Heterocyclic Building Blocks-phthalazine

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

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

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

Development and application of catalytic tyrosine modification was written by Sato, Shinichi;Tsushima, Michihiko;Nakamura, Kosuke;Nakamura, Hiroyuki. And the article was included in Yakugaku Zasshi in 2018.Recommanded Product: 18393-54-9 This article mentions the following:

The chem. labeling of proteins with synthetic probes is a key technique used in chem. biol., protein-based therapy, and material science. Much of the chem. labeling of native proteins, however, depends on the labeling of lysine and cysteine residues. While those methods have significantly contributed to native protein labeling, alternative methods that can modify different amino acid residues are still required. Herein we report the development of a novel methodol. of tyrosine labeling, inspired by the luminol chemiluminescence reaction. Tyrosine residues are often exposed on a protein surface and are thus expected to be good targets for protein functionalization. In our studies so far, we have found that (1) hemin oxidatively activates luminol derivatives as a catalyst, (2) N-Me luminol derivative specifically forms a covalent bond with a tyrosine residue among the 20 kinds of natural amino acid residues, and (3) the efficiency of tyrosine labeling with N-Me luminol derivative is markedly improved by using horseradish peroxidase (HRP) as a catalyst. We were able to use mol. oxygen as an oxidant under HRP/NADH conditions. By using these methods, the functionalization of purified proteins was carried out. Because N-Me luminol derivative is an excellent protein labeling reagent that responds to the activation of peroxidase, this new method is expected to open doors to such biol. applications as the signal amplification of HRP-conjugated antibodies and the detection of protein association in combination with peroxidase-tag technol. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9Recommanded Product: 18393-54-9).

2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9) 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 pyridazines, phthalazines, the other benzopyridazines, were also prepared most frequently through the condensation of hydrazines with carbonyl-containing compounds, typically phthalate derivatives. Recommanded Product: 18393-54-9

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

Hydrazinolysis study of phthalimido- and phthalisoimido-penicillin amide derivatives was written by Ceric, Helena;Sindler-Kulyk, Marija. And the article was included in ARKIVOC (Gainesville, FL, United States) in 2009.Electric Literature of C9H8N2O2 This article mentions the following:

New phthalimido-penicillin amide (6-PhtPABn, I) and phthalisoimido-penicillin amide (6-isoPhtPABn, II) were prepared and the susceptibility of their different carbonyl functions toward hydrazine derivatives investigated in order to establish the feasibility of dephthaloylation within penicillin class compounds Hydrazinolysis of I resulted in dephthaloylation and β-lactam ring opening into thiazolidine derivatives, while in the case of II, the desired amino-penicillin amide was isolated in low yield. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9Electric Literature of C9H8N2O2).

2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9) 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.Electric Literature of C9H8N2O2

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

Design, synthesis and antitumor activity of phthalazine-1,4-dione-based menaquinone analogs was written by Fujii, Shinya;Miura, Takahiro;Oikawa, Tsuyoshi;Qin, Xian-Yang;Kojima, Soichi;Kagechika, Hiroyuki. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2021.Related Products of 18393-54-9 This article mentions the following:

New chemotherapeutics are needed to treat hepatocellular carcinoma (HCC), and menaquinones, homologs of vitamin K consisting of a 1,4-naphthoquinone core and a (poly)isoprene chain, are potential candidates. In this study, we designed and synthesized a series of phthalazine-1,4-dione-based menaquinone analogs such as I. Among them, compounds bearing the intact isoprene chain exhibited selective antiproliferative activity towards HCC cell line JHH7, as compared with normal hepatocytes. The geranyl derivative I showed submicromolar potency, and might be a promising lead compound for anticancer agents. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9Related Products of 18393-54-9).

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 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 18393-54-9

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

Novel rearrangement of a diaziridine was written by Heine, Harold W.;Lehman, Laura S.;Glaze, Alan P.;Douglas, Alan W.. And the article was included in Journal of Organic Chemistry in 1980.Quality Control of 2-Methyl-2,3-dihydrophthalazine-1,4-dione This article mentions the following:

Diaziridine I isomerizes in refluxing toluene or in Me₂SO solutions containing KOCMe₃ into the phthalazinone II. The structure of II was characterized by ¹³C and ¹H NMR and by alk. hydrolysis and N-methylation. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9Quality Control of 2-Methyl-2,3-dihydrophthalazine-1,4-dione).

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 anticonvulsant, antitumor, antiproliferative, antiepileptic, anti-inflammatory, and vasorelaxant. As with cinnolines, phthalazines were also prepared most frequently through condensations of hydrazine derivatives and carbonyl-containing compounds.Quality Control of 2-Methyl-2,3-dihydrophthalazine-1,4-dione

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

Reaction of DMSO with phthalazinediones was written by Czuba, Wladyslaw;Sedzik-Hibner, Dorota. And the article was included in Universitatis Iagellonicae Acta Chimica in 1991.Name: 2-Methyl-2,3-dihydrophthalazine-1,4-dione This article mentions the following:

Treatment of 1,4-phthalazinedione with DMSO afforded 2-(methylthiomethyl)phthalazine-1,4-dione, 2,3-bis(methylthiomethyl)phthalazine-1,4-dione, and 4-(methylthiomethoxy)-2-(methylthiomethyl)phthalazin-1-one in a 8:3:3 ratio. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9Name: 2-Methyl-2,3-dihydrophthalazine-1,4-dione).

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. As with cinnolines, phthalazines were also prepared most frequently through condensations of hydrazine derivatives and carbonyl-containing compounds.Name: 2-Methyl-2,3-dihydrophthalazine-1,4-dione

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem