Day: December 6, 2022

Pismataro, Maria Chiara published the artcile1,2,4-Triazolo[1,5-a]pyrimidines: Efficient one-step synthesis and functionalization as influenza polymerase PA-PB1 interaction disruptors, HPLC of Formula: 1455-77-2, the main research area is triazolopyrimidine preparation antiviral influenza polymerase PA PB1 interaction disruptor; 1,2,4-triazolo[1,5-a]pyrimidines; Antiviral agents; Influenza polymerase; Influenza virus; PA-PB1 interaction; Protein-protein interaction; SARS-CoV-2.

In the search for new anti-influenza virus (IV) compounds, the 1,2,4-triazolo[1,5-a]pyrimidine (TZP) was identified as a very suitable scaffold to obtain compounds able to disrupt IV RNA-dependent RNA polymerase (RdRP) PA-PB1 subunits heterodimerization. To this aim, four facile and efficient one-step procedures for the synthesis of 5-phenyl-, 6-phenyl- and 7-phenyl-2-amino-[1,2,4]triazolo[1,5-a]pyrimidines, and 2-amino-5-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol has been developed. Two analogs having the Et carboxylate moiety at the C-2 position of the TZP were also prepared in good yields. Then, the scaffolds herein synthesized and two previous scaffolds were functionalized and evaluated for their anti-IAV activity, leading to the identification of compound 2-(5-Methyl-7-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4H-benzo[d][1,3]oxazin-4-one that showed both anti-PA-PB1 (IC50 = 19.5μM) and anti-IAV activity (EC50 = 16μM) at non-toxic concentrations, thus resulting among the most active TZP derivatives reported to date by us. A selection of the synthesized compounds, along with a set of inhouse available analogs, was also tested against SARS-CoV-2. The most promising compound N-(2-Fluorophenyl)-7-methyl-5-phenyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxamide from this series displayed an EC50 value of 34.47μM, highlighting the potential of the TPZ scaffold in the search for anti-CoV agents.

European Journal of Medicinal Chemistry published new progress about Antiviral agents. 1455-77-2 belongs to class isoquinoline, name is 3,5-Diamino-1,2,4-triazole, and the molecular formula is C2H5N5, HPLC of Formula: 1455-77-2.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Pismataro, Maria Chiara published the artcile1,2,4-Triazolo[1,5-a]pyrimidines: Efficient one-step synthesis and functionalization as influenza polymerase PA-PB1 interaction disruptors, Safety of 3,5-Diamino-1,2,4-triazole, the main research area is triazolopyrimidine preparation antiviral influenza polymerase PA PB1 interaction disruptor; 1,2,4-triazolo[1,5-a]pyrimidines; Antiviral agents; Influenza polymerase; Influenza virus; PA-PB1 interaction; Protein-protein interaction; SARS-CoV-2.

In the search for new anti-influenza virus (IV) compounds, the 1,2,4-triazolo[1,5-a]pyrimidine (TZP) was identified as a very suitable scaffold to obtain compounds able to disrupt IV RNA-dependent RNA polymerase (RdRP) PA-PB1 subunits heterodimerization. To this aim, four facile and efficient one-step procedures for the synthesis of 5-phenyl-, 6-phenyl- and 7-phenyl-2-amino-[1,2,4]triazolo[1,5-a]pyrimidines, and 2-amino-5-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol has been developed. Two analogs having the Et carboxylate moiety at the C-2 position of the TZP were also prepared in good yields. Then, the scaffolds herein synthesized and two previous scaffolds were functionalized and evaluated for their anti-IAV activity, leading to the identification of compound 2-(5-Methyl-7-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4H-benzo[d][1,3]oxazin-4-one that showed both anti-PA-PB1 (IC50 = 19.5μM) and anti-IAV activity (EC50 = 16μM) at non-toxic concentrations, thus resulting among the most active TZP derivatives reported to date by us. A selection of the synthesized compounds, along with a set of inhouse available analogs, was also tested against SARS-CoV-2. The most promising compound N-(2-Fluorophenyl)-7-methyl-5-phenyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxamide from this series displayed an EC50 value of 34.47μM, highlighting the potential of the TPZ scaffold in the search for anti-CoV agents.

European Journal of Medicinal Chemistry published new progress about Antiviral agents. 1455-77-2 belongs to class isoquinoline, name is 3,5-Diamino-1,2,4-triazole, and the molecular formula is C2H5N5, Safety of 3,5-Diamino-1,2,4-triazole.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Zima, Vaclav published the artcileInvestigation of flexibility of neuraminidase 150-loop using tamiflu derivatives in influenza A viruses H1N1 and H5N1, COA of Formula: C8H11NO, the main research area is influenza A virus H1N1 H5N1 neuraminidase 150 loop antiviral; tamiflu oseltamivir crystal structure; Click chemistry; Crystal structure; Influenza neuraminidase; Oseltamivir.

This study focuses on design, synthesis and in vitro evaluation of inhibitory potency of two series of sialylmimetic that target an exosite (“”150-cavity””) adjacent to the active site of influenza neuraminidases from A/California/07/2009 (H1N1) pandemic strain and A/chicken/Nakorn-Patom/Thailand/CU-K2-2004 (H5N1). The structure-activity anal. as well as 3-D structure of the complex of parental compound with the pandemic neuraminidase p09N1 revealed high flexibility of the 150-cavity towards various modification of the neuraminidase inhibitors. Furthermore, our comparison of two methods for inhibition constant determination performed at slightly different pH values suggest that the exptl. conditions of the measurement could dramatically influence the outcome of the anal. in the compound-dependent manner. Therefore, previously reported Ki values determined at non-physiol. pH should be carefully scrutinized.

Bioorganic & Medicinal Chemistry published new progress about Antiviral agents. 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, COA of Formula: C8H11NO.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Ilyina, Irina V. published the artcileInfluenza antiviral activity of F- and OH-containing isopulegol-derived octahydro-2H-chromenes, COA of Formula: C9H10O3, the main research area is fluoro hydroxy octahydrochromene preparation isopulegol Prins influenza treatment; Antiviral; Chromene; Fluorine; Influenza; Monoterpene.

The authors synthesized fluoro- and hydroxy-containing octahydro-2H-chromenes by the Prins reaction starting from a monoterpenoid (-)-isopulegol and a wide range of aromatic aldehydes in the presence of the BF3•Et2O/H2O system acting as both an acid catalyst and a fluorine source. Activity of the produced compounds against the influenza A/Puerto Rico/8/34 (H1N1) virus was studied. The highest activity was demonstrated by fluoro- and hydroxy-containing derivatives of 2,4,6-trimethoxybenzaldehyde. The most pronounced virus-inhibiting effect of compounds 10i and 11i was observed at an early stage of infection. These compounds were supposed to be capable of binding to viral hemagglutinin, which is an agreement with data on the effect of compounds 10i and 11i on the viral fusogenic activity as well as by mol. docking studies.

Bioorganic & Medicinal Chemistry Letters published new progress about Antiviral agents. 86-51-1 belongs to class isoquinoline, name is 2,3-Dimethoxybenzaldehyde, and the molecular formula is C9H10O3, COA of Formula: C9H10O3.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Plewe, Michael B. published the artcileSAR studies of 4-acyl-1,6-dialkylpiperazin-2-one arenavirus cell entry inhibitors, Quality Control of 104-01-8, the main research area is acyl dialkyl piperazinone preparation structure arenavirus cell entry inhibitor; Arenavirus; Entry inhibitor; Junin; Lassa; Machupo; Piperazinone.

Old World (Africa) and New World (South America) arenaviruses are associated with human hemorrhagic fevers. Efforts to develop small mol. therapeutics have yielded several chem. series including the 4-acyl-1,6-dialkylpiperazin-2-ones. Herein, we describe an extensive exploration of this chemotype. In initial Phase I studies, R1 and R4 scanning libraries were assayed to identify potent substituents against Old World (Lassa) virus. In subsequent Phase II studies, R6 substituents and iterative R1, R4 and R6 substituent combinations were evaluated to obtain compounds with improved Lassa and New World (Machupo, Junin, and Tacaribe) arenavirus inhibitory activity, in vitro human liver microsome metabolic stability and aqueous solubility

Bioorganic & Medicinal Chemistry Letters published new progress about Antiviral agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Quality Control of 104-01-8.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Si, Dongjuan published the artcileDesign, synthesis and biological evaluation of novel pyrrolidone-based derivatives as potent p53-MDM2 inhibitors, COA of Formula: C9H10O3, the main research area is pyrrolidone derivative design synthesis antitumor activity; p53 MDM2 inhibitor pyrrolidone derivative structure activity relationship; Chalcone; Virtual screening; p53-MDM2; p53-MDM2 inhibitors; pyrrolidone.

Inhibition of the interactions of the tumor suppressor protein p53 with its neg. regulators MDM2 in vitro and in vivo, representing a valuable therapeutic strategy for cancer treatment. The natural product chalcone exhibited moderate inhibitory activity against MDM2, thus based on the binding mode between chalcone and MDM2, a hit unsaturated pyrrolidone scaffold was obtained through virtual screening. Several unsaturated pyrrolidone derivatives were synthesized and biol. evaluated. As a result, because the three critical hydrophobic pockets of MDM2 were occupied by the substituted-Ph linked at the pyrrolidone fragment, compound I demonstrated good binding affinity with the MDM2. Addnl., compound I also showed excellent antitumor activity and selectivity, and no cytotoxicity against normal cells in vitro. The further antitumor mechanism studies were indicated that compound I could successfully induce the activation of p53 and corresponding downstream p21 proteins, thus successfully causing HCT116 cell cycle arrest in the G1/M phase and apoptosis. Thus, the novel unsaturated pyrrolidone p53-MDM2 inhibitors could be developed as novel antitumor agents.

Bioorganic Chemistry published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, COA of Formula: C9H10O3.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Wang, Guangcheng published the artcileDesign, synthesis, molecular modeling, and biological evaluation of pyrazole-naphthalene derivatives as potential anticancer agents on MCF-7 breast cancer cells by inhibiting tubulin polymerization, Category: isoquinoline, the main research area is pyrazole naphthalene preparation docking anticancer human tubulin polymerization inhibition; Anticancer; Naphthalene; Pyrazole; Tubulin polymerization inhibitor.

A new series of pyrazole-naphthalene derivatives I (R = 4-Me, 3-MeO, 4-EtO, etc.) have been synthesized and evaluated for their anticancer activity against human breast cancer cell lines (MCF-7). Most of newly synthesized compounds, except I (R = 3,4-(MeO)2, 4-F, 3-Cl) exhibited potent antiproliferative activity in the range of IC50 = 2.78 +/- 0.24μM – 9.13 +/- 0.47μM. Among them, compound I (R = 4-EtO) (IC50 = 2.78 +/- 0.24μM), bearing ethoxy at the 4-position of the Ph ring, was found to be the most active compound in this series of compounds, with five folds more active than the standard drug cisplatin (IC50 = 15.24 +/- 1.27μM). In addition, compound I (R = 4-EtO) and colchicine showed the same ability to inhibit tubulin polymerization with the IC50 values of 4.6μM and 6.7μM, resp. Cellular mechanism studies elucidated that compound I (R = 4-EtO) arrested the cell cycle at G2/M phase and induced apoptosis. Furthermore, mol. docking anal. revealed that compound I (R = 4-EtO) formed stable interactions in the colchicine-binding site of tubulin.

Bioorganic Chemistry published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Category: isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Wang, Guangcheng published the artcileDesign, synthesis and biological evaluation of isoxazole-naphthalene derivatives as anti-tubulin agents, Quality Control of 104-01-8, the main research area is isoxazole naphthalenyl preparation antitumor activity mol docking.

