Month: November 2022

Potential COVID-19 Therapies from Computational Repurposing of Drugs and Natural Products against the SARS-CoV-2 Helicase was written by Piplani, Sakshi;Singh, Puneet;Winkler, David A.;Petrovsky, Nikolai. And the article was included in International Journal of Molecular Sciences in 2022.Recommanded Product: 83799-24-0 The following contents are mentioned in the article:

Repurposing of existing drugs is a rapid way to find potential new treatments for SARS-CoV-2. Here, we applied a virtual screening approach using Autodock Vina and mol. dynamic simulation in tandem to screen and calculate binding energies of repurposed drugs against the SARS-CoV-2 helicase protein (non-structural protein nsp13). Amongst the top hits from our study were antivirals, antihistamines, and antipsychotics, plus a range of other drugs. Approx. 30% of our top 87 hits had published evidence indicating in vivo or in vitro SARS-CoV-2 activity. Top hits not previously reported to have SARS-CoV-2 activity included the antiviral agents, cabotegravir and RSV-604; the NK1 antagonist, aprepitant; the trypanocidal drug, aminoquinuride; the analgesic, antrafenine; the anticancer intercalator, epirubicin; the antihistamine, fexofenadine; and the anticoagulant, dicoumarol. These hits from our in silico SARS-CoV-2 helicase screen warrant further testing as potential COVID-19 treatments. This study involved multiple reactions and reactants, such as 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0Recommanded Product: 83799-24-0).

2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising α-glucosidase inhibitors. The former are analogs of DNJ with an improved α-glucosidase inhibitory profile than that of DNJ. Boisson et al.Recommanded Product: 83799-24-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Structure-Activity Relationship and Bioactivity of Short Analogues of ELABELA as Agonists of the Apelin Receptor was written by Tran, Kien;Murza, Alexandre;Sainsily, Xavier;Delile, Eugenie;Couvineau, Pierre;Cote, Jerome;Coquerel, David;Peloquin, Maude;Auger-Messier, Mannix;Bouvier, Michel;Lesur, Olivier;Sarret, Philippe;Marsault, Eric. And the article was included in Journal of Medicinal Chemistry in 2021.Safety of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

ELABELA (ELA) is the second endogenous ligand of the apelin receptor (APJ). Although apelin-13 and ELA both target APJ, there is limited information on structure-activity relationship (SAR) of ELA. In the present work, we identified the shortest bioactive C-terminal fragment ELA23-32, which possesses high affinity for APJ (K_i 4.6 nM) and produces cardiorenal effects in vivo similar to those of ELA. SAR studies on conserved residues (Leu25, His26, Val29, Pro30, Phe31, Pro32) show that ELA and apelin-13 may interact differently with APJ. His26 and Val29 emerge as important for ELA binding. Docking and binding experiments suggest that Phe31 of ELA may bind to a tight groove distinct from that of Phe13 of Ape13, while the Phe13 pocket may be occupied by Pro32 of ELA. Further characterization of signaling profiles on the Gα_i1, Gα₁₂, and β-arrestin2 pathways reveals the importance of aromatic residue at the Phe31 or Pro32 position for receptor activation. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Safety of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N–H bond in an axial position, and the other in an equatorial position.Safety of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Structure-Activity Relationship and Bioactivity of Short Analogues of ELABELA as Agonists of the Apelin Receptor was written by Tran, Kien;Murza, Alexandre;Sainsily, Xavier;Delile, Eugenie;Couvineau, Pierre;Cote, Jerome;Coquerel, David;Peloquin, Maude;Auger-Messier, Mannix;Bouvier, Michel;Lesur, Olivier;Sarret, Philippe;Marsault, Eric. And the article was included in Journal of Medicinal Chemistry in 2021.SDS of cas: 86069-86-5 The following contents are mentioned in the article:

ELABELA (ELA) is the second endogenous ligand of the apelin receptor (APJ). Although apelin-13 and ELA both target APJ, there is limited information on structure-activity relationship (SAR) of ELA. In the present work, we identified the shortest bioactive C-terminal fragment ELA23-32, which possesses high affinity for APJ (K_i 4.6 nM) and produces cardiorenal effects in vivo similar to those of ELA. SAR studies on conserved residues (Leu25, His26, Val29, Pro30, Phe31, Pro32) show that ELA and apelin-13 may interact differently with APJ. His26 and Val29 emerge as important for ELA binding. Docking and binding experiments suggest that Phe31 of ELA may bind to a tight groove distinct from that of Phe13 of Ape13, while the Phe13 pocket may be occupied by Pro32 of ELA. Further characterization of signaling profiles on the Gα_i1, Gα₁₂, and β-arrestin2 pathways reveals the importance of aromatic residue at the Phe31 or Pro32 position for receptor activation. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5SDS of cas: 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.SDS of cas: 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Bepridil is potent against SARS-CoV-2 in vitro was written by Vatansever, Erol C.;Yang, Kai S.;Drelich, Aleksandra K.;Kratch, Kaci C.;Cho, Chia-Chuan;Kempaiah, Kempaiah Rayavara;Hsu, Jason C.;Mellott, Drake M.;Xu, Shiqing;Tseng, Chien-Te K.;Liu, Wenshe Ray. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2021.Electric Literature of C32H39NO4 The following contents are mentioned in the article:

Guided by a computational docking anal., about 30 Food and Drug Administration/European Medicines Agency (FDA/EMA)-approved small-mol. medicines were characterized on their inhibition of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). Of these small mols. tested, six displayed a concentration that inhibits response by 50% (IC50) value below 100μM in inhibiting Mpro, and, importantly, three, i.e., pimozide, ebastine, and bepridil, are basic mols. that potentiate dual functions by both raising endosomal pH to interfere with SARS-CoV-2 entry into the human cell host and inhibiting Mpro in infected cells. A live virus-based modified microneutralization assay revealed that bepridil possesses significant anti-SARS-CoV-2 activity in both Vero E6 and A459/ACE2 cells in a dose-dependent manner with low micromolar effective concentration, 50% (EC50) values. Therefore, the current study urges serious considerations of using bepridil in COVID-19 clin. tests. This study involved multiple reactions and reactants, such as 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0Electric Literature of C32H39NO4).

2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0) belongs to piperidine derivatives. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. Piperidine derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Electric Literature of C32H39NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Dependence of the inhibiting effect of bipyridines and their hydro-derivatives on configuration was written by Forostyan, Yu. N.. And the article was included in Zashchita Metallov in 1983.Category: piperidines The following contents are mentioned in the article:

The inhibiting effect of bipyridines and their hydroderivs. (concentration 0.1%) on corrosion of steel St3  [39296-41-8] in solutions of 15% H₂SO₄ at 22° and constant mixing was studied. With increasing number at H atoms in mols. of bipyridines, the corrosion inhibition coefficient and protection degree increased due to an increase in the ionization constant (i.e. increase in the amine basicity). The inhibiting effect of bipyridines was directly associated with their configuration. In bipyridine hydroderivs., ionization coefficients were different due to the mutual arrangement of amino groups in mols. The greater the distance between amino groups (adsorption centers) in the bipyridine hydroderiv. mol., the higher the basicity of the compound and, thus, the ionization constant, inhibiting coefficient, and protection degree. 4,4‘-Bipyridine  [553-26-4] and its hydroderivs. had the greatest inhibiting effect. This study involved multiple reactions and reactants, such as 3-(Piperidin-3-yl)pyridine (cas: 31251-28-2Category: piperidines).

3-(Piperidin-3-yl)pyridine (cas: 31251-28-2) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N–H bond in an axial position, and the other in an equatorial position.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Cyclic Peptidyl Inhibitors against CAL/CFTR Interaction for Treatment of Cystic Fibrosis was written by Dougherty, Patrick G.;Wellmerling, Jack H.;Koley, Amritendu;Lukowski, Jessica K.;Hummon, Amanda B.;Cormet-Boyaka, Estelle;Pei, Dehua. And the article was included in Journal of Medicinal Chemistry in 2020.Recommanded Product: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, encoding for a chloride ion channel. Membrane expression of CFTR is neg. regulated by CFTR-associated ligand (CAL). We previously showed that inhibition of the CFTR/CAL interaction with a cell-permeable peptide improves the function of rescued F508del-CFTR. In this study, optimization of the peptidyl inhibitor yielded PGD97, which exhibits a K_D value of 6 nM for the CAL PDZ domain, ≥ 130-fold selectivity over closely related PDZ domains, and a serum t_1/2 of >24 h. In patient-derived F508del homozygous cells, PGD97 (100 nM) increased short-circuit currents by ~3-fold and further potentiated the therapeutic effects of small-mol. correctors (e.g., VX-661) by ~2-fold (with an EC₅₀ of ~10 nM). Our results suggest that PGD97 may be used as a novel treatment for CF, either as a single agent or in combination with small-mol. correctors/potentiators. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Recommanded Product: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Recommanded Product: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Cyclic Peptidyl Inhibitors against CAL/CFTR Interaction for Treatment of Cystic Fibrosis was written by Dougherty, Patrick G.;Wellmerling, Jack H.;Koley, Amritendu;Lukowski, Jessica K.;Hummon, Amanda B.;Cormet-Boyaka, Estelle;Pei, Dehua. And the article was included in Journal of Medicinal Chemistry in 2020.Electric Literature of C21H21NO4 The following contents are mentioned in the article:

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, encoding for a chloride ion channel. Membrane expression of CFTR is neg. regulated by CFTR-associated ligand (CAL). We previously showed that inhibition of the CFTR/CAL interaction with a cell-permeable peptide improves the function of rescued F508del-CFTR. In this study, optimization of the peptidyl inhibitor yielded PGD97, which exhibits a K_D value of 6 nM for the CAL PDZ domain, ≥ 130-fold selectivity over closely related PDZ domains, and a serum t_1/2 of >24 h. In patient-derived F508del homozygous cells, PGD97 (100 nM) increased short-circuit currents by ~3-fold and further potentiated the therapeutic effects of small-mol. correctors (e.g., VX-661) by ~2-fold (with an EC₅₀ of ~10 nM). Our results suggest that PGD97 may be used as a novel treatment for CF, either as a single agent or in combination with small-mol. correctors/potentiators. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Electric Literature of C21H21NO4).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Electric Literature of C21H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Selection of DNA-Encoded Dynamic Chemical Libraries for Direct Inhibitor Discovery was written by Deng, Yuqing;Peng, Jianzhao;Xiong, Feng;Song, Yinan;Zhou, Yu;Zhang, Jianfu;Lam, Fong Sang;Xie, Chao;Shen, Wenyin;Huang, Yiran;Meng, Ling;Li, Xiaoyu. And the article was included in Angewandte Chemie, International Edition in 2020.Application of 86069-86-5 The following contents are mentioned in the article:

Dynamic combinatorial libraries (DCLs) is a powerful tool for ligand discovery in biomedical research; however, the application of DCLs has been hampered by their low diversity. Recently, the concept of DNA encoding has been employed in DCLs to create DNA-encoded dynamic libraries (DEDLs); however, all current DEDLs are limited to fragment identification, and a challenging process of fragment linking is required after selection. The authors report an anchor-directed DEDL approach that can identify full ligand structures from large-scale DEDLs. This method is also able to convert unbiased libraries into focused ones targeting specific protein classes. The authors demonstrated this method by selecting DEDLs against five proteins, and novel inhibitors were identified for all targets. Notably, several selective BD1/BD2 inhibitors were identified from the selections against bromodomain 4 (BRD4), an important anti-cancer drug target. This work may provide a broadly applicable method for inhibitor discovery. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Application of 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Application of 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Selection of DNA-Encoded Dynamic Chemical Libraries for Direct Inhibitor Discovery was written by Deng, Yuqing;Peng, Jianzhao;Xiong, Feng;Song, Yinan;Zhou, Yu;Zhang, Jianfu;Lam, Fong Sang;Xie, Chao;Shen, Wenyin;Huang, Yiran;Meng, Ling;Li, Xiaoyu. And the article was included in Angewandte Chemie, International Edition in 2020.Recommanded Product: 86069-86-5 The following contents are mentioned in the article:

Dynamic combinatorial libraries (DCLs) is a powerful tool for ligand discovery in biomedical research; however, the application of DCLs has been hampered by their low diversity. Recently, the concept of DNA encoding has been employed in DCLs to create DNA-encoded dynamic libraries (DEDLs); however, all current DEDLs are limited to fragment identification, and a challenging process of fragment linking is required after selection. The authors report an anchor-directed DEDL approach that can identify full ligand structures from large-scale DEDLs. This method is also able to convert unbiased libraries into focused ones targeting specific protein classes. The authors demonstrated this method by selecting DEDLs against five proteins, and novel inhibitors were identified for all targets. Notably, several selective BD1/BD2 inhibitors were identified from the selections against bromodomain 4 (BRD4), an important anti-cancer drug target. This work may provide a broadly applicable method for inhibitor discovery. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Recommanded Product: 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Piperidine derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Recommanded Product: 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Rescuing Biological Activity from Synthetic Phakellistatin 19 was written by Pelay-Gimeno, Marta;Meli, Alessandra;Tulla-Puche, Judit;Albericio, Fernando. And the article was included in Journal of Medicinal Chemistry in 2013.COA of Formula: C21H21NO4 The following contents are mentioned in the article:

Phakellistatins are families of Pro-rich cyclic peptides whose synthetic counterparts have revealed cytotoxicities that differ greatly from those displayed by their corresponding natural ones. This is also the case of the last member isolated from this family, phakellistatin 19, an octacyclopeptide containing three Pro moieties and a high percentage of apolar residues. Exhaustive NMR studies on the synthetic and natural phakellistatin 19 have been performed in order to find a plausible explanation for this intriguing behavior. Moreover, taking advantage of the phakellistatin framework, analogs with different cis/trans geometry at the key prolyl peptide bonds were designed, covering a promising conformational space that could not be reached by the natural peptide. Introduction of proline surrogates (Ψ^Me,Mepro residues) in phakellistatin 19 effectively increases the percentage of cis conformation in the final peptides, enhancing biol. activity and “rescuing” an otherwise inactive cyclopeptide. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5COA of Formula: C21H21NO4).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Piperidine derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.COA of Formula: C21H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem