• Archives of Pharmacal Research
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• 제10권3호
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• pp.173-178
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• 1987

Several new pyrazolo [1, 5-a]-S-triazine, pyrazolo [4, 5, -elpyrimidine, pyrazolo [1, 5-a] pyrimidine derivatives were synthesized via condensation of 3-antipyrinyl-5-amino-pyrazole (2) with $\beta$$-bifunctional reagents. The azo analogues of pyrazolo [1, 5-a] pyrimidines ; i. e. pyrazolo [5, 1, c]-as-triazine and pyrazolo[5, 1, -c]-as-benzotriazine were synthesized by coupling of diazotized 2-with agents containing active hydrogen.

• 대한화학회지
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• 제55권5호
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• pp.781-786
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• 2011

An easy and efficient route for the synthesis of some imidazo[1,2-c]pyrazolo[4,3-e]pyrimidines 3-6, imidazo[1,2-c]pyrazolo[4,3-e]triazine 8, pyrazolo[4,3-e]triazolo[1,5-c]pyrimidines 12-15 and pyrazolo-[3',4':4,5]pyrimido[1,6-b]triazines 16, 17 was described through the reaction of readily available 5-aminopyrazole-4-carbonitrile 1 with different reagents. The in vitro antimicrobial activity of some synthesized compounds was examined. Most of the tested compounds proved to be active as antibacterial and antifungal agents.

• 대한방사성의약품학회지
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• 제8권1호
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• pp.33-37
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• 2022

Translocator protein (TSPO) is associated with neurodegeneration diseases, and the development of potent ligands with high affinity to TSPO was valuable study for many scientists. Specially, pyrazolo[1,5-a]pyrimidine moiety has been employed for development of new TSPO ligands with good properties. In this highlight review, the development of [¹⁸F]F-DPA as a promising TSPO ligand as PET tracer is described.

• 대한방사성의약품학회지
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• 제2권2호
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• pp.69-72
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• 2016

Since the translocator protein (TSPO) is involved in neurodegeneration diseases, many scientists' interest has been focused on the development of a ligand targeting TSPO. A novel compound based on pyrazolo[1,5 -a] pyrimidine structure, DPA-714, has been studied and considered as a TSPO ligand with high affinity. In this highlight review, several researches for the novel radioligand for the translocator protein are illustrated.

• 대한화학회지
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• 제55권4호
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• pp.719-722
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• 2011

• Archives of Pharmacal Research
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• 제20권6호
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• pp.620-628
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• 1997

6-Aryl-5-cyano-4-pyrimidinon-2-thione derivatives 1a-c reacted with ethyl iodide to give the corresponded 2-S-ethylpyrimidin-4-one-derivatives 2a-c. Compounds 2a-c was, in turn, reacted with hydrazine hydrate to give the sulfur free reaction products, 3a-c. These reaction products were taken as the starting materials for the synthesis of several newly synthesized heterocyclic derivatives. Reactions with several halogenated ketones, esters, chloroacetic acid and chloroacetamide give pyrimidotriazines 8,12 and 15 while their reactions with formic acid, acetic acid and carbon disulfide gave the corresponded triazolopyrimidines 17 and 21. The reaction with both acetyl acetone and ethylacetoacetate gave the corresponded 2-$(3^{I},5^{I}-dimethyl-1^{I}-pyrazoly$pyrimidine derivatives 20a-c and 24a-c respectively while the reaction with cinnamonitriles 25a-h afforded the corresponded aryl hydrazopyrimidines 27a-f. The structure of these reaction products were eatablished based on both elemental anlayses and spectral data studies.

• Bulletin of the Korean Chemical Society
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• 제24권10호
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• pp.1429-1432
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• 2003

A novel fused thiouracil containing a heterocyclic ring system, dipyrimidinopyridine (3), has been prepared through the cyclization of compound 2. Compound 2 was formed by the formylation of 6-amino-2-thiouracil 1, pyrazolopyrimidines 8-10 via the heating of 6-arylhydrazono-2-thiouracils 5-7, compound 11, using Vilsmeier reagent with compound 4, pyrazolylpyrimidine 12, indolodiazinopyrimidine 14 and pyridazinopyrimidine 15. Pyridazino-pyrimidine 15 was formed by the condensation of compound 4 with acetylacetone, isatin and benzyl, respectively.

• 대한화학회지
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• 제45권5호
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• pp.448-453
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• 2001

피라졸로아진은 농업이나 의약품에서 매우 유용한 화합물등이다. 본 논문에서는 몇 가지 새로운 피라졸로아진의 합성을 보고하고자 한다. 표제 화합물인 3-아미노-1H-피라졸-4-카복실산 에틸을 다이아조화한 후 활성화된 메틸렌 화합물들과 반응시키고 고리화하여 피라졸로[5,1-c][1,2,4]트라이아진 유도체들을 합성하였다. 또한 표제 화합물을 $\alpha$-치환된 신남나이트릴과 반응시켜 피라졸로[1,5-a]피리미딘 유도체들을 합성하였다. 새로 합성된 화합물들의 구조는 화학적 방법과 분광학적 방법을 사용하여 확립하였다.

• IMMUNE NETWORK
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• 제6권4호
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• pp.204-210
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• 2006

Background: Nitric oxide (NO) in articular chondrocytes regulates dedifferentiation and inflammatory responses by modulating MAP kinases. In this study, we investigated whether the Src kinase in chondrocytes regulates NO-induced dedifferentiation and cyclooxygenase-2 (COX-2) expression. Methods: Primary chondrocytes were treated with various concentrations of SNP for 24 h. The COX-2 and type II collagen expression levels were determined by immunoblot analysis, and prostaglandin $E_2\;(PGE_2)$ was determined by using a $PGE_2$ assay kit. Expression and distribution of p-Caveolin and COX-2 in rabbit articular chondrocytes and cartilage explants were determined by immunohistochemical staining and immunocytochemical staining, respectively. Results: SNP treatment stimulated Src kinase activation in a dose-dependent manner in articular chondrocytes. The Src kinase inhibitors PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine], a significantly blocked SNP-induced p38 kinase and caveolin-1 activation in a dose-dependent manner. Therefore, to determine whether Src kinase activation is associated with dedifferentiation and/or COX-2 expression and $PGE_2$ production. As expected, PP2 potentiated SNP-stimulated dedifferentiation, but completely blocked both COX-2 expression and $PGE_2$ production. And also, levels of p-Caveolin and COX-2 protein expression were increased in SNP-treated primary chondrocytes and osteoarthritic and rheumatoid arthritic cartilage, suggesting that p-Caveolin may playa role in the inflammatory responses of arthritic cartilage. Conclusion: Our previously studies indicated that NO caused dedifferentiation and COX-2 expression is regulated by p38 kinase through caveolin-1 (1). Therefore, our results collectively suggest that Src kinase regulates NO-induced dedifferentiation and COX-2 expression in chondrocytes via p38 kinase in association with caveolin-1.

• Biomolecules & Therapeutics
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• 제20권4호
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• pp.393-398
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• 2012

Recently, we reported that defective autophagy may contribute to the inhibition of the growth in response to PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), a selective SFK inhibitor, in multidrug-resistant v-Ha-ras-transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr). In this study, we demonstrated that PP2 induces LC3 conversion via a mechanism that is uncoupled from autophagy and increases apoptosis in Ras-NIH 3T3/Mdr cells. PP2 preferentially induced autophagy in Ras-NIH 3T3 cells rather than in Ras-NIH 3T3/Mdr cells as determined by LC3-I to LC3-II conversion and GFP-LC3 fluorescence microscopy. Beclin 1 knockdown experiments showed that, regardless of drug resistance, PP2 induces autophagy via a Beclin 1-dependent mechanism. PP2 induced a conformational change in Beclin 1, resulting in the enhancement of the pro-autophagic activity of Beclin 1, in Ras-NIH 3T3 cells. Further, PI3K inhibition induced by wortmannin caused a significant increase in apoptosis in Ras-NIH 3T3 cells, as demonstrated by flow cytometric analysis of Annexin V staining, implying that autophagy inhibition through PI3K increases apoptosis in response to PP2 in Ras-NIH 3T3 cells. However, despite the fact that wortmannin abrogates PP2-induced GFP-LC3 punctae formation, some LC3 conversion remains in Ras-NIH 3T3/Mdr cells, suggesting that LC3 conversion may occur in an autophagy-independent manner. Taken together, these results suggest that PP2 induces LC3 conversion independent of PI3K, concomitant with the uncoupling of LC3 conversion from autophagy, in multidrug-resistant cells.