Month: February 2023

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

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

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