Month: February 2023

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

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

Connection between taste and constitution of carboxylic hydrazides and their derivatives was written by Blanksma, J. J.;Bakels, H. A.. And the article was included in Recueil des Travaux Chimiques des Pays-Bas et de la Belgique in 1939.HPLC of Formula: 18393-54-9 This article mentions the following:

The presence of one CONHNH₂ group is insufficient to produce a sweet taste; at least 2 such groups are required and the result is not always a sweet taste, contrary to the conclusion of de Graaf (C. A. 32, 3340.6). The rule of Cohn (Die organische Gesckmackstoffe, Berlin, 1914, p. 731 (C. A. 8, 3605) that the NC group produces a bitter taste is confirmed. Condensation of CH₂(CONHNH₂)₂ (I), (CH₂CONHNH₂)₂ (II), CH₂(CONHNH₂)C(OH) (CONHNH₂)CH₂CONHNH₂ (III), 2-HOCH₂C₆H₄-CONHNH₂ (IV) and 5,2-O₂N(HOCH₂)C₆H₃CONHNH₂ (V) with the following aldehydes and ketones gave compounds with the m. ps. which follow, resp.: AcH, with I, 188°, with II, 250°; EtCHO, I, 175°, II, 238°; PrCHO, I, 169°, II, 241°; iso-PrCHO, I, 173°, II, 203°; BuCHO, I, 166° II, 221°; Me(CH₂)₅CHO, I, 157°; BzH, I, 236°, II, 252°, III, 213°, IV, 152°, V, 196°; 4-MeC₆H₄CHO, I, 222°, II, 235°, III, 200°; piperonal, I, 221°, II, 268°, III, 195° IV, 183°, V, 203°; vanillin, I, 219°, II, 209°; HOC₆H₄CHO, I, 255°, II, 285° III, 211°; 4-isomer, I, 202°, II, 240°, III, 280°; 2-O₂NC₆H₄CHO, I, 249°, II, 286°, III, 206° IV, 186°, V, 207°; 3-isomer, I, 228°, II, 315°, III, 185° IV, 186°, V, 189°; 4-isomer, I, 256°, II, 292° III, 274°, IV, 213°, V, 217°; 2-ClC₆H₄CHO, I, 229°, II, 269°, IV, 182°, V, 207°; 3-isomer, I, 210°, II, 254°, IV, 153°, V, 198°; 4-isomer, I, 257°, II, 288°, IV, 175°, V, 202°; PhCH₂CHO, I, 170°, II, 228°; 2-furaldehyde, I, 243°, II, 267°, III, 179°, IV, 168°, V, 181°; 5-Me derivative, I, 207°, II, 235°, III, 178°, IV, 183°, V, 161°; 5-HOCH₂ derivative, I, 187°, II, 199° III, 166°, IV, 157°, V, 166°; Me₂CO, I, 185°, II, 200°, IV, 147°, V, 185°; AcEt, I, 142°, II, 165°; Et₂CO, I, 130°, II, 160°; Pr₂CO, I, 109°, II, 173°; BzMe, I, 220°, II, 274°, III, 182°. In addition II gave the following condensation product with AcPr, m. 144°. None of the products from III have taste, and from I and II only the products with AcH, Me₂CO, AcEt and Et₂CO have any taste, bitter in all cases, although I, II and III are sweet. o-C₆H₄(CONHNHAc)₂ (VI) (Davidis, J. prakt. Chem. [2], 54, 66(1896)) has no taste, nor does o-C₆H₄(CONHAc) CONHNH₂, m. 174°, prepared by pouring hot VI with Ac₂O into cold H₂O. No taste was found for m-C₆H₄(CONHNH₂)₂ (VII), m. 227°, or p-C₆H₄(CONHNH₂)2 (VIII), m. 320°. From VII and VIII, resp., the Me₂CO derivatives, m. 255° and 310°, were slightly bitter, the BzH derivatives m. 254° and 336°, were tasteless. From VII, a tasteless BzMe derivative, m. 251°, was secured. From VIII the N-Me derivative, m. 239°, and the N,N’-di-Me derivative, m. 175°, were slightly bitter while the Ac derivative, m. 140°, was tasteless. The condensation product of IV with 5-(hydroxymethyl)-2-furaldehyde gave a bitter Ac derivative, m. 143°. The products from V are the most bitter of the whole series. From 5,2-H₂N(HOCH₂)C₆H₃CONHNH₂ with Me₂CO and BzH, tasteless products were secured, m. 179° and 177°, resp. A number of the above compounds which are tasteless have a faint bitter after-taste. The reaction of meconin and various of its substitution products with NH₂NH₂ and condensation of these products with Me₂CO and BzH were reinvestigated (Kleemann, Ber. 20, 875(1887); Anderson, Ann. 98, 47(1856); Tasman, C. A. 21, 3357). These substances were either bitter or tasteless. The following generalizations regarding constitution and taste may be drawn from this work: the condensation products of hydrazides with aldehydes and ketones are bitter when soluble enough to taste; 2 or more CONHNH₂ groups located near to each other are required to produce a sweet taste; the introduction of a Ph group favors a bitter taste. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9HPLC of Formula: 18393-54-9).

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. Both pyridazine and phthalazine give rise to very good TREPR signals in rigid media at low temperatures.HPLC of Formula: 18393-54-9

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

Central nervous system active compounds. XI. 1-(3-Phthalidyl)phthalazin-4-ones was written by Prager, Rolf;Ward, A. David;Marshall, Philip;Mooney, Brett. And the article was included in Heterocycles in 1982.Formula: C9H8N2O2 This article mentions the following:

Phthalidylphthalazinones I (R = H, Me, Et; R¹, R⁶ = H; R¹R², R⁵R⁶ = OCH₂O; R² = H, OMe, Me, NO₂; R³ = H, Me, OMe; R⁴, R⁵ = H, OMe, Cl) can be readily prepared by the reaction of hydrazines with the corresponding biphthalide. The reaction with unsym. biphthalides appears to be controlled mainly by electronic factors. Phthalidylphthalazinone undergoes the Mannich reaction leading to a 3-substituted product. 1-Chlorophthalazine reacts with BuLi by addition at C-4; the resulting anion is alkylated at C-3 with 2-HCOC₆H₄CO₂Me. The compounds cause loss of muscular control in mice, but their insolubility hinders further pharmacol. investigation. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3-dihydrophthalazine-1,4-dione (cas: 18393-54-9Formula: C9H8N2O2).

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. 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).Formula: C9H8N2O2

Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem

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