New Series of Antiprion Compounds:  Pyrazolone Derivatives Have the Potent Activity of Inhibiting Protease-Resistant Prion Protein Accumulation

Kimata, Ayako; Nakagawa, Hidehiko; Ohyama, Ryo; Fukuuchi, Tomoko; Ohta, Shigeru; Doh‐ura, Katsumi; Suzuki, Takayoshi; Miyata, Naoki

doi:10.1021/jm070688r

Cited by 190 publications

(72 citation statements)

References 27 publications

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“…The starting intermediates 1-(4-substitutedphenyl)-3-methyl-1H-pyrazol-5(4H)-ones 2a and 2c were synthesized by reacting the commercially available 4-chlorophenylhydrazine hydrochloride 1a or the synthesized 4-hydrazinylbenzenesulfonamide hydrochloride 1b 25) with ethyl acetoacetate in acetic acid in the presence of sodium acetate to obtain 2a [26][27][28] or in refluxing methanol to obtain 2c. 29,30) Methylation of 2a and 2c with dimethylsulfate (DMS) in alkaline medium afforded the N-methyl derivatives 3a 31) and 3d.…”

Section: Resultsmentioning

confidence: 99%

“…All the reactions were followed by TLC using silica gel F254 plates (Merck), using chloroform: methanol 9 : 1 or chloroform as eluting system and were visualized by UV-lamp. Compounds 1b, 25) and 3a 31) were prepared according to reported methods, while compounds 8a, 36) 8b, 46) 2a, [26][27][28] 2c, 29,30) 2b, [33][34][35] and 3d 32) were prepared according to modified procedures from the reported methods.…”

Section: Methodsmentioning

confidence: 99%

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Pyrazolone Derivatives: Synthesis, Anti-inflammatory, Analgesic, Quantitative Structure–Activity Relationship and <i>in Vitro</i> Studies

et al. 2013

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Some 1-(4-chlorophenyl or benzenesulfonamide)-2,3-and/or 4-substituted-1H-pyrazol-5(4H)-one derivatives were synthesized and screened for their anti-inflammatory and analgesic activities, in addition to their ulcerogenic liability. They were found to be active as anti-inflammatory and analgesic agents. Compound 6b was found to be the most active as anti-inflammatory agent and compound 9b was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, cyclooxygenase-1/-2 (COX-1)/COX-2 isozyme selectivity was also done and the tested compounds showed equal inhibition to both isoforms. Moreover, 2D-quantitative structure-activity relationship (QSAR) studies revealed well predictive and statistically significant and cross validated QSAR model that helps to explore some expectedly potent compounds.Key words pyrazolone; acetic acid; quantitative structure-activity relationship; cyclooxygenase inhibition; anti-inflammatory Non steroidal anti-inflammatory drugs (NSAIDs) were known as important class of therapeutic agents for the alleviation of pain and inflammation. The pharmacological activity of NSAIDs is due to the inhibition of prostaglandins biosynthesis from arachidonic acid through inhibiting cyclooxygenases (COXs).1,2) However, long term use of NSAIDs was associated with several side effects such as gastrointestinal mucosal damage, bleeding, intolerance, and renal toxicity. 3-6)The gastrointestinal (GI) damage from NSAIDs generally attributes to two factors, i.e., local irritation by the carboxylic acid moiety, common to most NSAIDs (topical effect) and decreased tissue prostaglandins production which maintains GI health and homeostasis. Therefore, synthetic approaches based upon chemical modification of NSAIDs were taken with the aim of improving NSAID safety profile. 7-10)The core pyrazolone structure generally attracted widespread attention because of the diversity of biological activity as they showed anti-inflammatory [11][12][13] analgesic, 14,15) antitumor, 16) antimicrobial, 17,18) hypoglycemic, 19) and antitubercular 20) activities. One of the first synthetic organic compounds that used as an important drug and having a pyrazolone nucleus was antipyrine I. 21) In addition, many pyrazolones like aminophenazone II, propyphenazone III, and famorofazone IV (Fig. 1) are widely used as anti-inflammatory, analgesic, and antipyretic drugs. 7,22,23) Besides, different pyrazolones found to possess significant anti-inflammatory activity as compounds V, 24) VI, 11) VII, 11) and VIII 13) (Fig. 2). Thus, our main objective is to design novel pyrazolone derivatives to be further explored as powerful and novel nonulcerogenic anti-inflammatory lead candidates. Some of these derivatives contain acidic centers with further esterification aiming to decrease the local side effects that might be attained by its acidic moieties.The synthesized compounds were evaluated for their antiinflammatory and analgesic activities. Ulcerogenic liability was also performed; in addition, evaluation for the...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Pyrazolone Derivatives: Synthesis, Anti-inflammatory, Analgesic, Quantitative Structure–Activity Relationship and <i>in Vitro</i> Studies

et al. 2013

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“…Several pyrazoline derivatives found to possess antimicrobial 33 and anti-HIV 34 activities. Some of the pyrazolines were effective in inhibiting the accumulation of prion protein 35 , the abnormal protease-resistant form.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Some Fluorinated 1, 5 - Benzothiazepines and Pyrazolines

Jagadhani¹,

Kundlikar²,

Karale³

2015

Orient. J. Chem

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ABSTRACT4-Bromo-2-fluorobenzaldehyde 1 when treated with substituted hydroxy acetophenones 2 yields chalcones 3. These chalcones were refluxed with 2-aminothiophenol gave "2-[2-(4-bromo-2-fluorophenyl)-2,3-dihydro-1,5-benzothiazepin-4-yl]phenol" 4 and when treated with hydrazine hydrate gave the compound "2- [5-(4-bromo-2-fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]phenol" 5. The structures of compounds have been established on the basis of spectral data.

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“…Pyrano [2,3-c]pyrazole derivatives show many bioactivities such as antimicrobial [32], insecticidal [33], anti-inflammatory activities [34] and molluscicidal activity [35,36]. Pyrano [2,3-c]pyrazoles are known have application in screening kit for Chk1 kinase inhibitor [37,38] and also used as photoactive material [39].…”

Section: Introductionmentioning

confidence: 99%

Glycerol mediated, one pot, multicomponent synthesis of dihydropyrano[2,3-c]pyrazoles

Sohal¹,

Goyal²,

Sharma³

et al. 2013

Eur. J. Chem.

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New Series of Antiprion Compounds: Pyrazolone Derivatives Have the Potent Activity of Inhibiting Protease-Resistant Prion Protein Accumulation

Cited by 190 publications

References 27 publications

Pyrazolone Derivatives: Synthesis, Anti-inflammatory, Analgesic, Quantitative Structure–Activity Relationship and <i>in Vitro</i> Studies

Pyrazolone Derivatives: Synthesis, Anti-inflammatory, Analgesic, Quantitative Structure–Activity Relationship and <i>in Vitro</i> Studies

Synthesis and Characterization of Some Fluorinated 1, 5 - Benzothiazepines and Pyrazolines

Glycerol mediated, one pot, multicomponent synthesis of dihydropyrano[2,3-c]pyrazoles

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