Turn-on fluorescence sensor based on the aggregation of pyrazolo[3,4-b]pyridine-based coumarin chromophores induced by Hg

We developed a new fluorescent sensor (PPC-S) for Hg²⁺ based on the aggregation-induced emission (AIE) of pyrazolo[3,4-b]pyridine-based coumarin chromophore (PPC-O). Given the desulfurization reaction with Hg²⁺, AIE inactive PPC-S can be transformed into PPC-O with AIE activity, which can be employed for the fluorescence turn-on detection of Hg²⁺ with satisfactory selectivity and sensitivity in aqueous solutions.     

Synthesis of pyrazolo[3,4-b][1,4]diazepines and pyrazolo[3,4-b]pyrazines

The synthesis and structure elucidation of new pyrazolo[3,4-b][1,4]diazepines and pyrazolo[3,4-b]pyrazines are reported and the characterisation of isomers and tautomers by proton and carbon-13 nmr are discussed. In some case only NOE experiments allow us to identify the isomeric structure.     

Synthesis and alkylation of pyrazolo[3,4-c]isoquinolines and hexahydrocyclohepta[d]pyrazolo[3,4-b]pyridines

The condensation of 1-acyl-2-(morpholin-4-yl)cycloalkenes with 3-amino-1-phenyl-1H-pyrazol-5(4H)-ones gave the corresponding 2,3,6,7,8,9-hexahydropyrazolo[3,4-c]isoquinoline and 3,6,7,8,9,10-hexahydrocyclohepta[ d]pyrazolo[3,4-b]pyridine derivatives. Alkylation of 2,3,6,7,8,9-hexahydropyrazolo[3,4-c]-isoquinolines with alkyl halides occurred at the nitrogen atom in the 3-position. The structure of 7-methyl-2,5-diphenyl-2,3,6,7,8,9-hexahydro-1H-pyrazolo[3,4-c]isoquinolin-1-one was proved by X-ray analysis.     

Synthesis of 3-aryl-6H-isoxazolo[3,4-d]pyrazolo[3,4-b]pyridines and 3-aryl-6H-isoxazolo[5,4-d]pyrazolo[3,4-b]pyridines

The synthesis and characterization of a number of 3-aryl-6H-isoxazolo[3,4-d]pyrazolo[3,4-b]pyridines and 3-aryl-6H-isoxazolo[5,4-d]pyrazolo[3,4–6]pyridines from common precursors, 5-benzoyl-4-chloro-1H-pyrazolo-[3,4-b]pyridines, has been described. The structures were determined by unambiguous chemical synthesis and by isolation and ¹³C nmr analysis of some key, isolated, intermediates. The ability of these compounds to displace [3H]flunitrazepam from CNS binding sites was also observed.     

Synthesis of pyrazolo[3,4-c]isoquinoline and pyrazolo[3,4-b]pyridine derivatives from azomethines and CH-acidic compounds

Summary Donor substituted arylidene aminopyrazoles1a–c and CH-acidic 1,3-dicarbonyl compounds2a–e give in ethanol in an addition/cyclization reaction pyrazolo[3,4-c]isoquinolines4a–i and pyrazolo[3,4-b]pyridine derivatives5a,b, respectively. Using ethyl cyanoacetate as CH-acidic component, cinnamate6 and the cyano substituted pyrazolo[3,4-b]pyridine7 are formed.

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Synthese von Pyrazolo[3,4-c]isochinolin- und Pyrazolo[3,4-b]pyridin-Derivaten aus Azomethinen und CH-aciden Verbindungen

Zusammenfassung Die Reaktion der donorsubstituierten Aryliden-aminopyrazole1a–c mit den CH-aciden 1,3-Dicarbonylverbindungen2a–e führt in einer Additions/Cyclisierungsreaktion zu den Pyrazolo[3,4-c]isochinolin-4a–i bzw. Pyrazolo[3,4-b]pyridin-Derivaten5a,b. Verwendet man Cyanessigester als CH-acide Komponente, werden der Zimtsäureester6 und das cyanosubstituierte Pyrazolo[3,4-b]pyridin7 gebildet.

     

Synthesis of pyridazino[3,4-b]quinoxalines and pyrazolo[3,4-b]-quinoxaline by 1,3-dipolar cycloaddition reaction

The pyridazino[3,4-b]quinoxalines 6a,b and pyrazolo[3,4-b]quinoxaline hydrochloride 9 were synthesized by the 1,3-dipolar cycloaddition reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 5 with dimethyl or diethyl acetylenedicarboxylate and 2-chloroacrylonitrile, respectively. The reaction mechanisms were postulated for the formation of 6a,b and 9 .     

Study of the structures of indazoles,pyrazolo [3,4-b] pyridines,and pyrazolo[3,4-b]pyrazine by IR spectroscopy

It is shown on the basis of a study of the IR spectra of indazoles, pyrazolopyridines, and pyrazolopyrazine in the solid state and of their N-deutero-substituted derivatives and hydrochlorides at room temperature and at the temperature of liquid nitrogen that these heterocycles exist in a tautomeric form in which the labile hydrogen atom is localized on the nitrogen atom of the pyrazole ring. It was established that 6-aminopyrazolopyridine exists in the crystalline state in the amino form and that it is protonated at the ring nitrogen atom rather than at the amino group. The applicability of the temperature-shift method for the detection not only of NH bands but also of ND bands is demonstrated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 662–667, May, 1977.     

Synthesis of pyrido[3,4-b]pyrano[3,4-b]indoles

The synthesis of some pyrido[3,4-b]pyrano[3,4-b]indoles ( 3 ) from 3-hydroxy-4-(3-indolyl)piperidines ( 6 ) is reported.     

Synthesis of condensed tricyclic pyrazolo[3,4-b]thieno[2,3-d]pyridine and related isostere derivatives

In this paper we report the synthesis of an isosteric series of new heterotricyclic derivatives, corresponding to pyrazolo[3,4-b]thieno[2,3-d]pyridine ( 1 ), pyrazolo[3,4-b]furano[2,3-d]pyridine ( 2 ) and pyrazolo[3,4-b]pyrrolo[2,3-d]pyridine ( 3 ). These functionalized compounds were obtained, in high overall yield, by an ‘one-pot’ reaction of the chloroester intermediate 4 , possessing the pyrazolo[3,4-b]pyridine system, with an adequate α-hetero-acetyl ester derivative, in SNAr/Dieckman cyclization type consecutive reactions.     

Synthesis of enantiomerically pure perhydrofuro[3,4-b]pyrans and perhydrofuro[3,4-b]furans

Olefinic diols, prepared from (R)-(+)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde via olefination and hydrolysis, were converted into enantiomerically pure hydroxy substituted tetrahydrofuran derivatives by cyclization using N-phenylselenophthalimide and BF₃. The PhSe group in the C-4 position of these tetrahydrofurans was then substituted by an allyl group using allyltributylstannane in the presence of AIBN. The selenium promoted cyclizations of the allyl tetrahydrofurans in which the OH and the allyl groups are trans to each other formed the enantiopure perhydrofuro[3,4-b]pyrans, while the cyclization of the allyl tetrahydrofurans in which the OH and the allyl groups are cis gave rise to the perhydrofuro[3,4-b]furans. These bicyclic products were finally deselenenylated with triphenyltin hydride and AIBN.     

A convenient synthesis of novel pyridazino[3,4-b]quinoxaline and pyrazolo[3,4-b]quinoxaline utilizing 1,3-dipolar cycloaddition reaction

The reaction of 2,6-dichloroquinoxaline 4-oxide 4 with methylhydrazine gave 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 5, whose reaction with dimethyl acetylenedicarboxylate or 2-chloroacrylonitrile resulted in the 1,3-dipolar cycloaddition reaction to afford 7-chloro-3,4-bismethoxycarbonyl-1-methyl-1,2-dihydropyridazino[3,4-b]quinoxaline 6 or 6-chloro-3-hydroxymethylene-1-methyl-2,3-dihydro-1H-pyrazolo[3,4-b] quinoxaline hydrochloride 7, respectively.     

Fluorine-containing heterocycles: Part III. Synthesis of some new furo[2,3-b]-, pyrazolo[3,4-b]- and thieno[2,3-b]pyridines with anticipated biological activities

3-Cyano-6-(2-thienyl)-4-trifluoromethylpyridine-2(1H)-one (1) and its thiono analog 2 were prepared by the reaction of (2-thenoyl)-ω,ω,ω-trifluoroacetone with cyanoacetamide or cyanothioacetamide, respectively. Interaction of compound 1 with ethyl chloroacetate or chloroacetamide led to the regioselective formation of O-alkylated pyridines 3 and 10. The latter compounds underwent some successive reactions to furnish the promising furopyridines (4 and 7–9) and pyrazolopyridines (12–15). The reaction of 2 with chloroacetamides or chloroacetonitrile furnished 2-functionalized 3-amino-6-(2-thienyl)-4-trifluoromethyl-thieno[2,3-b]pyridines (16a, b) which were used as key intermediates in the synthesis of the title thienopyridines. Structures of the newly synthesized compounds were established on the basis of their elemental and spectral (IR, ¹H NMR and mass) analyses.     

Synthesis,structure, and properties of pyrazolo[4,3-b]quinuclidine derivatives

It was shown by means of ¹H and ¹³C NMR spectroscopy that the reaction of 2-arylmethylene-3-oxoquinuclidines with hydrazine hydrate gives 4a-hydroxy-7-aryl-4a,5,7,7a-tetrahydropyrazolo[4,3-b]quinuclidines, which are stable in the crystalline state but undergo dehydration to the corresponding 7-aryl-6H-7,7a-dihydropyrazolo[4,3-b]quinuclidines in solutions. The latter undergo cleavage to 3-(4-piperidyl)-5-arylpyrazoles when they are heated in an alkaline medium.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1248–1256, September, 1985.     

Synthesis of novel isoxazole functionalized pyrazolo[3,4-b]pyridine derivatives; their anticancer activity

A series of novel isoxazole functionalized pyrazolo[3,4-b]pyridine derivatives 5a-n were prepared, respectively, initiated from 6-thiophenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-3-amine 3 through selective N-propargylation, and these N-propargylated compounds 4 were cyclized with aryloximes by using of sodium hypochlorite, and obtained the title products 5a-n . All the final products 5a-n were submitted for anticancer activity against four cancer cell lines such as “HeLa—cervical cancer (CCL-2); COLO 205—colon cancer (CCL-222); HepG2—liver cancer (HB-8065); MCF7—breast cancer (HTB-22)”; Compounds 5c , 5d , and 5h are found to have more prominent anticancer activity at micro molar concentration.     

Synthesis of aromatic pyrazolo[4,5-b]pyridine derivatives

Cyclocondensation of chalcones with 5-amino-3-methyl-1-phenylpyrazole leads to the formation of 2,4-diaryl-5-methyl-7-phenyl-3,4-dihydropyrazolo-[4,5-b]pyridines, which undergo aromatization upon treatment with N-bromosuccinimide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1247–1251, September, 1987.     

Reactivity of pyrazolo[4,3-c][1,2,5]oxadiazin-3(5H)-ones toward C-nucleophiles: Synthesis of pyrazolo[3,4-b]pyrazines

The reaction of pyrazolo[4,3-c][1,2,5]oxadiazin-3(5H)-ones 1 with carbanions prepared in situ from compounds containing an activated methylene group afforded pyrazolo[3,4-b]pyrazines 4–13 in good yields. The possible reaction mechanism is proposed and discussed.     

Tautomerism phenomenon of pyrazolo[3,4-b]quinoline: spectroscopic and quantum mechanical studies

Tautomerism of pyrazolo[3,4-b]quinoline (PQ) was studied using electronic absorption and emission spectroscopies in various polar and nonpolar solvents. The absorption spectra of the tautomers were modeled, and the respective bands were assigned using ab initio quantum mechanical calculations. Temperature-dependent absorption spectra showed the dynamic equilibrium of the two species, which were observed only in aliphatic solvents. The anomalous relative populations of the tautomers were explained by the stabilizing effect of the specific PQ-hydrocarbon interactions. Excited-state intramolecular proton transfer (ESIPT) was proposed to explain the measured fluorescence spectra. Hydrogen bonds that are formed in methanol and benzene were shown to strongly influence the nature of both the absorption and emission spectra.     

Synthesis of dihydrothieno[3,4-b]indoles

A new heterocyclic system — 3-imino-4-methyldihydrothieno[3,4-b]indole — was obtained by treatment of 1-methylindole-2-carboxylic acid thioamide with aldehydes or ketones in the presence of hydrogen chloride. Reactions involving saponification and acetylation of the imino group of the thieno ring and opening of the thieno ring by the action of LiAlH₄ to give a bis(indolylphenylmethyl) sulfide were carried out. A scheme is proposed in which the SH group of the thioamide adds to the carbonyl compound in the first step, after which the product undergoes intramolecular cyclization in the 3 position of indole.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1327–1331, October, 1977.