Tag: 600-700

Novel Computational Approach by Combining Machine Learning with Molecular Thermodynamics for Predicting Drug Solubility in Solvents was written by Ge, Kai;Ji, Yuanhui. And the article was included in Industrial & Engineering Chemistry Research in 2021.SDS of cas: 145040-37-5 This article mentions the following:

In this work, a novel strategy that combined mol. thermodn. and machine learning was proposed to accurately predict the solubility of drugs in various solvents. The strategy was based on 16 mol. descriptors representing drug-drug interactions and drug-solvent interactions including phys. parameters, pure perturbed-chain statistical associating fluid theory (PC-SAFT) parameters of drugs and solvents, and mixing rules. These mol. descriptors were inputted into five machine learning algorithms [multiple linear regression (MLR), artificial neural network (ANN), random forest (RF), extremely randomized trees (ET), and support vector machine (SVM)] to train the predictive model. A single-hidden-layer neural network was finally determined as the predictive model for predicting the solubility of drugs in various solvents. The drug solubility in the generalization evaluation set has also been successfully predicted, which indicates the good prediction performance of the model. Three directions for improving the model were summarized as adding mol. descriptors of drug-solvent interactions in the water system and drug-drug interactions in the organic solvent system and expanding the dataset to adequately obtain the features of multiple drugs. These findings show that the proposed model has the capability of solubility prediction, which is expected to provide important information for drug development and drug solvent screening. 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: 145040-37-5SDS of cas: 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. Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam.SDS of cas: 145040-37-5

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Formulation and evaluation of candesartan co-precipitate with hydrophilic polymers; preparation of orodispersible tablets was written by Deweda, Asmaa M.;Essa, Ebtessam A.;Donia, Ahmed A.. And the article was included in European Journal of Biomedical and Pharmaceutical Sciences in 2019.Application of 145040-37-5 This article mentions the following:

Candesartan cilexetil is an angiotensin-receptor blocker that suffer from inadequit and variable oral bioavailability due to its poor aqueous solubility and presystemic metabolism Therefore, the objectives of this study was to enhance candesartan cilexetil dissolution with subsequent preparation of mouth dispersable tablets. The drug was precipitated from its ethanolic solution over Aerosil 200 as carrier for the deposited microcrystals. To improve surface wettability, the precipitation step was performed in presence of hydrophilic polymer. The selected polymers were polyvinylpyrrolidone 40T (PVP), hydroxypropylmethyl cellulose E5 (HPMC), Poloxamer 407 and polyethylene glycol6000 (PEG). The products were evaluated regarding dissolution pattern. Phys. characterization was also evaluated for selected formulations. Thermal behavior and X-ray powder diffraction results confirmed reduced drug crystalinity. Infra-red spectroscopy indicated drug-excipient compatibilty. All formulations showed imrovement in drug dissolution compared to pure drug. Presence of polymer resulted in higher initial release and dissolution efficiency. Best formulations regarding dissolution were successifly used in the preparation of oral dispersible tablets with fast drug release. Drug precipitation over carrier with large surface area in presence of hydrophilic polymer is a promising approach for enhancing dissolution rate of poorly soluble drugs. 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: 145040-37-5Application 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. Imidazole based anticancer drug find applications in cancer chemotherapy. It is used as buffer component for purification of the histidine tagged recombinant proteins in immobilized metal-affinity chromatography (IMAC).Application of 145040-37-5

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Sustainable spectrophotometric determination of antihypertensive medicines reducing COVID-19 risk via paired wavelength data processing technique – Assessment of purity, greenness and whiteness was written by El-Hanboushy, Sara;Marzouk, Hoda M.;Fayez, Yasmin M.;Abdelkawy, Mohamed;Lotfy, Hayam M.. And the article was included in Sustainable Chemistry and Pharmacy in 2022.Recommanded Product: 145040-37-5 This article mentions the following:

Recent studies have reported that using certain antihypertensive therapies such as angiotensin II receptor blockers (ARBs) is associated with mitigation of fatal outcomes and enhancing clin. features of patients having hypertension during coronavirus pandemic. Thus, in the current work an innovative, effective, white and sustainable spectrophotometric technique called paired wavelength data processing technique (PWDPT) was developed for evaluation of recommended antihypertensive combination therapies incorporating candesartan cilexetil (CAN) and hydrochlorothiazide (HCT). This technique included three methods, namely, absorbance resolution (AR), amplitude resolution (PR) and ratio extraction (RE). Linearity ranges were (5.0 μg/mL – 50.0 μg/mL) and (2.0 μg/mL – 24.0 μg/mL) for CAN and HCT, resp. Validation and confirmation of all suggested methods were conducted in accordance with ICH guidelines, producing satisfactory results within the accepted limits. Statistical comparison was achieved between the attained results from suggested methods and those attained from official methods, in which insignificant difference was existed. The suggested methods were successfully employed for identification of the studied drugs as well as determination of their spectral recognition and evaluation of the purity in their combined formulations. The proposed methods followed the principles of green anal. chem., where their greenness was evaluated and compared with the official potentiometric and HPLC methods via using four tools, namely, National Environmental Methods Index (NEMI), the Anal. Eco-Scale, the Green Anal. Procedure Index (GAPI) and Anal. greenness metric (AGREE) which affirmed the eco-friendly nature of the proposed methods. Moreover, studying the whiteness features was performed using the recently introduced RGB12 model. The acceptable results along with the sustainability, simplicity, affordability and low-cost of the proposed methods encourages their utilization in the quality control laboratories 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. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. This ring system is present in important biological building blocks, such as histidine and the related hormone histamine.Recommanded Product: 145040-37-5

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Formulation and development of candesartan cilexetil fast dissolving tablets by sublimation technique was written by Priya, Hunashal Sarah;Patil, Basawaraj S.;Jeevanagi, Ravindra S.. And the article was included in American Journal of PharmTech Research in 2019.Reference of 145040-37-5 This article mentions the following:

Candesartan cilexetil is a prodrug of candesartan – a compound that inhibits binding of angiotensin II to the AT1 – receptor. It is mainly used in the treatment of hypertension. In the present work attempts were mase to prepare fast dissolving tablets of candesartan cilexetil by sublimation technique. The prepared formulations were evaluated for pre-compressional and postcompressional parameters. The compatibility of drug with other ingredients was checked by FTIR studies, these results revealed that there was no interaction between dug and other excipients. The values of pre-compressional parameters were within prescribed limits and indicated good free flowing properties. In all the formulations the hardness test indicates good mech. strength. Friability of all formulations was less than 1. Drug content was found to be high (≥ 100.27%) and uniform in all the formulations. The tablet thickness was found to be 3.14 – 3.47. The weight variation results revealed that average percentage deviation was less then ± 7.5%, which provides good uniformity in all formulations. The disintegration time of the tablets decreased significantly with increase in the concentration of subliming agent. The formulations CSC3, CSM3, CSA3, and CSU3 50% of drug released in 1.38, 2.55, 4.00 and 3.57 min, and 90% of drug released in 3.39, 6.04, 7.50 and 7.18 min. The formulation CS (control) released 42.16% in 60 min. Stability study carried out as per ICH guidelines for three months and results revealed that upon storage disintegration time of tablets decreased significantly (p<0.05). The results concluded that by adopting a systemic formulation approach, an optimum point could be reached in the shortest time with min. efforts. Sublimation technique would be an effective alternative approach compared with the use of more expensive adjuvants in the formulations of fast dissolving tablets. 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: 145040-37-5Reference 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. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. 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.Reference of 145040-37-5

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Formulation and characterization of transdermal patch of Candesartan Celexitil was written by Shabnam, Hira;Singh, Dua Jagdeep;Prasad, D. N.;Anchal, Puri;Sahil, Kaushal. And the article was included in Journal of Drug Delivery and Therapeutics in 2019.Computed Properties of C33H34N6O6 This article mentions the following:

The aim of the present study is to formulate and characterized the transdermal patch of Candesartan celexitil. The objective is study was to increase the bioavailability of drug. In the present study, transdermal patch of Candesartan celexitil were prepared by solvent casting technique employing HPMC cps 50 polymer and glycerin as plasticizer using mercury as substrate. Total thirteen formulation (F1-F13) were prepared having drug and polymer ratio (1:2, 1:4, 1:6, 1:8, and 1:10). From the selected batch F2 containing drug polymer ratio (1:4), four formulations each were prepared and evaluated containg drug urea (1-4%) and oleic acid (1-4%) as permeation enhancer. The prepared transdermal patches were evaluated on the basis of different parameters like weigh, thickness, folding endurance, percent moisture absorption, percent moisture loss, drug content uniformity, in vitro skin permeation study. The fabricated final transdermal patches were further subjected to in vitro permeation study. In order to confirm the exact mechanism of drug release from all the patches, the data were computed and graphed according to Korsmeyer equation. Diffusion exponent of release process controlled by Super case II transport Non- Fickian diffusion, n values of Korsmeyer- Peppas model shows a combination of diffusion and dissolution mechanism indicating the drug release from the formulation was controlled by more than one process. It was concluded that the prepared formulation F13 (4% w/v of oleic acid) showed highest cumulative percent drug release and increase the bioavailability of the drug. 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. 1H-imidazole is an imidazole tautomer which has the migrating hydrogen at position 1. It is a conjugate base of an imidazolium cation. It is a conjugate acid of an imidazolide. It is a tautomer of a 4H-imidazole. Imidazole based anticancer drug find applications in cancer chemotherapy. It is used as buffer component for purification of the histidine tagged recombinant proteins in immobilized metal-affinity chromatography (IMAC).Computed Properties of C33H34N6O6

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Muco-adhesive buccal tablets of candesartan cilexetil for oral delivery: preparation, in-vitro and ex-vivo evaluation was written by Samanthula, Kumara Swamy;Bairi, Agaiah Goud;Mahendra, Kumar C. B.. And the article was included in Journal of Drug Delivery and Therapeutics in 2021.HPLC of Formula: 145040-37-5 This article mentions the following:

Candesartan cilexetil (CC) is an angiotensin II-receptor blocker (ARB). The antihypertensive effect of CC 4-16 mg/day was as great as that of other once-daily dosage regimens. Candesartan cilexetil has high first-pass metabolism and low oral bioavailability. The bioavailability of such drugs may be significantly improved if delivered through the buccal route; hence mucosal delivery is one of the alternative methods of systemic drug delivery. This study’s objective was to develop mucoadhesive buccal tablets of candesartan cilexetil using carbopol-934P, hydroxyl Pr Me cellulose (HPMC), Eudragit RLPO, and sodium carboxy Me cellulose (Na-CMC) as mucoadhesive polymers. Prepd CC buccal tablet formulations were evaluated for an optimized system based on physicochem. properties, ex-vivo residence time, in-vitro, and ex vivo permeation studies. The evaluation parameters of the tablets were within the acceptable Pharmacopoeial limits. However, the swelling and bio-adhesive time were increased with increasing polymer concentrations The in-vitro release research shown that buccal tablets with sodium carboxy Me cellulose (Na-CMC) exhibited a higher release than all other formulations and have been considered as optimized CC formulation. The release mechanism from kinetic methods suggests that the drug release follows zero-order kinetics with a diffusion mechanism. Further, in-vivo research in animal fashions is required to prove the bioavailability performance of the formulation. 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. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. 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.HPLC of Formula: 145040-37-5

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Preparation and In vitro characterization of a novel self-nano emulsifying drug delivery system for a fixed-dose combination of candesartan cilexetil and hydrochlorothiazide was written by Zewail, Moataz B.;El-Gizawy, Sanaa A.;Osman, Mohamed A.;Haggag, Yusuf A.. And the article was included in Journal of Drug Delivery Science and Technology in 2021.Electric Literature of C33H34N6O6 This article mentions the following:

A fixed-dose combination of Candesartan cilexetil (CAN) and Hydrochlorothiazide (HCTZ) is commonly used for the management of hypertension. CAN (BCS class II) and HCTZ (BCS class IV) suffer from inadequate oral bioavailability. Herein, the study aims to design a self-nano emulsifying drug delivery system (SNEDDS) containing a fixed-dose combination of both drugs to enhance their dissolution rate and hence oral bioavailability. Formulation of fixed-dose combination-loaded SNEDDS was carried out using various oils, surfactants, and co-surfactants, and phase diagrams were plotted using different ratios. In vitro characterizations of drug-loaded SNEDDS were achieved through optical clarity, emulsification efficiency, globule size, morphol., viscosity, drug-excipient interactions, and thermodn. stability. The in vitro release profiles of both drugs from optimized SNEDDS and their in vivo biol. activity compared to free drugs and a marketed product were studied. Optimized formulas showed a percentage transmittance greater than 90%, emulsification time less than 1 min, globule size in the nanometric range of (27-69 nm), and superior thermodn. stability after dilution and at different pH values. Fourier Transform Infra-Red (FTIR) studies demonstrated the absence of physicochem. interactions between drugs and additives. Transmission electron microscopy (TEM) images revealed spherical, non-aggregated globules that were consistent with the results of size anal. Optimized SNEDDS showed a better release profile for both drugs than those of pure drugs and marketed products and therefore, higher biol. activity was observed in hypertensive rats. SNEDDS can be used as a promising drug delivery carrier for improvement of the dissolution rate and the pharmacodynamic activity of the antihypertensive fixed-dose combination of CAN/HCTZ. 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: 145040-37-5Electric Literature 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. 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 based anticancer drug find applications in cancer chemotherapy. It is used as buffer component for purification of the histidine tagged recombinant proteins in immobilized metal-affinity chromatography (IMAC).Electric Literature of C33H34N6O6

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

A repurposed drug screen for compounds regulating aquaporin 5 stability in lung epithelial cells was written by Villandre, John;White, Virginia;Lear, Travis B.;Chen, Yanwen;Tuncer, Ferhan;Vaiz, Emily;Tuncer, Beyza;Lockwood, Karina;Camarco, Dan;Liu, Yuan;Chen, Bill B.;Evankovich, John. And the article was included in Frontiers in Pharmacology in 2022.Recommanded Product: 145040-37-5 This article mentions the following:

Aquaporin 5 (AQP5) is expressed in several cell types in the lung and regulates water transport, which contributes to barrier function during injury and the composition of glandular secretions. Reduced AQP5 expression is associated with barrier dysfunction during acute lung injury, and strategies to enhance its expression are associated with favorable phenotypes. Thus, pharmacol. enhancing AQP5 expression could be beneficial. Here, we optimized a high-throughput assay designed to detect AQP5 abundance using a cell line stably expressing bioluminescent-tagged AQP5. We then screened a library of 1153 compounds composed of FDA-approved drugs for their effects on AQP5 abundance. We show compounds Niclosamide, Panobinostat, and Candesartan Celexitil increased AQP5 abundance, and show that Niclosamide has favorable cellular toxicity profiles. We determine that AQP5 levels are regulated in part by ubiquitination and proteasomal degradation in lung epithelial cells, and mechanistically Niclosamide increases AQP5 levels by reducing AQP5 ubiquitination and proteasomal degradation Functionally, Niclosamide stabilized AQP5 levels in response to hypotonic stress, a stimulus known to reduce AQP5 levels. In complementary assays, Niclosamide increased endogenous AQP5 in both A549 cells and in primary, polarized human bronchial epithelial cells compared to control-treated cells. Further, we measured rapid cell volume changes in A549 cells in response to osmotic stress, an effect controlled by aquaporin channels. Niclosamide-treated A549 cell volume changes occurred more rapidly compared to control-treated cells, suggesting that increased Niclosamide-mediated increases in AQP5 expression affects functional water transport. Taken together, we describe a strategy to identify repurposed compounds for their effect on AQP5 protein abundance. We validated the effects of Niclosamide on endogenous AQP5 levels and in regulating cell-volume changes in response to tonicity changes. Our findings highlight a unique approach to screen for drug effects on protein abundance, and our workflow can be applied broadly to study compound effects on protein abundance in lung epithelial cells. 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. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. 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

Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs was written by Li, Zhe;Li, Xin;Huang, Yi-You;Wu, Yaoxing;Liu, Runduo;Zhou, Lingli;Lin, Yuxi;Wu, Deyan;Zhang, Lei;Liu, Hao;Xu, Ximing;Yu, Kunqian;Zhang, Yuxia;Cui, Jun;Zhan, Chang-Guo;Wang, Xin;Luo, Hai-Bin. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2020.Reference of 145040-37-5 This article mentions the following:

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It is highly desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available for other diseases and thus repurpose them for treatment of COVID-19. In general, a drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by exptl. validation, but the actual hit rate is generally rather low with traditional computational methods. Here we report a virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions and its use in identifying drugs targeting SARS-CoV-2 main protease (Mpro). The accurate FEP-ABFE predictions were based on the use of a restraint energy distribution (RED) function, making the practical FEP-ABFE-based virtual screening of the existing drug library possible. As a result, out of 25 drugs predicted, 15 were confirmed as potent inhibitors of SARS-CoV-2 Mpro. The most potent one is dipyridamole (inhibitory constant Ki = 0.04 AμM) which has shown promising therapeutic effects in subsequently conducted clin. studies for treatment of patients with COVID-19. Addnl., hydroxychloroquine (Ki = 0.36 AμM) and chloroquine (Ki = 0.56 AμM) were also found to potently inhibit SARS-CoV-2 Mpro. We anticipate that the FEP-ABFE prediction-based virtual screening approach will be useful in many other drug repurposing or discovery efforts. 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: 145040-37-5Reference 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. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. 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.Reference of 145040-37-5

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Predicting drug-metagenome interactions: Variation in the microbial β-glucuronidase level in the human gut metagenomes was written by Elmassry, Moamen M.;Kim, Sunghwan;Busby, Ben. And the article was included in PLoS One in 2021.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:

Characterizing the gut microbiota in terms of their capacity to interfere with drug metabolism is necessary to achieve drug efficacy and safety. Although examples of drug-microbiome interactions are well-documented, little has been reported about a computational pipeline for systematically identifying and characterizing bacterial enzymes that process particular classes of drugs. The goal of our study is to develop a computational approach that compiles drugs whose metabolism may be influenced by a particular class of microbial enzymes and that quantifies the variability in the collective level of those enzymes among individuals. The present paper describes this approach, with microbial β-glucuronidases as an example, which break down drug-glucuronide conjugates and reactivate the drugs or their metabolites. We identified 100 medications that may be metabolized by β-glucuronidases from the gut microbiome. These medications included morphine, estrogen, ibuprofen, midazolam, and their structural analogs. The anal. of metagenomic data available through the Sequence Read Archive (SRA) showed that the level of β-glucuronidase in the gut metagenomes was higher in males than in females, which provides a potential explanation for the sex-based differences in efficacy and toxicity for several drugs, reported in previous studies. Our anal. also showed that infant gut metagenomes at birth and 12 mo of age have higher levels of β-glucuronidase than the metagenomes of their mothers and the implication of this observed variability was discussed in the context of breastfeeding as well as infant hyperbilirubinemia. Overall, despite important limitations discussed in this paper, our anal. provided useful insights on the role of the human gut metagenome in the variability in drug response among individuals. Importantly, this approach exploits drug and metagenome data available in public databases as well as open-source cheminformatics and bioinformatics tools to predict drug-metagenome interactions. 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. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. 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.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