In this study, a novel series of isoxazole-naphthalene hybrids I [R = 2-ClC6H4, 4-EtOC6H4, 3,4,5-(MeO)3C6H2, 2H-1,3-benzodioxol-5-yl, etc.] as tubulin polymerization inhibitors were designed, synthesized and evaluated for their anti-proliferative activities against human breast cancer cell line MCF-7. Most of the synthesized compounds I exhibited moderate to potent antiproliferative activity (IC50 < 10.0μM), as compared to cisplatin (15.24 ± 1.27μM). Among them, compound I (R = 4-EtOC6H4) was found to be the most active compound with IC50 value of 1.23 ± 0.16μM. Mechanistic studies revealed that this compound arrested cell cycle at G2/M phase and induced apoptosis. Furthermore, in vitro tubulin polymerization assay showed that the compound I (R = 4-EtOC6H4) displayed better inhibition activity on tubulin polymerization (IC50 = 3.4μM) than colchicine (IC50 = 7.5μM). Mol. docking study also revealed that this compound binds to the colchicine binding site of tubulin. Arabian Journal of Chemistry published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Quality Control of 104-01-8.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Jadhav, Bhagwat S. published the artcileSynthesis and In-silico Identification of New Bioactive 1,3,4-oxadiazole Tagged 2,3-dihydroimidazo[1,2-a]pyridine Derivatives, Quality Control of 104-01-8, the main research area is oxadiazolyl imidazopyridine mycobacterium tuberculosis antitumor human mol docking.

A set of five new 1,3,4-oxadiazolyl-imidazo-1,2-pyridine derivatives I (R = Bn, 2-ClC6H4CH2, 4-MeOC6H4, etc.) was synthesized and screened in-vitro for their antibacterial activity against Mycobacterium tuberculosis (H37 RV strain) ATCC No-27294. Results: Compound I (R = 2-ClC6H4CH2) displayed potent antitubercular activity at MIC 6.25μg/mL. In-silico mol. docking studies were performed for the evaluation of the binding patterns of compounds I in the binding site of proteins like, Pantothenate synthatase and enoyl acyl reductase inhibitor. The outcomes of the in-vitro antitubercular studies were in good agreement with the mol. docking studies. These newly synthesized compounds were found to have a good ADMET profile. Authors also explored possible anticancer activity using in-silico methods. These results show that readily synthesized 1,3,4-oxadiazolyl-imidazo-1,2-pyridine derivatives I are attracting a new class of potent anti-TB targets as well as possible anticancer activity that worth addnl. opportunities for improvements.

Current Bioactive Compounds published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Quality Control of 104-01-8.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Lacova, Margita published the artcileA novel and efficient synthesis of 3-aryl-5-(2-hydroxybenzoyl)pyridin-2(1H)-ones by re-cyclization of N-(oxopyranochromenyl)acetamides and their antineoplastic screening, Category: isoquinoline, the main research area is pyridinone preparation oxopyranochromenyl acetamide recyclization antitumor human.

A novel, simple and efficient methodol. for preparation of yet unknown 3-aryl-5-(2-hydroxybenzoyl)pyridin-2(1H)-ones I (R = H, 9-Me, 9-NO2, 8,9-(Me)2; Ar = Ph, 4-MeO, 4-NO2, 1H-tetrazole) by EtONa driven re-cyclization of N-(3-aryl-2-oxo-2,5-dihydropyrano[3,2-c]chromen-5-yl)acetamides II in good yields (80-95%) is reported. The 3-aryl-2-oxo-2,5-dihydropyrano[3,2-c]chromen-5-yl acetates III were prepared by cyclocondensation of 3-formylchromones (4-oxo-4H-chromene-3-carbaldehydes) and acetic acids in 64-86% yields. Acetamides II were obtained by reaction of 3-aryl-2-oxo-2,5-dihydropyrano[3,2-c]chromen-5-yl acetates III with AcNH2 catalyzed by p-TsOH in 80-93% yields. Click chem. precursors were prepared by propargylation of pyridones in 92-98% yields. They can serve for construction of more complex mols. possessing pyridone skeleton. Eleven novel compounds were screened for their anticancer activity on a panel of human tumor cell lines by NCI USA. These compounds selectively inhibit the growth of some of the tumor cell lines at 10-5 M (up to -33% compared to a control). The most sensitive tumor cell lines originated from kidney, breast, skin, ovary, blood and lung.

Chemical Papers published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Category: isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem