Automated parallel synthesis of chalcone-based screening libraries

Powers, David G.; Casebier, David S.; Fokas, Demosthenes; Ryan, William J.; Troth, J. R.; Coffen, David L.

doi:10.1016/s0040-4020(98)00137-9

Cited by 170 publications

(78 citation statements)

References 4 publications

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“…The mass spectrum of the same compound showed two isotopic molecular ion peaks at m/z 297 and 299 which is in agreement with its molecular formula. In addition, the mass spectra of the chalcone derivatives IIb-f exhibited the molecular ion peaks of the compounds confirming their structural formulae These chalcones are considered to be useful intermediates in several cyclization reactions to produce different types of heterocyclic compounds according to the used reactants and the reaction's conditions 40,41 . Thus, in the present investigation, the target quinazolines IIIa,b, VIa,b and Va,b were obtained by condensation of the prepared chalcones IIa,b with urea , thiourea and guanidine salt respectively in refluxing ethanol under alkaline medium conditions.…”

Section: Chemistrymentioning

confidence: 74%

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Synthesis and Antimicrobial Evaluation of Some Tricyclic Substituted benzo[h]quinazolines, benzo[h]quinolines and naphthaleno[d]thiazoles

Ebied

Zaghary

Amin

et al. 2017

Journal of Advanced Pharmacy Research

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Objectives: The notable advancing in the medicinal chemistry arena against infectious diseases has resulted in the discovery of numerous valuable antimicrobial drugs that saved millions of lives throughout the last few decades. Nevertheless, the continuous reporting of multi-drug resistant strains of a number of diverse germs makes the need for novel broad-spectrum anti-infective agents still exists. Methods: Three series of ring-equivalent tricyclic benzo The antimicrobial activity of some of the synthesized compounds was screened and only 2-bromo derivative IX and aminothiazole compound X exhibited broad antimicrobial effectiveness. The antifungal MIC value of X was1.85 mg/mL. Conclusion:The new synthesized compounds, designed as bioisosteres, showed excellent potency against the tested gram (+) bacterial and fungal strains compared to reference drugs.

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Section: Chemistrymentioning

confidence: 74%

“…These chalcones were synthesized via Claisen-Schemidt condensation, a type of aldol condensation of aromatic aldehydes with the corresponding substituted acetophenone in the presence of sodium, potassium or barium hydroxide [39,40] as illustrated in Scheme 1.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Antimicrobial Evaluation of Some Tricyclic Substituted benzo[h]quinazolines, benzo[h]quinolines and naphthaleno[d]thiazoles

Ebied

Zaghary

Amin

et al. 2017

Journal of Advanced Pharmacy Research

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“…1) Pyrimidine derivatives have been the subject of substantial attention by synthetic and medicinal chemists because of the role of this heteroaromatic ring in many biological activities such as anticancer, 2) antiviral, 3) antitumor, 4) anti-inflammatory, 5) antimicrobial, 6) antifungal, 7) antihistaminic, 8) and analgesic activities. 9) Novel immunosuppressive agents like 2-aminoquinazolines 10) and aminopyrimidine amides 11) were target components of signal transduction pathways mediated by the T cell receptor (TCR) may be useful as therapies for T-cell-mediated inflammatory or autoimmune diseases such as rheumatoid arthritis, polyarthritis scleroderma, inflammatory bowel disease, type 1 diabetes, myasthenia gravis and lupus.…”

Section: Regular Articlementioning

confidence: 99%

A Study of Anti-inflammatory and Analgesic Activity of New 2,4,6-Trisubstituted Pyrimidines

Yejella

Atla

2011

CHEMICAL & PHARMACEUTICAL BULLETIN

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Chalcone derivatives (3a-m) were prepared by condensing 4-aminoacetophenone with various substituted aromatic and hetero aromatic aldehydes according to Claisen-Schmidt condensation. These chalcones, on reaction with guanidine hydrochloride under basic alcoholic conditions gave 2,4,6-trisubstituted pyrimidines (5a-m) in quantitative yields. All the newly synthesized pyrimidines were characterized by means of IR, 1 H-and 13 C-NMR, Electron Ionization (EI)-mass and elemental analyses and screened for anti-inflammatory and analgesic activities by in vivo. 2-Amino-4-(4-aminophenyl)-6-(2,4-dichlorophenyl)pyrimidine (5b) and 2-amino-4-(4-aminophenyl)-6-(3-bromophenyl) pyrimidine (5d) were found to be the most potent anti-inflammatory and analgesic activity compared with ibuprofen, reference standard. And also it was found that compound 5b identified as lead structure among all in both the activities. Pyrimidines which showed good anti-inflammatory activity also displayed better analgesic activity.

