Category: 212141-54-3

Vatalanib population pharmacokinetics in patients with myelodysplastic syndrome: CALGB 10105 (Alliance) was written by Wang, Xiaofeng;Owzar, Kouros;Gupta, Pankaj;Larson, Richard A.;Mulkey, Flora;Miller, Antonius A.;Lewis, Lionel D.;Hurd, David;Vij, Ravi;Ratain, Mark J.;Murry, Daryl J.;Alliance for Clinical Trials in Oncology. And the article was included in British Journal of Clinical Pharmacology in 2014.Reference of 212141-54-3 This article mentions the following:

Aims : Vatalanib is an oral anti-angiogenesis agent that inhibits vascular endothelial growth factor receptor tyrosine kinases, which in patients showed auto induction of metabolism and variability in pharmacokinetic (PK) disposition. The objective was to characterize the population PK and time-dependent change in vatalanib clearance and assess exposure-toxicity relationship in patients with myelodysplastic syndrome (MDS). Methods : This was an open-label phase II study of vatalanib in MDS patients receiving 750-1250 mg once daily in 28-day cycles. Serial blood samples were obtained and plasma vatalanib concentrations measured by HPLC. Population PK anal. was performed using nonmem 7.2 with FO estimation since FOCE failed. The final model was evaluated using goodness-of-fit plots, bootstrap anal., and visual predictive check. Results : Pharmacokinetic data were complete for 137 patients (86 M, 51 F), of median age 70 years (range 20-91). A one-compartment model with lagged first-order absorption and time-dependent change in oral clearance was fitted to the vatalanib plasma concentration vs. time data. The population means for pre-induction and post-induction oral clearance were 24.1 l h^-1 (range: 9.6-45.5) and 54.9 l h^-1 (range: 39.8-75.6), resp. The apparent oral clearance increased 2.3-fold, (range: 1.7-4.1-fold) from first dose to steady state. Our data did not identify a significant relationship of the predefined covariates with vatalanib pharmacokinetics, although power to detect such a relationship was limited. Conclusions : Vatalanib pharmacokinetics were highly variable and the extent of auto induction was not determined to correlate with any of the pre-defined covariates. 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. Pyridazine and phthalazine have quite different spectroscopic properties compared with their isomers, pyrazine and quinoxaline. As with cinnolines, phthalazines were also prepared most frequently through condensations of hydrazine derivatives and carbonyl-containing compounds.Reference of 212141-54-3

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

Biologically Relevant Chemical Space Navigator: From Patent and Structure-Activity Relationship Analysis to Library Acquisition and Design was written by Rabal, Obdulia;Oyarzabal, Julen. 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:

A new and versatile visualization tool, based on a descriptor accounting for ligand-receptor interactions (LiRIf), is introduced for guiding medicinal chemists in analyzing the R-groups from a congeneric series. Anal. is performed in a reference-independent scenario where the whole biol. relevant chem. space (BRCS) is represented. Using a real project-based data set, the authors show the impact of this tool on four key navigation strategies for the drug discovery process. First, this navigator analyzes competitors’ patents, including a comparison of patents coverage and the identification of the most frequent fragments. Second, the tool analyzes the structure-activity relationship (SAR) leading to the representation of reference-independent activity landscapes that enable the identification not only of critical ligand-receptor interactions (LRI) and substructural features but also of activity cliffs. Third, this navigator enables comparison of libraries, thus selecting com. available mols. that complement unexplored spaces or areas of interest. Finally, this tool also enables the design of new analogs, which is based on reaction types and the exploration purpose (focused or diverse), selecting the most appropriate reagents. 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. Pyridazine and phthalazine have quite different spectroscopic properties compared with their isomers, pyrazine and quinoxaline. 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

Selective Vascular Endothelial Growth Factor Receptor Inhibitors Provide Limited Benefits for Metastatic Colorectal Cancer: A Meta-Analysis was written by Fan, Qin;Lv, Wenhao;Xu, Yuexin;Dong, Yuan;Xiang, Zhiqiang;Wang, Junjie. And the article was included in Current Pharmaceutical Design in 2020.Recommanded Product: N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine This article mentions the following:

Background: Metastatic colorectal cancer (mCRC) is one of the most common and deadly cancers worldwide. For most patients diagnosed with mCRC and managed with 5-fluorouracil (5-FU)/leucovorin plus oxaliplatin (FOLFOX), the median survival time is still less than 2 years. Small mol. selective vascular endothelial growth factor receptor (VEGFR) inhibitors have been demonstrated to have strong anti-tumor activity in various cancer models. Objective: To demonstrate the efficacy and safety of selective VEGFR inhibitors in the management of mCRC. Methods: A comprehensive search in PubMed, EMBASE, Web of Science, Ovid MEDLINE, Google Scholar, Springer and Cochrane Central databases was performed for randomized controlled trials (RCTs) focusing on the effect of selective VEGFR inhibitors on mCRC. The primary outcome measures were progression-free survival (PFS) rates, overall survival (OS) rates, complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rates (ORRs), disease control rates (DCRs) and adverse effect (AE) rates. The dates of the included studies ranged from the inception of the database to Jan. 15, 2020. Results: Twenty-two RCTs were included. A total of 9362 patients met the inclusion criteria. Compared with placebo, selective VEGFR inhibitors significantly increased the PFS rate, SD, PR and DCR, reduced PD, caused more treatment-emergent adverse events (TEAEs), hypertension, hand-foot skin reaction, diarrhoea, fatigue, and thrombocytopaenia and increased aspartate aminotransferase(AST) concentration There was no significant difference between selective VEGFR inhibitors and placebo regarding OS rate, CR, ORR, proteinuria, hyperbilirubinemia or alk. phosphatase(ALP) concentration Addnl., compared with FOLFOX4+placebo, FOLFOX4+ selective VEGFR inhibitors, clearly reduced PD, and caused more 3-4 AEs, serious AEs, hypertension, hand-foot syndrome, diarrhoea, nausea, vomiting, decreased appetite, dehydration, fatigue, dizziness, neutropaenia and thrombocytopaenia. For PFS rate, OS rate, CR, PR, SD, ORR, abdominal pain, peripheral sensory neuropathy, asthaenia, anemia and hypokalemia rates, there was no significant difference between FOLFOX4+ selective VEGFR inhibitors and FOLFOX4+placebo. However, compared with FOLFOX4+bevacizumab, FOLFOX4+selective VEGFR inhibitors, led to increased hypertension, neutropaenia, fatigue, thrombocytopaenia and asthaenia. There is no clear difference between FOLFOX4+selective VEGFR inhibitors and FOLFOX4+ bevacizumab with regard to PFS rate, OS rate, CR, PR, SD, PD, ORR, diarrhoea, nausea, vomiting, peripheral neuropathy and abdominal pain rates. Selective VEGFR inhibitors+cetuximab increased PFS and PR and reduced PD compared to cetuximab, but there was no statistical difference between the two groups for OS and SD. Conclusion: Compared with placebo or cetuximab, selective VEGFR inhibitors alone or combined with cetuximab seemed to be more efficacious for mCRC resp.; however, the effects were not better than FOLFOX4 alone or when combined with bevacizumab for mCRC. Addnl., selective VEGFR inhibitors were not as safe as placebo or FOLFOX4 alone or in combination with bevacizumab in mCRC. 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. Phthalazines, as an important class of bicyclic N-heterocycles, have attracted sizable attention due to their valuable biological and pharmacological activities. Phthalazines are popular pharmacophores as they are the core chemical motifs in many commercially available drugs such as Azelastin (antihistamine), Vatalanib (vascular endothelial growth factor receptor (VEGFR) inhibitor), and Hydralazine (antihypertensive agent).Recommanded Product: N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

Validation of a High-Content Screening Assay Using Whole-Well Imaging of Transformed Phenotypes was written by Ramirez, Christina N.;Ozawa, Tatsuya;Takagi, Toshimitsu;Antczak, Christophe;Shum, David;Graves, Robert;Holland, Eric C.;Djaballah, Hakim. And the article was included in Assay and Drug Development Technologies in 2011.HPLC of Formula: 212141-54-3 This article mentions the following:

Automated microscopy was introduced two decades ago and has become an integral part of the discovery process as a high-content screening platform with noticeable challenges in executing cell-based assays. It would be of interest to use it to screen for reversers of a transformed cell phenotype. In this report, we present data obtained from an optimized assay that identifies compounds that reverse a transformed phenotype induced in NIH-3T3 cells by expressing a novel oncogene, KP, resulting from fusion between platelet derived growth factor receptor alpha (PDGFRα) and kinase insert domain receptor (KDR), that was identified in human glioblastoma. Initial image acquisitions using multiple tiles per well were found to be insufficient as to accurately image and quantify the clusters; whole-well imaging, performed on the IN Cell Analyzer 2000, while still two-dimensional imaging, was found to accurately image and quantify clusters, due largely to the inherent variability of their size and well location. The resulting assay exhibited a Z’ value of 0.79 and a signal-to-noise ratio of 15, and it was validated against known effectors and shown to identify only PDGFRα inhibitors, and then tested in a pilot screen against a library of 58 known inhibitors identifying mostly PDGFRα inhibitors as reversers of the KP induced transformed phenotype. In conclusion, our optimized and validated assay using whole-well imaging is robust and sensitive in identifying compounds that reverse the transformed phenotype induced by KP with a broader applicability to other cell-based assays that are challenging in HTS against chem. and RNAi libraries. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3HPLC of Formula: 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. 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.HPLC of Formula: 212141-54-3

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

In Vitro Angiogenesis Inhibition and Endothelial Cell Growth and Morphology was written by Ljoki, Arlinda;Aslam, Tanzila;Friis, Tina;Ohm, Ragnhild G.;Houen, Gunnar. And the article was included in International Journal of Molecular Sciences in 2022.Name: N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine This article mentions the following:

A co-culture assay with human umbilical vein endothelial cells (HUVECs) and normal human dermal fibroblasts (NHDFs) was used to study whether selected angiogenesis inhibitors were able to inhibit differentiation and network formation of HUVECs in vitro. The effect of the inhibitors was determined by the morphol. and the calculated percentage area covered by HUVECs. Neutralizing VEGF with avastin and polyclonal goat anti-VEGF antibody and inhibiting VEGFR2 with sorafenib and vatalanib resulted in the formation of HUVEC clusters of variable sizes as a result of inhibited EC differentiation. Furthermore, numerous inhibitors of the VEGF signaling pathways were tested for their effect on the growth and differentiation of HUVECs. The effects of these inhibitors did not reveal a cluster morphol., either individually or when combined to block VEGFR2 downstream pathways. Only the addition of N-methyl-p-bromolevamisole revealed a similar morphol. as when targeting VEGF and VEGFR2, meaning it may have an inhibitory influence directly on VEGFR signaling. Addnl., several nuclear receptor ligands and miscellaneous compounds that might affect EC growth and differentiation were tested, but only dexamethasone gave rise to cluster formation similarly to VEGF-neutralizing compounds These results point to a link between angiogenesis, HUVEC differentiation and glucocorticoid receptor activation. 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. 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. 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

CXCR2-Expressing Tumor Cells Drive Vascular Mimicry in Antiangiogenic Therapy-Resistant Glioblastoma was written by Angara, Kartik;Borin, Thaiz F.;Rashid, Mohammad H.;Lebedyeva, Iryna;Ara, Roxan;Lin, Ping-Chang;Iskander, A. S. M.;Bollag, Roni J.;Achyut, Bhagelu R.;Arbab, Ali S.. And the article was included in Neoplasia (New York, NY, United States) in 2018.Reference of 212141-54-3 This article mentions the following:

BACKGROUND: Glioblastoma (GBM) was shown to relapse faster and displayed therapeutic resistance to antiangiogenic therapies (AATs) through an alternative tumor cell-driven mechanism of neovascularization called vascular mimicry (VM). We identified highly upregulated interleukin 8 (IL-8)-CXCR2 axis in tumor cells in high-grade human glioma and AAT-treated orthotopic GBM tumors. METHODS: Human GBM tissue sections and tissue array were used to ascertain the clin. relevance of CXCR2-pos. tumor cells in the formation of VM. We utilized U251 and U87 human tumor cells to understand VM in an orthotopic GBM model and AAT-mediated enhancement in VM was modeled using vatalanib (anti-VEGFR2) and avastin (anti-VEGF). Later, VM was inhibited by SB225002 (CXCR2 inhibitor) in a preclin. study. RESULTS: Overexpression of IL8 and CXCR2 in human datasets and histol. anal. was identified as a bonafide candidate to validate VM through in vitro and animal model studies. AAT-treated tumors displayed a higher number of CXCR2-pos. GBM-stem cells with endothelial-like phenotypes. Stable knockdown of CXCR2 expression in tumor cells led to decreased tumor growth as well as incomplete VM structures in the animal models. Similar data were obtained following SB225002 treatment. CONCLUSIONS: The present study suggests that tumor cell autonomous IL-8-CXCR2 pathway is instrumental in AAT-mediated resistance and VM formation in GBM. Therefore, CXCR2 can be targeted through SB225002 and can be combined with standard therapies to improve the therapeutic outcomes in clin. trials. 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.Like many other isomeric benzodiazines, phthalazine derivatives reveal numerous pharmacological and biological activities such as analgesic, anticonvulsant, antitumor, antiproliferative. 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

Vatalanib decrease the positive interaction of VEGF receptor-2 and P2X_2/3 receptor in chronic constriction injury rats was written by Liu, Shuangmei;Xu, Changshui;Li, Guilin;Liu, Han;Xie, Jinyan;Tu, Guihua;Peng, Haiying;Qiu, Shuyi;Liang, Shangdong. And the article was included in Neurochemistry International in 2012.Computed Properties of C20H15ClN4 This article mentions the following:

Neuropathic pain can arise from a lesion affecting the peripheral nervous system. Selective P2X₃ and P2X_2/3 receptors’ antagonists effectively reduce neuropathic pain. VEGF inhibitors are effective for pain relief. The present study investigated the effects of Vatalanib (VEGF receptor-2 (VEGFR-2) inhibitor) on the neuropathic pain to address the interaction of VEGFR-2 and P2X_2/3 receptor in dorsal root ganglia of chronic constriction injury (CCI) rats. Neuropathic pain symptoms following CCI are similar to most peripheral lesions as assessed by the Neuropathic Pain Symptom Inventory. Sprague-Dawley rats were randomly divided into sham group, CCI group and CCI rats treated with Vatalanib group. Mech. withdrawal threshold and thermal withdrawal latency were measured. Co-expression of VEGFR-2 and P2X₂ or P2X₃ in L4-6 dorsal root ganglia (DRG) was detected by double-label immunofluorescence. The modulation effect of VEGF on P2X_2/3 receptor agonist-activated currents in freshly isolated DRG neurons of rats both of sham and CCI rats was recorded by whole-cell patch-clamp technique. The mech. withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in CCI group were lower than those in sham group (p < 0.05). MWT and TWL in CCI rats treated with Vatalanib group were increased compared with those in CCI group (p < 0.05). VEGFR-2 and P2X₂ or P2X₃ receptors were co-expressed in the cytoplasm and surface membranes of DRG. The co-expression of VEGFR-2 and P2X₂ or P2X₃ receptor in CCI group exhibited more intense staining than those in sham group and CCI rats treated with Vatalanib group, resp. VEGF enhanced the amplitude of ATP and α,β-meATP -activated currents of both sham and CCI rats. Increment effects of VEGF on ATP and α,β-meATP -activated currents in CCI rats were higher than those in sham rats. Both ATP (100 μM) and α,β-meATP (10 μM)- activated currents enhanced by VEGF (1 nM) were significantly blocked by Vatalanib (1 μM, an inhibitor of VEGF receptors). The stain values of VEGFR-2, P2X₂ and P2X₃ protein expression in L4/5 DRG of CCI treated with Vatalanib group were significantly decreased compared with those in CCI group (p < 0.01). Vatalanib can alleviate chronic neuropathic pain by decreasing the activation of VEGF on VEGFR-2 and the pos. interaction between the up-regulated VEGFR-2 and P2X_2/3 receptors in the neuropathic pain signaling. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3Computed Properties of 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. Also, Phthalazinesare crucial precursors in the synthesis of many compounds with interesting pharmacological properties like phosphodiesterase inhibitors and blood platelet aggregation inhibitors.Computed Properties of C20H15ClN4

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

Synthesis and anti-tumor activity of 1-(4-chloroaniline)-4-(4-pyridylmethyl)-2,3-benzodiazine succinate was written by Chen, Guanhong;Wang, Jianing;Kong, Xue;Liu, Kechun. And the article was included in Yingyong Huaxue in 2011.Safety of N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine This article mentions the following:

1-(4-Chloroaniline)-4-(4-pyridylmethyl)-2,3-benzodiazine succinate I was synthesized by addition, rearrangement, substitution and halogenesis steps with phthalide and 4-pyridinecarbaldehydes as starting reagents. The intermediate and target compound I were characterized by ¹H NMR, MS and HPLC. After purification by recrystallization, the compound I (98.1% purity estimated by HPLC) was exptl. used to treat colorectal cancer nude mice. The result shows that this compound obviously restrains the growth of tumors. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3Safety 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. Phthalazine is isomeric with other naphthyridines including quinoxaline, cinnoline and quinazoline. Phthalazines are popular pharmacophores as they are the core chemical motifs in many commercially available drugs such as Azelastin (antihistamine), Vatalanib (vascular endothelial growth factor receptor (VEGFR) inhibitor), and Hydralazine (antihypertensive agent).Safety of N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem