Synthesis of pyrazolo[3,4‐<i>b</i>][1,4]diazepines and pyrazolo[3,4‐<i>b</i>]pyrazines

Colombo, Augusto; Frigola, Jordi; Pares, J.; Andaluz, Blas

doi:10.1002/jhet.5570260413

Cited by 14 publications

(5 citation statements)

References 4 publications

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“…Also, the compound 23 underwent a cyclocondensation reaction upon treatment with arylglyoxal in ethanol to afford the corresponding regioisomers 25a,b and 26a,b . When compound 23 was heated with arylpyruvic acids, 6‐aryl‐1‐phenyl‐3‐methyl‐5‐hydroxy‐ 1H ‐pyrazolo[3,4‐ b ] pyrazines (27a–d) were obtained (Scheme ) .…”

Section: Synthesis Of Pyrazolo[34‐b]pyrazine Starting With Pyrazole mentioning

confidence: 99%

A Concise Review on the Synthesis and Reactions of Pyrazolopyrazine Heterocycles

ul‐Malik

Zaki

El‐Dean

et al. 2018

Journal of Heterocyclic Chem

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The pyrazolopyrazine ring system is a very interesting class of heterocyclic compounds that were considered as important scaffolds of many efficacious biologically active agents that show anticancer with low toxicity, antioxidant, anticonvulsant, antiparasitic, anti‐inflammatory, antiviral, antibacterial, antifungal, and analgesic activities. This review throws light on the detailed synthetic approaches for the synthesis and reactions of pyrazolopyrazine moiety. This follow up may encourage the chemists to generate new routes possessing pyrazolopyrazine nucleus with high efficacy.

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Section: Synthesis Of Pyrazolo[34‐b]pyrazine Starting With Pyrazole mentioning

confidence: 99%

A Concise Review on the Synthesis and Reactions of Pyrazolopyrazine Heterocycles

ul‐Malik

Zaki

El‐Dean

et al. 2018

Journal of Heterocyclic Chem

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“…Thus, the pyrido [2,[3][4][5][6]diazepines (14 and 18) were characterized by an NOE between the substituent R4 and the phenylene protons adjacent to the diazepine ring. 14 In complementary fashion, the observation of NOEs between R4 and the methyl group attached to N-l of the diazepine confirmed the identity of the isomeric pyrido[3,2-6]diazepines 16 and 20. Another feature of interest in the proton NMR spectra of the pyridodiazepinone isomers was that compounds 13, 17, and 21 existed entirely as the imine tautomer in deuteriochloroform, whereas the regio-isomers 15,19, and 23 existed as approximately 1:1 mixtures of enamine and imine tautomers.…”

Section: Chemistrymentioning

confidence: 77%

“…Considering the first four pyrido-fused derivatives 13-16, the regioisomers 13 and 15 were not particularly potent. However, N-methylation caused a significant increase in potency for one regioisomer (14) but not for the other (16). The discovery of potent in vivo activity in 14 prompted us to examine other substituted pyridine derivatives.…”

Section: Resultsmentioning

confidence: 99%

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Novel Antagonists of Platelet-Activating Factor. 2. Synthesis and Structure-Activity Relationships of Potent and Long-Acting Heterofused [1,5]Benzodiazepine and [1,4]Diazepine Derivatives of 1-Phenyl-2-methylimidazo[4,5-c]pyridine

Mj¹,

Dj²,

Cooper³

et al. 1995

J. Med. Chem.

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The optimization of in vitro activity and oral potency and duration of action in vivo is described for three novel structural types of platelet-activating factor (PAF) antagonist: [1,5]benzodiazepines 5-12 onto which a variety of other heterocyclic rings were fused, pyrido[2,3-b][1,4]-diazepinones 13-26, and pyrazolo[3,4-b][1,4]diazepinones 27-46. Compounds 5-12 were prepared by elaboration of the [1,5]benzodiazepine-2-thiones 47 and 48, and 13-46 were prepared by cyclocondensation reactions of a variety of 2,3-diaminopyridine and 4,5-diaminopyrazole derivatives with ethyl 4'-(2-methylimidazo[4,5-c] pyrid-1-yl)benzoylacetate (53). The presence of imine-enamine tautomerism was observed in certain diazepine derivatives and is discussed. Structure-activity relationships were evaluated where PAF antagonist activity was measured in vitro by determining the concentration of compound (IC50) required to inhibit PAF-induced aggregation of rabbit washed platelets and in vivo by determining the oral dose (ED50) which protected mice from a lethal injection of PAF. In addition, the duration of action in conscious dogs as measured by determining the oral dose of selected compounds required to inhibit completely PAF-induced whole blood aggregation ex vivo. The most potent compound was 1,6,7,8-tetrahydro-1,8-dimethyl-5-[4-(2-methylimidazo [4,5-c]pyrid-1-yl)phenyl]-7-oxo-3-(3-pyridyl) pyrazolo[3,4-b][1,4]diazepine (43, UK-91,473) (IC50 = 2.4 nM, ED50 = 0.01 mg/kg po), which was found to be significantly more potent in vivo (murine lethality) than the dihydropyridine PAF antagonist 4-(2-chlorophenyl)-1,4-dihydro-3-(ethoxycarbonyl)-6-methyl- 4-[(2-methylimidazo[4,5-c]pyrid-1-yl)phenyl]-5- [N-(2-pyridyl)carbamoyl]pyridine (4, UK-74,505) (ED50 = 0.26 mg/kg po). Compound 43 also possessed a longer duration of action than compound 4 in the conscious dog at one-fourth of the dose. The crystal structure of compound 43, established by X-ray diffraction, is reported.

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“…Extensive structural modifications of this prototype compound resulted in numerous clinically effective and potent CNS depressants displaying superior pharmacological properties, for example, diazepam (2) [2]. Later, some interesting developments [3][4][5][6][7] in the area of benzodiazepines took place like, an additional heterocyclic ring fused to the different faces of the benzodiazepine ring nucleus as in alprazolam (3), oxazolazepam (4) and the replacement of the benzene ring by naphthalene [8] and different heterocycles (5) like thiophene [9][10][11], pyrrole [12][13], furan [14], imidazole [15], pyrazole [16][17][18][19], thiazole [20], furazan [21], pyridine [22][23][24][25], pyrimidine [26][27], pyrazine [28], indane [29], indole [30][31] and flavone [32]. In 1969 Hofmann and Safir had the interest to study the CNS depressant properties of monocyclic 1,3-dihydro-2H-1,4-diazepin-2-ones (6,7) which are closely related to the benzodiazepines [33].…”

Section: Introductionmentioning

confidence: 99%