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“…Estas coleções de moléculas com estruturas "privilegiadas" são muito encontradas na literatura, sendo que as coleções de benzodiazepinas são um bom exemplo desta estratégia 6 . Embora inicialmente algumas empresas tenham comercializado coleções combinatórias contendo milhares de compostos, planejadas para cobrir ampla faixa de diversidade estrutural e Powers e col. reportaram a preparação de coleções combinatórias derivadas da coleção de 1280 chalconas de estrutura geral 9 previamente preparadas (Esquema 4) 27 . A primeira coleção foi obtida a partir da condensação aldólica de 32 acetofenonas e 40 aldeídos aromáticos, fornecendo as 1280 chalconas 9.…”

Section: Identificação De Um Composto-protótipounclassified

Aplicações da química combinatória no desenvolvimento de fármacos

Dias¹,

Corrêa²

2001

Quím. Nova

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Recebido em 17/2/00; aceito em 28/8/00 APPLICATIONS OF COMBINATORIAL CHEMISTRY TO DRUG DEVELOPMENT. Combinatorial Chemistry has become a very efficient methodology in drug research. Recent progress in combinatorial synthesis performed both in solid and solution phase have led to a change in the paradigm for the identification and optimization of lead compounds. This article gives an overview of the principal characteristics of combinatorial libraries and some examples of the application of this methodology in the identification of test compounds and lead compound optimization, either from synthetic or natural sources.Keywords: combinatorial chemistry; drug development; small molecule libraries. Quim. Nova, Vol. 24, No. 2, 236-242, 2001. Divulgação INTRODUÇÃOO processo de desenvolvimento de fármacos incorporou profundas transformações no decorrer da última década. Com o avanço da Biologia Molecular inúmeros processos biológicos foram identificados, fornecendo assim diversos novos alvos macromoleculares passíveis de intervenção terapêutica. Paralelamente, a miniaturização e o desenvolvimento de dispositivos automatizados para a realização de ensaios biológicos automatizados (do inglês, High Throughput Screening, HTS) possibilitaram a avaliação de uma grande quantidade de substâncias frente a estes novos alvos. A resposta a esta demanda crescente por substâncias estruturalmente inovadoras para avaliação farmacológica estabeleceu um novo paradigma na busca por compostos-protótipo e na otimização/desenvolvimento dos já existentes. A preparação conjunta -na forma de misturas -ou paralela -na forma de substân-cias puras -de coleções com grande número de compostos estruturalmente relacionados, com sequências de reação semelhantes e com diversidade estrutural gerada pela introdução de blocos de construção com diferentes grupos substituintes promoveu uma grande transformação em relação aos métodos até então utilizados no planejamento de fármacos [1][2][3][4][5] . Ainda incipiente e restrita à preparação de coleções de peptídeos e nucleotídeos, a Química Combinatória apresentou um crescimento vertiginoso desde a preparação de uma coleção combinatória de benzodiazepinas em 1992, trabalho pioneiro realizado por Ellmann e col., que consistiu na primeira coleção combinatória de moléculas orgânicas pequenas 6 . A Química Combinatória extrapolou a esfera da Química Medicinal e vem sendo crescentemente utilizada nas áreas de agroquímicos, catálise homogênea e heterogênea, biocatálise, novos materiais, entre outros 1-4 . A Figura 1 apresenta a evolução do número de publicações científicas na área de Química Combinatória ao longo dos últimos anos 7 . As coleções combinatórias podem ser divididas entre as preparadas por síntese paralela, onde as etapas sintéticas são realizadas simultaneamente, mas cada composto é preparado em um compartimento de reação separadamente, e as preparadas na forma de mistura, ou seja, a um substrato é adicionado uma mistura de reagentes (building blocks), fornecendo então uma mistura de produtos. Por dem...

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Automated parallel synthesis of chalcone-based screening libraries

Cited by 170 publications

References 4 publications

Synthesis and Antimicrobial Evaluation of Some Tricyclic Substituted benzo[h]quinazolines, benzo[h]quinolines and naphthaleno[d]thiazoles

Synthesis and Antimicrobial Evaluation of Some Tricyclic Substituted benzo[h]quinazolines, benzo[h]quinolines and naphthaleno[d]thiazoles

A Study of Anti-inflammatory and Analgesic Activity of New 2,4,6-Trisubstituted Pyrimidines

Aplicações da química combinatória no desenvolvimento de fármacos

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