Heterocyclic Building Blocks-phthalazine

Possibility of new molecular-targeted therapy from the perspective of GIST treatment resistant examples was written by Niimura, Takeshi;Suzuki, Hiromu;Shinomura, Yasuhisa. And the article was included in Bunshi Shokakibyo in 2012.Related Products of 212141-54-3 This article mentions the following:

Imatinib mesilate (imatinib), sunitinib malate (sunitinib) are being used as a drug treatment against Gastrointestinal stromal tumor (GIST) but some cases having resistance against these drugs have also been appeared. Imatinib resistance includes a primary resistance wherein an effect is considered to be less from the beginning and a secondary resistance due to acquisition of new genetic mutation. The mechanism of sunitinib resistance is not completely understood; however, autonomous activation of KIT due to the mutation of activation loop and decrease in the development of PTEN due to the methylation of promoter area and activation of Akt path etc. have been reported. A medical treatment using multi-target Tyrosine kinase such as Nilotinib hydrochloride which is the new tyrosine kinase inhibitor against imatinib, sunitinib resistance cases, inhibitors of intracellular signal transmission path such a mTOR, sorafenib tosilate that targets both of the Tyrosine kinase and intracellular signal transmission mols. is being considered. In addition, the drugs targeting the mols. such as heat shock protein (Hsp) 90 which are involved in the tumor formation are being considered as medical treatment target and clin. trials are also in progress. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3Related Products of 212141-54-3).

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 antimicrobial, antidiabetic, analgesic, anticonvulsant, antitumor, antiproliferative, antiepileptic, anti-inflammatory, and vasorelaxant. Both pyridazine and phthalazine give rise to very good TREPR signals in rigid media at low temperatures.Related Products of 212141-54-3

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

AutoT&T v.2: An Efficient and Versatile Tool for Lead Structure Generation and Optimization was written by Li, Yan;Zhao, Zhixiong;Liu, Zhihai;Su, Minyi;Wang, Renxiao. And the article was included in Journal of Chemical Information and Modeling in 2016.Synthetic Route of C20H15ClN4 This article mentions the following:

In structure-based drug design, automated de novo design methods are helpful tools for lead discovery as well as lead optimization. In a previous study the authors reported a new de novo design method, namely, Automatic Tailoring and Transplanting (AutoT&T). It overcomes some intrinsic problems in conventional fragment-based buildup methods. In this study, the authors describe an upgraded version, namely, AutoT&T2. Structural operations conducted by AutoT&T2 have been largely optimized by introducing several new algorithms. As a result, its overall speed in multiround optimization jobs has been improved by a few thousand fold. With this improvement, it is now practical to conduct structural crossover among multiple lead mols. using AutoT&T2. Three different test cases are described in this study that demonstrate the new features and versatile applications of AutoT&T2. The AutoT&T2 software suite is available to the public. Besides, a Web portal for running AutoT&T2 online is provided at http://www.sioc-ccbg.ac.cn/software/att2 for testing. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3Synthetic Route of C20H15ClN4).

N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3) belongs to phthalazine derivatives. Although, N-containing heterocyclic compounds are widely distributed in nature, the presence of two adjacent nitrogen atoms in the phthalazine ring makes it rare and not very familiar in isolated extracts from living organisms. 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.Synthetic Route of C20H15ClN4

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

Spectra and structure of derivatives of p-dihydroxypyridazine and phthalazine was written by Cheinker, Yu. N.;Gortinskaya, T. V.;Sycheva, T. P.. And the article was included in Journal de Chimie Physique et de Physico-Chimie Biologique in 1958.Reference of 18393-54-9 This article mentions the following:

IR and UV spectra of the dihydroxy derivatives of pyridazine and phthalazine, as well as their Me and Cl derivatives, were studied with a view to establishing the structure of the dihydroxy derivatives It was concluded that the compounds have mixed hydroxyoxo structures, both in the crystalline state and in solution Mols. of 3-hydroxy-6-pyridazine (I), as well as the 1-Me derivative, form chains in the crystalline state, in which each mol. is linked to 2 others by very stable H bonds. The H-bonds in 1-hydroxy-4-phthalazinone (II) do not lead to such chain formation in the crystalline state. The heats of fusion, solubility, and acidity of I, II, and derivatives are consistent with the proposed structures. IR spectra of the following compounds are given between 20 and 14 μ: 1,2-dimethyl-3,6-pyridazinedione, I, 3,6-dimethoxypyridazine, 1-methyl-3-methoxy-6-pyridazinone, 3-methoxy-6-pyridazinone, 1-methyl-3-hydroxy-6-pyridazinone, 2,3-dimethyl-1,4-phthalazinedione II, 1-methoxy-4-phthalazinone, 1-methoxy-4-chlorophthalazine, 3-chloro-6-pyridazinone, 3,6-dichloropyridazine, 3,6-bis(methylthio)pyridazine, 3-mercapto-6-thiopyridazinone, all in the crystalline state; also UV spectra in alc. 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. Phthalazine is isomeric with other naphthyridines including quinoxaline, cinnoline and quinazoline. 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

Stomatitis and VEGFR-tyrosine kinase inhibitors (VR-TKIs): a review of current literature in 4369 patients was written by Arena, Claudia;Troiano, Giuseppe;De Lillo, Alfredo;Testa, Nunzio F.;Lo Muzio, Lorenzo. And the article was included in BioMed Research International in 2018.COA of Formula: C20H15ClN4 This article mentions the following:

Background. Multitargeted tyrosine kinase inhibitors (TKIs) represent a new class of target-specific antineoplastic agents. These agents show some specific adverse events such as fatigue/asthenia, anorexia/loss of appetite, dysgeusia, diarrhea/abdominal pain, hypothyroidism, hypertension, myelosuppression, and stomatitis. Materials and Methods. A systematic search was performed on PubMed online database using a combination of MESH terms and free text words, “sunitinib” OR “sorafenib” OR “axitinib” OR “cabozantinib” OR “pazopanib” OR “regorafenib” OR “nintedanib” OR “vatalanib” combined through the use of Boolean operator AND with the key words”stomatitis” OR “mucositis,” (i) on human subjects, (ii) written in the English language, and (iii) reporting about the incidence of stomatitis or oral mucositis. Results.. The incidence of stomatitis of any grade was 35.2% for sunitinib, 20.52% for sorafenib, 20.63% for axitinib, and 34.21% for cabozantinib. All the agents showed high rates of lowgrade stomatitis (G1-G2), while the onset of severe stomatitis (G3-G4) was very low. Conclusions. Anal. of the reports with patients treated with sunitinib, sorafenib, axitinib, and cabozantinib showed a clear prevalence of stomatitis grade 1 or grade 2. These data differ from those of patients treated with conventional chemotherapy in which mucositis is predominantly of grade 3 or grade 4. 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 and phthalazinone derivatives are important owing to their significant biological activities and pharmacological properties. 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

Cleavage of phthaloylglycine by substituted hydrazines was written by Rosenthal, Arthur F.. And the article was included in Journal of Organic Chemistry in 1957.COA of Formula: C9H8N2O2 This article mentions the following:

Refluxing 1.8 g. 2,5-dichlorophenylhydrazine, 1.03 g. phthaloylglycine (I), and 0.93 g. Bu₃N in 5 cc. 95% EtOH 12 hrs. on a steam bath, adding 15 cc. Me₂CO, refluxing the mixture another 15 min., evaporating the filtered solution in vacuo, taking up the residue in 15 cc. Et₂O, treating the Et₂O solution 1 min. with HCl, and evaporating the Et₂O give 40% N-(2,5-dichlorophenyl)phthalhydrazide, faintly yellow crystals, m. 204-5°. Refluxing 1.03 g. I, 1.85 g. Bu₃N, and MeNHNH₂ from 1.44 g. sulfate 20 hrs. in 30 cc. 95% EtOH, evaporating the mixture to 1/3 its volume, adding 40 cc. EtCOMe, refluxing the mixture 15 min., filtering off 346 mg. glycine, evaporating the filtrate, and adding 40 cc. Et₂O and 100 cc. C₅H₁₂ give 88% N-methylphthalhydrazide, m. 238.5-9.5° (N-acetyl-N’-methylphthalhydrazide, m. 139.5-40.5°). In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9COA of Formula: C9H8N2O2).

2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9) belongs to phthalazine derivatives.Like many other isomeric benzodiazines, phthalazine derivatives reveal numerous pharmacological and biological activities such as analgesic, anticonvulsant, antitumor, antiproliferative. In addition, phthalazines are known as serotonin reuptake inhibitors and are considered as anti-depression agents.COA of Formula: C9H8N2O2

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

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

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

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

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