Tag: 600-700

Repurposed FDA-Approved drug sorafenib reduces replication of Venezuelan equine encephalitis virus and other alphaviruses was written by Lundberg, Lindsay;Brahms, Ashwini;Hooper, Idris;Carey, Brian;Lin, Shih-Chao;Dahal, Bibha;Narayanan, Aarthi;Kehn-Hall, Kylene. And the article was included in Antiviral Research in 2018.Recommanded Product: 145040-37-5 This article mentions the following:

The New World alphaviruses -Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV resp.) – cause a febrile disease that is often lethal in equines and children and leads to long-term neurol. sequelae in survivors. Endemic to the Americas, epizootic outbreaks of the three viruses occur sporadically in the continental United States. All three viruses aerosolize readily, replicate to high titers in cell culture, and have low infectious doses. Addnl., there are no FDA-approved vaccines or therapeutics for human use. To address the therapeutic gap, a high throughput assay utilizing a luciferase reporter virus, TC83-luc, was performed to screen a library of com. available, FDA-approved drugs for antiviral activity. From a group of twenty compounds found to significantly decrease luminescence, the carcinoma therapeutic sorafenib inhibited replication of VEEV-TC83 and TrD in vitro. Addnl., sorafenib inhibited replication of EEEV and two Old World alphaviruses, Sindbis virus and chikungunya virus, at 8 and 16h post-infection. Sorafenib caused no toxicity in Vero cells, and coupled with a low EC₅₀ value, yielded a selectivity index of >19. Mechanism of actions studies suggest that sorafenib inhibited viral translation through dephosphorylation of several key proteins, including eIF4E and p70S6K, leading to a reduction in viral protein production and overall viral replication. In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5Recommanded Product: 145040-37-5).

1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) belongs to imidazole derivatives. Imidazole is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole is incorporated into many important biological compounds. The most pervasive is the amino acid histidine, which has an imidazole side-chain. Histidine is present in many proteins and enzymes, e.g. by binding metal cofactors, as seen in hemoglobin.Recommanded Product: 145040-37-5

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Applying different techniques to improve the bioavailability of candesartan cilexetil antihypertensive drug was written by Aly, Usama Farghaly;Sarhan, Hatem Abdel-Monsef;Ali, Taha F. S.;Abd El-Bakey Sharkawy, Hosny. And the article was included in Drug Design, Development and Therapy in 2020.HPLC of Formula: 145040-37-5 This article mentions the following:

Purpose: The objective of this study was to compare different techniques to enhance the solubility and dissolution rate, and hence the bioavailability of candesartan cilexetil. Methods: To achieve this target, various techniques were employed such as solid dispersions, inclusion complexes, and preparation of candesartan nanoparticles. Following the preparations, all samples were characterized for their physicochem. properties, and the samples of the best results were subjected to further bioavailability studies. Results: Results of dissolution studies revealed an increase in the dissolution rate of all samples. The highest dissolution rate was achieved using solid dispersion of the drug with PVP K-90 (1:4). Physicochem. investigations (XR, DSC, and FT-IR) suggested formation of hydrogen bonding and changing in the crystalline structure of the drug. Regarding the inclusion complexes, more stable complex was formed between HP-β-CD and CC compared to β-CD, as indicated by phase solubility diagrams. Antisolvent method resulted in the preparation of stable nanoparticles, as indicated by ζ potential, with average particle size of 238.9 ± 19.25 nm using PVP K-90 as a hydrophilic polymer. The best sample that gave the highest dissolution rate (CC/PVP K-90 1:4) was allowed for further pharmacokinetic studies using UPLC MS/MS assay of rabbit plasma. Results showed a significant increase in the bioavailability of CC from ~15% to ~48%. Conclusion: The bioavailability of CC was significantly improved from ~15% to ~48% when formulated as SDs with PVP K-90 with 1:4 drug:polymer ratio. In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5HPLC of Formula: 145040-37-5).

1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) belongs to imidazole derivatives. Imidazole is a heterocyclic compound with a five-membered planar ring. It is amphoteric and highly polar. Imidazole also acts as a microtubule destabilizing agents and inhibits topoisomerase and Cytochrome P450 Family 26 Subfamily A Member 1 (CYP26A1) enzymes.HPLC of Formula: 145040-37-5

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Self nano-emulsifying drug delivery system to enhance solubility and dissolution of candesartan cilexetil was written by Raghuveer, Pathuri;Rani, Avula Prameela. And the article was included in International Journal of Pharmaceutical Investigation in 2020.Synthetic Route of C33H34N6O6 This article mentions the following:

Self nano-emulsifying drug delivery system (SNEDDS) of candesartan cilexetil was explored to enhance its oral bioavailability. SNEDDS has tremendous potential in enhancing oral bioavailability of poorly aqueous soluble therapeutic agents. SNEDDS are pre-concentrate mixture of oil, surfactant and co-surfactant produces nanoemulsion after oral administration due to mild agitation produced by gastro motility within the size range of 20-200nm. The formulations were developed by selecting capmul MCM, triacetin and caprylic acid under the oil phase based on solubility of drug; cremophore RH40, brij35 under surfactants category and transcutol P under co-surfactant on basis of their emulsification property. Optimum concentrations were choosen from the Terinary phase diagrams and evaluated for their properties. From the results of ternary diagrams 16 formulations were selected (A1, A2, A3, A4, B1, B2, C1, C2, C3, C4, D1, D2, E1, E2, F1, F2) and subjected to characterization studies. Best formulations were subjected to particle size anal. and in vitro release studies. Among selected formulations, A1 and C1 have shown high in vitro drug release profiles with less self-emulsification time having grade A dispersibility without any precipitation and phase separation Concentration of surfactant helps in reducing the size of the particle when compared to the co-surfactant concentration Enhanced dissolution of candesartan cilexitil may be attributed to the spontaneous formation of nanoemulsion in vitro with a decreased particle size that leads to the increased surface area leaving the drug candesartan as finely dispersed particles in dissolution media. Formulation C1 consists of triacetin oil 30% weight/weight, cremophore RH 40 6%weight/weight and transcutol P 64%weight/weight showed best emulsification characteristics like 99% percent transmittance, with increased dissolution profile (98%) than pure drug (45%) with nano range goblet size (165.9nm). In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5Synthetic Route of C33H34N6O6).

1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) belongs to imidazole derivatives. Imidazole is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. This ring system is present in important biological building blocks, such as histidine and the related hormone histamine.Synthetic Route of C33H34N6O6

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Comparative Pharmaceutical Evaluation of Candesartan and Candesartan Cilexetil: Physicochemical Properties, In Vitro Dissolution and Ex Vivo In Vivo Studies was written by Amer, Ahmed M.;Allam, Ahmed N.;Abdallah, Ossama Y.. And the article was included in AAPS PharmSciTech in 2018.Computed Properties of C33H34N6O6 This article mentions the following:

The aim of the present work is to answer the question is it possible to replace the ester prodrug candesartan cilexetil (CC) by its active metabolite candesartan (C) to bypass the in vivo variable effect of esterase enzymes. A comparative physicochem. evaluation was conducted through solubility, dissolution, and stability studies; addnl., ex vivo permeation and in vivo studies were assessed. C demonstrated higher solubility over CC at alk. pH. Moreover, dissolution testing using the pharmacopeial method showed better release profile of C even in the absence of surfactant in the testing medium. Both drugs demonstrated a slight degradation in acidic pH after short-term stability. Instead, shifting to alk. pH of 6.5 and 7.4 showed superiority of C solution stability compared to CC solution The ex vivo permeation results demonstrated that the parent compound C has a significant (P < 0.05) enhanced permeation compared to its prodrug from CC, that agreed with in vivo results in which C suspension reached significantly (P < 0.05) higher Cmax of 1.39 ± 0.59μg/mL at Tmax of 0.66 ± 0.11 h, while CC suspension reached Cmax of 0.47 ± 0.22μg/mL at Tmax of 2.00 ± 0.27 h, a lag period of 40 min is needed prior to detection of any absorbed CC in plasma. Those findings are not in agreement with the previously reported rationale on the prodrug formation owing to the poor permeability of the parent compound, suggesting the possibility of marketing the parent drug candesartan for clin. use similarly to azilsartan and its prodrug. In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5Computed Properties of C33H34N6O6).

1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) belongs to imidazole derivatives. Imidazole derivatives generally have good solubility in protic solvents. Simple imidazole derivatives, such as 1H-imidazole, 2-methyl-1H-imidazole, and 1,2-dimethylimidazole, have very high solubility in water. Imidazole has been usedin the lysis, wash and elution buffer for the purification of histidine tagged Sonic Hedgehog(shh-N) protein, in elution buffer in stepwise gradient for the purification of histidine tagged aldo keto reductases using nickel affinity chromatography, as a component of homogenization buffer for the purification of phagosomal compartments from dendritic cells.Computed Properties of C33H34N6O6

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Development of a high-throughput NanoBRET screening platform to identify modulators of the RAS/RAF interaction was written by Durrant, David E.;Smith, Emily A.;Goncharova, Ekaterina I.;Sharma, Nirmala;Alexander, Patrick A.;Stephen, Andrew G.;Henrich, Curtis J.;Morrison, Deborah K.. And the article was included in Molecular Cancer Therapeutics in 2021.Formula: C33H34N6O6 This article mentions the following:

Activating mutations in RAS are found in approx. 30% of human cancers, resulting in the delivery of a persistent signal to critical downstream effectors that drive tumorigenesis. RAS-driven malignancies respond poorly to conventional cancer treatments and inhibitors that target RAS directly are limited; therefore, the identification of new strategies and/or drugs to disrupt RAS signaling in tumor cells remains a pressing therapeutic need. Taking advantage of the live-cell bioluminescence resonance energy transfer (BRET) methodol., we describe the development of a NanoBRET screening platform to identify compounds that modulate binding between activated KRAS and the CRAF kinase, an essential effector of RAS that initiates ERK cascade signaling. Using this strategy, libraries containing synthetic compounds, targeted inhibitors, purified natural products, and natural product extracts were evaluated. These efforts resulted in the identification of compounds that inhibit RAS/RAF binding and in turn suppress RAS-driven ERK activation, but also compounds that have the deleterious effect of enhancing the interaction to upregulate pathway signaling. Among the inhibitor hits identified, the majority were compounds derived from natural products, including ones reported to alter KRAS nanoclustering (ophiobolin A), to impact RAF function (HSP90 inhibitors and ROS inducers) as well as some with unknown targets and activities. These findings demonstrate the potential for this screening platform in natural product drug discovery and in the development of new therapeutic agents to target dysregulated RAS signaling in human disease states such as cancer. In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5Formula: C33H34N6O6).

1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam.Formula: C33H34N6O6

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Optimization of component variables for self micro emulsifying drug delivery systems by using extreme vertices mixture designs was written by Mittal, Pooja;Seth, Nimrata;Kapoor, Ramit;Mishra, Brahmeshwar. And the article was included in International Research Journal of Pharmacy in 2018.Product Details of 145040-37-5 This article mentions the following:

Self-micro emulsifying drug delivery systems (SMEDDS) are the isotropic mixtures of natural or synthetic oils, solid or liquid surfactants, and hydrophilic co-solvents/surfactants that have a unique ability of forming fine oil-in-water (o/w) micro emulsions upon mild agitation followed by dilution in aqueous media, such as GI fluids. These were developed to overcome problems like low solubility and oral bioavailability associated with the delivery of Candesartan Cilexetil (CSC), a poorly water-soluble Angiotensin receptor blocker. Solubility of CSC in oily phases and surfactants was determined to identify components of SMEDDS. The composition of optimized formulation was Carbitol (50%), Cremophore EL (20%), Propylene Glycol (30%) and CSC (40 mg) as oil, surfactant, Co surfactant and drug, resp. Extreme Vertices Mixture design was employed to optimize the formulations and the final formulation was optimized by utilizing desirability function approach. The globule size of optimized formulation was found to be approx. 47 nm which was not affected by the pH of dilution medium. The optimized SMEDDS released CSC approx. 90% irresp. of the pH of dissolution medium. The present study ratified the use of principles of quality by design in optimization of pharmaceutical formulations. In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5Product Details of 145040-37-5).

1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) belongs to imidazole derivatives. Imidazole is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. This ring system is present in important biological building blocks, such as histidine and the related hormone histamine.Product Details of 145040-37-5

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Pharmacogenetic aspects of the interaction of AT1 receptor antagonists with ATP-binding cassette transporter ABCG2 was written by Ripperger, Anne;Krischer, Anna;Robaa, Dina;Sippl, Wolfgang;Benndorf, Ralf A.. And the article was included in Frontiers in Pharmacology in 2018.Quality Control of 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate This article mentions the following:

The ATP-binding cassette transporter ABCG2 (BCRP and MXR) is involved in the absorption, distribution, and elimination of numerous drugs. In addition, genetic variability within the ABCG2 gene may influence the ability of the transporter to interact with ARBs. Thus, the aim of this study was to characterize the ARB-ABCG2 interaction in the light of naturally occurring variations (F489L, R482G) or amino acid substitutions with in silico-predicted relevance for the ARB-ABCG2 interaction (Y469A; M483F; Y570A). For this purpose, ABCG2 variants were expressed in HEK293 cells and the impact of ARBs on ABCG2 activity was studied in vitro using the pheophorbide A (PhA) efflux assay. First, we demonstrated that both the F489L and the Y469A substitution, resp., reduced ABCG2 protein levels in these cells. Moreover, both substitutions enhanced the inhibitory effect of candesartan cilexetil, irbesartan, losartan, and telmisartan on ABCG2-mediated PhA efflux, whereas the R482G substitution blunted the inhibitory effect of candesartan cilexetil and telmisartan in this regard. In conclusion, our data indicate that the third transmembrane helix and adjacent regions of ABCG2 may be of major importance for the interaction of ARBs with the ABC transporter. Moreover, we conclude from our data that individuals carrying the F489L polymorphism may be at increased risk of developing ABCG2-related drug-drug interactions in multi-drug regimens involving ARBs. In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5Quality Control of 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate).

1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) belongs to imidazole derivatives. The solubility of imidazoles in ethers is lower than that in alcohols and decreases with increasing chain length of the ethers . In contrast, the solubility of benzimidazoles in alcohols (C3–C6) is higher than in water and generally decreases with a Imidazole has been usedin the lysis, wash and elution buffer for the purification of histidine tagged Sonic Hedgehog(shh-N) protein, in elution buffer in stepwise gradient for the purification of histidine tagged aldo keto reductases using nickel affinity chromatography, as a component of homogenization buffer for the purification of phagosomal compartments from dendritic cells.Quality Control of 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem