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Aims: The current study aimed to synthesize novel pyrazolo[1,5-a]pyrimidines based on 5- aminopyrazoles 3, evaluate their antimicrobial activity, and study the minimum inhibitory concentration (MIC) for the most active compounds. In addition, molecular docking studies and RNA polymerase inhibitory activity were determined. Background: Starting with our previously reported 5-aminopyrazoles 3, a number of novel pyrazolo[1,5- a]pyrimidines were synthesized. Due to the similarity of pyrazolopyrimidine derivatives with the purine systems, pyrazolopyrimidines are important in many different biological applications, most notably as anti-tumor, antibacterial, and hepatitis C virus inhibitors. The pharmaceutical applications of the pyrazolopyrimidine derivatives were explained in several approved drugs like Indiplon, Zaloplan, and Ocinaplon. Objective: To prepare a novel antimicrobial agent, namely pyrazolo[1,5-a]pyrimidine, reveal their structures using different spectral data, the minimum inhibitory concentration (MIC) for the most active compounds was evaluated, and both the molecular docking and the RNA polymerase inhibitory activity were determined. Methods: A number of different pyrazolopyrimidines namely 2-(phenylamino)-6,11-dihydrobenzo[g]pyrazolo [1,5-a]quinazoline-3-carboxamides (5a-c), (E)-5,7-dimethyl-2-(phenylamino)-6-(phenyldiazenyl)pyrazolo-[1,5- a]pyrimidine-3-carboxamides (7a-c), 7-amino-2-(phenylamino) pyrazolo[1,5-a]pyrimidine-3-carboxamides (11af), 7-amino-2-(phenylamino)-5-(2-thienyl)pyrazolo[1,5-a]pyrimidine-3-carboxamides (14-f) and ethyl 7-amino-3- carbamoyl-2-(phenylamino)-5-(4-pyridyl)pyrazolo[1,5-a]pyrimidine-6-carboxylate derivatives (14g-i) were synthesized through the reaction of 5-aminopyrazoles 3 with a variety of chemical reagents. On the other hand, the evaluation of the antimicrobial activity for all the prepared compounds was screened through different strains as Gram-positive bacteria, such as staphylococcus aureus and Streptococcus mutans, and Gram-negative bacteria, such as Escherichia coli, Pseudomonas aeruginosa, and klebsiella. The antifungal activity was determined by Candids Albicans fungal strain, and the MIC of the most active compounds was measured. The molecular docking was recorded, and the RNA polymerase inhibitory activity was estimated for the high docking score compounds. Results: Compounds 5a, 5b, 5c, 7a, 7b, 7c, 11d, 14b, and 14h were the most active compounds against some of the bacterial and fungal tested strains. MIC was determined for the most active tested compounds. As an antimicrobial agent, compound 7b was the most potent, with a high docking score and RNA polymerase inhibitory activity (IC50= 0.213 μg/ml) compared to Rifampicin (IC50= 0.244 μg/ml). The reactivity of the latter compound was attributed to the presence of 4-Br-C6H4 moiety. The results demonstrated that docking studies on the most active compounds in the RNA polymerase active site were consistent with in vitro assays. Conclusion: The resultant novel bioactive pyrazolo[1,5-a]pyrimidine derivatives were synthesized based on 5- aminopyrazole derivatives 3. The current study evaluated the antimicrobial activity for all the prepared compounds, followed by the determination of the MIC for the most potent active compounds. The molecular docking study was performed, and it was appropriate with the in vitro activity. The RNA polymerase inhibitory activity was assessed for the most active antimicrobial compounds with a high docking score (7b, 7c, 14a, 14b, 14e, 14i). Compound 7b was the most potent compound inhibiting RNA polymerase enzyme compared to the reference drug Rifampicin. Other: The novel prepared heterocyclic systems are extremely important in a variety of domains, especially biological and pharmacological ones.

Background: Due to their biological applications, many tetrahydrobenzo[d]thiazole derivatives were considered the most important class of heterocyclic compounds. There are many drugs known in the market containing the thiazole moiety responsible for the high drug activity. Objective: This work aimed to produce novel heterocyclic compounds such as pyrazole, isoxazole, thiophene, chromeno[7,8-d]thiazole, and thiazolo[4,5-h]quinoline derivatives. The newly synthesized heterocyclic compounds were evaluated against anticancer cell lines followed by c-Met enzymatic activity and tyrosine kinases inhibition for the most active compounds. Methods: In this work, the 3-phenyl-2-thioxo-2,3,5,6-tetrahydrobenzo[d]thiazol-7(4H)-one (3) was synthesized through the reaction of cyclohexane-1,3-dione with phenyl isothiocyanate and elemental sulfur. Compound 3 showed interesting activity toward some chemical reagents producing new heterocyclic compounds that can not be obtained another way. The newly synthesized compounds were evaluated towards the six cancer cell lines. The most active compounds were selected and tested toward the c-Met enzyme by taking foretinib as the positive control. Also, the inhibitions toward the PC-3 cell line using the reference SGI-1776 were measured. Finally, the inhibitions towards the five tyrosine kinases were also tested. Results: The synthesized quinoline and chromene derivatives were evaluated toward the c-Met enzyme using foretinib as the positive control. The obtained results showed that twelve compounds exhibited IC50 values less than 1.30 nM. On the other hand, sixteen compounds showed higher inhibitions than the reference SGI-1776 (IC50 4.86 nM) toward the PC-3 cell line. Conclusion: Novel, heterocyclic compounds were synthesized with a high impact on biological activities. All synthesized compounds were screened for their anti-proliferative effect, and most of them revealed high potent effects. In addition, the c-Met and prostate cancer cell line PC-3 inhibitions for the most active compounds showed that these compounds exhibited high inhibitions. Anti-proliferative activity of selected compounds toward cancer cell lines classified according to the disease showed that most compounds exhibited high inhibitions.

The title compound, C23H15BrN2OS, was the unexpected product in an attempted synthesis of the isomeric 3-(benzo[d]thiazol-2-yl)-6-bromo-1-p-tolylquinolin-2(1H)-one. The Cchromene=N—C angle is wide [125.28 (8)°]. The benzothiazole and chromene ring systems are almost coplanar, with their planes parallel to (1\overline{1}0); the toluene ring system is rotated by ca 40° out of the chromene plane. The molecular packing involves layers with π-stacking, borderline `weak' hydrogen bonds and possible C—H...π contacts.

In the title compound, C16H9NO2S, the interplanar angle is 6.47 (6)°. An intramolecular S...O=C contact of 2.727 (2) Å is observed. The packing is determined by several types of weak interaction (`weak' hydrogen bonds, S...S contacts and π–π stacking).

In the title compound, C

Many novel thiazole derivatives were designed and synthesized using 4-phenylthiazol-2-amine. The reactivity of the latter compound toward different chemical reagents was studied. The structure of the newly synthesized compounds was established based on elemental analysis and spectral data. Furthermore, twenty compounds of the synthesized systems were selected and evaluated in (µM) as significant anticancer agents towards three human cancer cell lines [MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and SF-268 (CNS cancer)] and normal fibroblasts human cell line (WI-38). The results showed that compounds 9 and 14a displayed higher effeciency than the reference doxorubicin.