Category: phthalazine

Synergism of imatinib, vatalanib and everolimus in the prevention of chronic lung allograft rejection after lung transplantation (LTx) in rats was written by Keil, Laura;Schaub, Anna-Lena;Hirt, Stephan W.;Schmid, Christof;Lehle, Karla;von Suesskind-Schwendi, Marietta. And the article was included in Histology and Histopathology in 2019.Reference of 212141-54-3 This article mentions the following:

Chronic lung allograft dysfunction (CLAD) still remains a major drawback in the outcome following lung transplantation (LTx). New therapeutic strategies are warranted. Growth factors and their receptors like platelet-derived growth factor-receptor (PDGFR) and vascular endothelial growth factor-receptor (VEGFR), may play a crucial role in the development of CLAD, especially bronchiolitis obliterans (BO) and vasculopathy. In this study, we used an orthotopic left lung transplantation model from Fischer (F344) to Wystar Kyoto (WKY) rats to investigate the effect of the receptor tyrosine kinase inhibitor (RTKI) vatalanib alone, the dual combination of the RTKIs vatalanib and imatinib and a triple therapy consisting of vatalanib, imatinib and the mammalian target of rapamycin inhibitor (mTORI) everolimus on the development of CLAD after LTx in rats. With this trial we demonstrated that monotherapy with vatalanib attenuated mild and severe chronic vascular rejection, whereas dual therapy (vatalanib and imatinib) after LTx also showed a significant reduction of chronic bronchiolar rejection and interstitial fibrosis. By adding everolimus, the effect of vatalanib and imatinib could addnl. be increased. In conclusion, the combination of mTORI and RTKIs might be a possible strategy in the prevention of CLAD and BO. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3Reference of 212141-54-3).

N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3) belongs to phthalazine derivatives. Phthalazine is isomeric with other naphthyridines including quinoxaline, cinnoline and quinazoline. Both pyridazine and phthalazine give rise to very good TREPR signals in rigid media at low temperatures.Reference of 212141-54-3

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

Gefitinib and afatinib show potential efficacy for Fanconi anemia-related head and neck cancer was written by Montanuy, Helena;Martinez-Barriocanal, Agueda;Casado, Jose Antonio;Rovirosa, Llorenc;Ramirez, Maria Jose;Nieto, Rocio;Carrascoso-Rubio, Carlos;Riera, Pau;Gonzalez, Alan;Lerma, Enrique;Lasa, Adriana;Carreras-Puigvert, Jordi;Helleday, Thomas;Bueren, Juan A.;Arango, Diego;Minguillon, Jordi;Surralles, Jordi. And the article was included in Clinical Cancer Research in 2020.Reference of 212141-54-3 This article mentions the following:

In this work, we searched and validated two already approved drugs as new potential therapies for HNSCC in patients with Fanconi anemia. We conducted a high-content screening of 3,802 drugs in a FANCA-deficient tumor cell line to identify nongenotoxic drugs with cytotoxic/cytostatic activity. The best candidates were further studied in vitro and in vivo for efficacy and safety. Results: Several FDA/European Medicines Agency (EMA)-approved anticancer drugs showed cancer-specific lethality or cell growth inhibition in Fanconi anemia HNSCC cell lines. The two best candidates, gefitinib and afatinib, EGFR inhibitors approved for non-small cell lung cancer (NSCLC), displayed nontumor/tumor IC50 ratios of approx. 400 and approx. 100 times, resp. Neither gefitinib nor afatinib activated the Fanconi anemia signaling pathway or induced chromosomal fragility in Fanconi anemia cell lines. Importantly, both drugs inhibited tumor growth in xenograft experiments in immunodeficient mice using two Fanconi anemia patient-derived HNSCCs. Finally, in vivo toxicity studies in Fanca-deficient mice showed that administration of gefitinib or afatinib was well-tolerated, displayed manageable side effects, no toxicity to bone marrow progenitors, and did not alter any hematol. parameters. Conclusions: Our data present a complete preclin. anal. and promising therapeutic line of the first FDA/EMA-approved anticancer drugs exerting cancer-specific toxicity for HNSCC in patients with Fanconi anemia. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3Reference of 212141-54-3).

N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3) belongs to phthalazine derivatives. Phthalazines, as an important class of bicyclic N-heterocycles, have attracted sizable attention due to their valuable biological and pharmacological activities. New methods for the functionalization of pyridazine, phthalazine, and cinnoline rings emerged in 2016. Buchwald and his group devised an asymmetric hydroarylation of vinylarenes.Reference of 212141-54-3

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

Medical treatment of recurrent meningiomas was written by Chamberlain, Marc C.;Barnholtz-Sloan, Jill S.. And the article was included in Expert Review of Neurotherapeutics in 2011.Application In Synthesis of N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine This article mentions the following:

Meningiomas are the second most common primary brain tumor and are primarily treated with surgery (with or without embolization) and radiotherapy. Increasingly today, meningiomas undergo multiple resections and two radiotherapy treatments (either stereotactic or conventional external beam) before consideration for hormonal, chemotherapy or targeted therapy. The failure of hormonal and cytotoxic chemotherapy in the treatment of recurrent meningioma and increasing understanding of potential mol. targets in meningioma has resulted in multiple studies utilizing single-agent targeted therapy directed at biol. relevant signaling pathways, such as somatostatin (Sandostatin LAR, SOM230c), PDGF (imatinib), EGF (erlotinib) and VEGF (sunitinib and vatalanib). Early results using a targeted approach have been modest at best and are often associated with significant toxicity. Consequently and at present, the brain tumor guidelines recognize only three medical therapies for inoperable and radiation-refractory meningiomas: hydroxyurea, IFN-α and Sandostatin LAR, a somatostatin analog. Clearly, there remains an unmet need in neuro-oncol. with respect to the medical treatment of recurrent meningiomas. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3Application In Synthesis of N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine).

N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3) belongs to phthalazine derivatives. Pyridazine and phthalazine have quite different spectroscopic properties compared with their isomers, pyrazine and quinoxaline. Phthalazine derivatives are also considered as p38MAP kinase inhibitors, selective binders of gamma-aminobutyric acid (GABA) receptors, cyclooxygenase-2 (COX-2) inhibitors, and high-affinity ligands of voltages gated calcium channels.Application In Synthesis of N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

A phase I study of the vascular endothelial growth factor inhibitor Vatalanib in combination with Pemetrexed disodium in patients with advanced solid tumors was written by Wang, Fen;Molina, Julian;Satele, Daniel;Yin, Jun;Lim, Vun-Sin;Adjei, Alex A.. And the article was included in Investigational New Drugs in 2019.Name: N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine This article mentions the following:

Introduction Vatalanib is an oral receptor tyrosine kinase inhibitor that blocks all known VEGF, PDGF, and c-Kit receptors. This phase I study evaluated the safety, tolerability, and biol. activity of the combination of vatalanib with pemetrexed disodium in patients with advanced solid tumors. Methods Patients were administered escalating twice daily doses of vatalanib in combination with pemetrexed disodium in 21-day cycles. A dose expansion cohort was enrolled to further define the maximum tolerated dose (MTD) and further evaluate efficacy. Results A total of 29 patients were enrolled in the study (dose escalation, 9; dose expansion, 20). Dose-limiting toxicities included grade 4 thrombocytopenia (6.9%) and febrile neutropenia, anorexia, constipation, and dehydration. Other common adverse events were fatigue (75%), nausea (66%), vomiting (48%), oral mucositis (31%) and diarrhea (28%). The majority of these toxicities were Grade 1-2. The MTD was reached at vatalanib 250 mg twice daily continuously combined with pemetrexed disodium 500 mg/m² day 1. Overall, 2 patients (6.9%) had partial responses, 8 (27.6%) had stable disease for at least 4 cycles, 5 had progressive disease (17.2%) and 5 went off study before disease assessment. Conclusion The combination of vatalanib with pemetrexed disodium was feasible, but not well tolerated. The modest efficacy results are consistent with other results obtained from combinations of chemotherapy and a large number of VEGF tyrosine kinase inhibitors. This combination should not be developed further unless predictive biomarkers can be identified. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3Name: N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine).

N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3) belongs to phthalazine derivatives.Like many other isomeric benzodiazines, phthalazine derivatives reveal numerous pharmacological and biological activities such as analgesic, anticonvulsant, antitumor, antiproliferative. As with cinnolines, phthalazines were also prepared most frequently through condensations of hydrazine derivatives and carbonyl-containing compounds.Name: N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

Virtual Target Screening: Validation Using Kinase Inhibitors was written by Santiago, Daniel N.;Pevzner, Yuri;Durand, Ashley A.;Tran, MinhPhuong;Scheerer, Rachel R.;Daniel, Kenyon;Sung, Shen-Shu;Woodcock, H. Lee III;Guida, Wayne C.;Brooks, Wesley H.. And the article was included in Journal of Chemical Information and Modeling in 2012.Recommanded Product: N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine This article mentions the following:

Computational methods involving virtual screening could potentially be employed to discover new biomol. targets for an individual mol. of interest (MOI). However, existing scoring functions may not accurately differentiate proteins to which the MOI binds from a larger set of macromols. in a protein structural database. An MOI will most likely have varying degrees of predicted binding affinities to many protein targets. However, correctly interpreting a docking score as a hit for the MOI docked to any individual protein can be problematic. In our method, which we term “Virtual Target Screening (VTS)”, a set of small drug-like mols. are docked against each structure in the protein library to produce benchmark statistics. This calibration provides a reference for each protein so that hits can be identified for an MOI. VTS can then be used as tool for: drug repositioning (repurposing), specificity and toxicity testing, identifying potential metabolites, probing protein structures for allosteric sites, and testing focused libraries (collection of MOIs with similar chemotypes) for selectivity. To validate our VTS method, twenty kinase inhibitors were docked to a collection of calibrated protein structures. Here, we report our results where VTS predicted protein kinases as hits in preference to other proteins in our database. Concurrently, a graphical interface for VTS was developed. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3Recommanded Product: N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine).

N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3) belongs to phthalazine derivatives.Like many other isomeric benzodiazines, phthalazine derivatives reveal numerous pharmacological and biological activities such as analgesic, anticonvulsant, antitumor, antiproliferative. As with cinnolines, phthalazines were also prepared most frequently through condensations of hydrazine derivatives and carbonyl-containing compounds.Recommanded Product: N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

Biological active acylhydrazide I. The O-acyl derivatives nature of monoacylation products of cyclic maleic- and phthalic-hydrazide was written by Panea, I.;Bodochi, Lucia;Panea, Teodora;Zinveliu, Daniela;Pascalau, Violeta. And the article was included in Southern Brazilian Journal of Chemistry in 1999.Reference of 18393-54-9 This article mentions the following:

It was confirmed, on the basis of chem. and physico-chem. (m.ps., IR and ¹H-NMR spectra) data, that the products formed by monoacylation of cyclic maleic and phthalic acid hydrazides are the O-acyl derivatives, although owing to tautomerism, these hydrazides may form N- or/and O-acyl derivatives in such reactions. Simultaneously, it was shown that claims of formation of N-acyl derivatives of cyclic maleic and phthalic acid hydrazides were not valid. Also by reacting the cyclic maleic and phthalic acid hydrazide with 4-chlorobenzoyl chloride two new O-monoacyl derivatives [3-(4-chlorobenzoyloxy)-1-H-pyridazin-6-one and 1-(4-chlorobenzoyloxy)-3-H-phthalazin-1-one] were obtained. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9Reference of 18393-54-9).

2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9) belongs to phthalazine derivatives. Phthalazines, as an important class of bicyclic N-heterocycles, have attracted sizable attention due to their valuable biological and pharmacological activities. New methods for the functionalization of pyridazine, phthalazine, and cinnoline rings emerged in 2016. Buchwald and his group devised an asymmetric hydroarylation of vinylarenes.Reference of 18393-54-9

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

Cell Panel Profiling Reveals Conserved Therapeutic Clusters and Differentiates the Mechanism of Action of Different PI3K/mTOR, Aurora Kinase and EZH2 Inhibitors was written by Uitdehaag, Joost C. M.;de Roos, Jeroen A. D. M.;Prinsen, Martine B. W.;Willemsen-Seegers, Nicole;de Vetter, Judith R. F.;Dylus, Jelle;van Doornmalen, Antoon M.;Kooijman, Jeffrey;Sawa, Masaaki;van Gerwen, Suzanne J. C.;de Man, Jos;Buijsman, Rogier C.;Zaman, Guido J. R.. And the article was included in Molecular Cancer Therapeutics in 2016.COA of Formula: C20H15ClN4 This article mentions the following:

Cancer cell line panels are important tools to characterize the in vitro activity of new investigational drugs. Here, we present the inhibition profiles of 122 anticancer agents in proliferation assays with 44 or 66 genetically characterized cancer cell lines from diverse tumor tissues (Oncolines). The library includes 29 cytotoxics, 68 kinase inhibitors, and 11 epigenetic modulators. For 38 compounds this is the first comparative profiling in a cell line panel. By strictly maintaining optimized assay protocols, biol. variation was kept to a min. Replicate profiles of 16 agents over three years show a high average Pearson correlation of 0.8 using IC₅₀ values and 0.9 using GI₅₀ values. Good correlations were observed with other panels. Curve fitting appears a large source of variation. Hierarchical clustering revealed 44 basic clusters, of which 26 contain compounds with common mechanisms of action, of which 9 were not reported before, including TTK, BET and two clusters of EZH2 inhibitors. To investigate unexpected clusterings, sets of BTK, Aurora and PI3K inhibitors were profiled in biochem. enzyme activity assays and surface plasmon resonance binding assays. The BTK inhibitor ibrutinib clusters with EGFR inhibitors, because it cross-reacts with EGFR. Aurora kinase inhibitors sep. into two clusters, related to Aurora A or pan-Aurora selectivity. Similarly, 12 inhibitors in the PI3K/AKT/mTOR pathway separated into different clusters, reflecting biochem. selectivity (pan-PI3K, PI3Kβγδ-isoform selective or mTOR-selective). Of these, only allosteric mTOR inhibitors preferentially targeted PTEN-mutated cell lines. This shows that cell line profiling is an excellent tool for the unbiased classification of antiproliferative compounds Mol Cancer Ther; 15(12); 3097-109. ©2016 AACR. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3COA of Formula: C20H15ClN4).

N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3) belongs to phthalazine derivatives. Phthalazine is isomeric with other naphthyridines including quinoxaline, cinnoline and quinazoline. As with pyridazines, phthalazines, the other benzopyridazines, were also prepared most frequently through the condensation of hydrazines with carbonyl-containing compounds, typically phthalate derivatives. COA of Formula: C20H15ClN4

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem