesis of pyrazolopyridine based on alcohols.With the catalyst in hand (see Experimental), we moved to study the effect of the catalyst amount on the model reaction of 4-nitrobenzyl alcohol (Ia) with malononitrile (II) and 3-methyl-1H-pyrazol-5-amine (IV). No reaction occurred in the absence of Al(HSO 4 ) 3 even after extending the reaction time, whereas 10 mol % of Al(HSO 4 ) 3 was sufficient to push the reaction forward; lower or higher amount of the catalyst did not improve the yield of pyrazolopyridine Va. The effect of various solvents on the transformation of Ia into Va in the presence of Al(HSO 4 ) 3 (10 mol %) was studied. Acetonitrile, n-hexane, ethanol, chloroform, and acetone, as well as solvent-free conditions, were tested

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“…[8][9][10][11] Compounds 27a, d-e, g-i, p, x, and z were commercially available. The other 1-methylpyrazoles, 27c and 27f, were prepared by condensation of methylhydrazine to the corresponding Michael acceptors 33 and 34, respectively.…”

Section: Chemistrymentioning

confidence: 99%

Discovery of New Orally Active Phosphodiesterase (PDE4) Inhibitors

Ochiai

Ishida

Ohtani

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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Phosphodiesterase 4 (PDE4) is an enzyme that is responsible for the inactivation of cyclic adenosine monophosphate (cAMP).1,2) The anti-inflammatory effects of PDE4 inhibitors have been well established in a variety of animal models. 3)However, clinical use of these inhibitors has not been achieved yet because of dose-limiting side effects such as nausea and vomiting that restrict therapeutic application. 4)In previous reports, we have described the design and synthesis of bicyclo[3 · 3 · 0]octane derivatives 5) and piperidine derivatives, 6) which are interesting new classes of PDE4 inhibitors with therapeutic potential. Structure activity relationship (SAR) studies of PDE4 inhibitors based on the structural features of Ariflo 1 7) have revealed that its further modification yields a series of PDE4 inhibitors with an improved therapeutic index relative to the classical inhibitor, rolipram 2 (Fig. 1). To create efficient new PDE4 inhibitors with a higher therapeutic potential, discovery and evaluation of a new chemical lead with a completely different structure was considered to provide another approach to chemical modification. Here we report on the discovery of two new orally active pyrazolopyridines 5 and 9 (Fig. 2). SAR data are also presented. ChemistryThe synthesis of the test compounds listed in Tables 1-3 is outlined in Chart 1. [8][9][10][11] Compounds 27a, d-e, g-i, p, x, and z were commercially available. The other 1-methylpyrazoles, 27c and 27f, were prepared by condensation of methylhydrazine to the corresponding Michael acceptors 33 and 34, respectively. 3-Methylpyrazoles, 27j-o, q-w, and y were prepared from 35 and the corresponding hydrazine derivatives. Michael addition of 27a-z to diethyl ethoxymethylenemalonate gave 28a-z, respectively, after which ring closure was accomplished with phosphorus oxychloride under reflux to afford chlorides 29a-z, respectively. Alkaline hydrolysis of 29a-z gave carboxylic acids 30a-z, respectively. Heating of 30a-z with thionyl chloride, followed by treatment with aqueous ammonia, resulted in production of the amides 31a-z, respectively. Replacement of the chloro moiety of 31a-z with appropriate anilines led to the test compounds 5 and 8-26. N-Methylation of the 3-methoxyaniline moiety afforded 7. Compounds 3, 4, and 6 were prepared from 31a according to the procedure described for preparation of 5 from 31a. Results and DiscussionA series of pyrazolopyridine derivatives were synthesized and evaluated for inhibition of phosphodiesterase type 4 prepared from U937 cells, 12) which were derived from human monocytes. The results of the assays are expressed as IC 50 values, i.e., the test compound concentration that achieved 50% inhibition relative to the vehicle. Test compounds were also evaluated for inhibition of LPS-induced production of tumor necrosis factor-a (TNF-a) in rats.13) The results are expressed as ID 50 values, i.e., the dose that showed 50% inhibition relative to the vehicle.During the course of screening of PDE4 inhibitors, compound 3 showed moderate ...

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Potential antidiabetic agents. Pyrazolo[3,4-b]pyridines

Cited by 42 publications

References 4 publications

Aluminum hydrogen sulfate as a green catalyst for the solvent-free synthesis of pyrazolopyridines

Discovery of New Orally Active Phosphodiesterase (PDE4) Inhibitors

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