Synthesis and Neurotropic Activity of Novel Condensed Cyclopentanopyrido[3',2':4,5]-Thieno[3,2-D]Pyrimidine Derivatives

Thiazolopyrimidine 2 was obtained from the reaction of dihydropyrimidinone with chloroacetic acid and benzaldehyde. Thiazolopyrimidine 2 containing an α,β-unsaturated ketonic function [-CH=CH-CO-] has been used as a component of Michael addition with an equimolar amount of dinucleophiles to give a series of novel tetracyclic pyrimidine derivatives. Treatment of thiazolopyrimidine 2 with uracil, aminotriazole, cyanoacetic acid hydrazide, o-phenylenediamine or diaminopyridine afforded the corresponding pyridopyrimidine, triazolopyrimidine, pyrazolone, benzodiazepine and triazepine derivative, respectively. The detailed synthesis, spectroscopic data, and antitumor activity for synthesized compounds were reported.

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Comparative Study of the Biologically Active Substances Composition and Content in Meadowsweet (Filipendula ulmaria (L.) Maxim) Crude Herbal Drugs (Herb, Leafs, Flowers) of Russian Origin

International Journal of Pharmaceutical Quality Assurance ◽

10.25258/ijpqa.v9i3.13660 ◽

2018 ◽

Vol 9 (3) ◽

Author(s):

Dmitry Olegovich Bokov ◽

Tatyana Yuryevna Kovaleva ◽

Valentina Alekseevna Ermakova ◽

Daria Aleksandrovna Trashchenkova ◽

Ekaterina Anatolievna Dorovskih ◽

...

Keyword(s):

Traditional Medicine ◽

Neurotropic Activity ◽

Comparative Investigation ◽

Biologically Active ◽

Total Flavonoids ◽

Herbal Drugs ◽

Filipendula Ulmaria ◽

Pharmacopoeial Monograph ◽

Total Extractives ◽

Layer Chromatography

Filipendula ulmaria (L.) Maxim. (Meadowsweet) is known in traditional medicine as anti-inflammatory, wound-healing,astringent and antibacterial remedy. However recent studies show that it also has neurotropic activity. In Russia meadowsweet flowers are used as crude herbal drugs (temporary pharmacopoeial monograph 42-1777-87), also leafs and herb are used in the traditional medicine. Objective of the study was to carry out comparative investigation of composition and content of major biologically active compounds (BAC) in Filipendula ulmaria herb, flowers and leafs by thin-layer chromatography, differential spectrophotometry with aluminum chloride reagent (total flavonoids in terms of rutoside), gravimetry (total extractives, extracted by water), permanganatometric titration (total tannins in terms of tannin). Rutoside, tannin, gallic acid and salicylic acid were identified in Filipendula ulmaria herb, flowers and leafs by TLC. Also we analyzed content of substances extracted by water, flavonoids and tannins. Total extractives, extracted by water in F. ulmaria herb is 13.12±0.10%, in leafs – 13.98±0.37%, in flowers – 18.09±0.17%. Total tannins in F. ulmaria herb is 11.87±0.47%, in leafs – 12.06±0.18%, in flowers – 12.26±0.29%. Total flavonoids in F. ulmaria herb 4.34±0.17%, in leafs – 6.98±0.23%, in flowers – 11.75±0.57%. The obtained data will be used for development of a pharmacopoeial monograph project "Filipendula ulmaria (L.) Maxim., herba" for inclusion in the State Pharmacopoeia of the Russian Federation.

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Facile construction of novel fused chromeno[2,3-d]thiazolo[3,2-a]pyrimidine derivatives in biocompatible ionic liquid under solvent-free conditions_ESI

Journal of Chemical Research ◽

10.3184/174751918x15433174237340 ◽

2018 ◽

Keyword(s):

Ionic Liquid ◽

Solvent Free ◽

Pyrimidine Derivatives

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Synthesis of New Bithiophene and Thieno [2,3-d] Pyrimidine Derivatives with Potent Antimicrobial Activity

Egyptian Journal of Chemistry ◽

10.21608/ejchem.2010.1229 ◽

2010 ◽

Vol 53 (3) ◽

pp. 385-401

Keyword(s):

Antimicrobial Activity ◽

Pyrimidine Derivatives

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An Update on JAK Inhibitors

Current Medicinal Chemistry ◽

10.2174/0929867325666180327093502 ◽

2019 ◽

Vol 26 (10) ◽

pp. 1806-1832 ◽

Cited By ~ 10

Author(s):

Francesca Musumeci ◽

Chiara Greco ◽

Ilaria Giacchello ◽

Anna Lucia Fallacara ◽

Munjed M. Ibrahim ◽

...

Keyword(s):

Clinical Trials ◽

Tyrosine Kinases ◽

Chemical Structure ◽

Receptor Tyrosine Kinases ◽

Myeloproliferative Neoplasms ◽

Pharmaceutical Companies ◽

Jak Inhibitors ◽

Pyrimidine Derivatives ◽

Janus Kinases ◽

Structure Activity

Janus kinases (JAKs) are a family of non-receptor tyrosine kinases, composed by four members, JAK1, JAK2, JAK3 and TYK2. JAKs are involved in different inflammatory and autoimmune diseases, as well as in malignancies, through the activation of the JAK/STAT signalling pathway. Furthermore, the V617F mutation in JAK2 was identified in patients affected by myeloproliferative neoplasms. This knowledge prompted researchers from academia and pharmaceutical companies to investigate this field in order to discover small molecule JAK inhibitors. These efforts recently afforded to the market approval of four JAK inhibitors. Despite the fact that all these drugs are pyrrolo[2,3-d]pyrimidine derivatives, many compounds endowed with different heterocyclic scaffolds have been reported in the literature as selective or multi-JAK inhibitors, and a number of them is currently being evaluated in clinical trials. In this review we will report many representative compounds that have been published in articles or patents in the last five years (period 2013-2017). The inhibitors will be classified on the basis of their chemical structure, focusing, when possible, on their structure activity relationships, selectivity and biological activity. For every class of derivatives, compounds disclosed before 2013 that have entered clinical trials will also be briefly reported, to underline the importance of a particular chemical scaffold in the search for new inhibitors.

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QSAR Studies of Halogenated Pyrimidine Derivatives as Inhibitors of Human Dihydroorotate Dehydrogenase Using Modified Bee Algorithm

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666180611092540 ◽

2018 ◽

Vol 21 (5) ◽

pp. 381-387 ◽

Cited By ~ 1

Author(s):

Hossein Atabati ◽

Kobra Zarei ◽

Hamid Reza Zare-Mehrjardi

Keyword(s):

External Validation ◽

Correlation Coefficients ◽

Quantitative Structure Activity Relationship ◽

Molecular Structures ◽

Dihydroorotate Dehydrogenase ◽

Pyrimidine Derivatives ◽

Qsar Studies ◽

Bee Algorithm ◽

Test Sets ◽

Leave One Out

Aim and Objective: Human dihydroorotate dehydrogenase (DHODH) catalyzes the fourth stage of the biosynthesis of pyrimidines in cells. Hence it is important to identify suitable inhibitors of DHODH to prevent virus replication. In this study, a quantitative structure-activity relationship was performed to predict the activity of one group of newly synthesized halogenated pyrimidine derivatives as inhibitors of DHODH. Materials and Methods: Molecular structures of halogenated pyrimidine derivatives were drawn in the HyperChem and then molecular descriptors were calculated by DRAGON software. Finally, the most effective descriptors for 32 halogenated pyrimidine derivatives were selected using bee algorithm. Results: The selected descriptors using bee algorithm were applied for modeling. The mean relative error and correlation coefficient were obtained as 2.86% and 0.9627, respectively, while these amounts for the leave one out−cross validation method were calculated as 4.18% and 0.9297, respectively. The external validation was also conducted using two training and test sets. The correlation coefficients for the training and test sets were obtained as 0.9596 and 0.9185, respectively. Conclusion: The results of modeling of present work showed that bee algorithm has good performance for variable selection in QSAR studies and its results were better than the constructed model with the selected descriptors using the genetic algorithm method.

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