Category: 914610-39-2

Devine, William published the artcileProtozoan parasite growth inhibitors discovered by cross-screening yield potent scaffolds for lead discovery, Formula: C17H27BN2O4S, the publication is Journal of Medicinal Chemistry (2015), 58(14), 5522-5537, database is CAplus and MEDLINE.

Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases. Building on the previous identification of NEU-617 as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), the authors have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, the authors describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors’ biol. activities against these parasites. In doing this, the authors have identified several potent proliferation inhibitors for each pathogen, such as NEU-924, I, for T. cruzi and NEU-1017, II, for L. major and P. falciparum.

Journal of Medicinal Chemistry published new progress about 914610-39-2. 914610-39-2 belongs to piperazines, auxiliary class Piperazine,Boronic acid and ester,Sulfamide,Benzene,Piperazine,Boronate Esters,Boronic acid and ester,, name is 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine, and the molecular formula is C17H27BN2O4S, Formula: C17H27BN2O4S.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Gobbo, Dorothea published the artcileInvestigating Drug-Target Residence Time in Kinases through Enhanced Sampling Simulations, Recommanded Product: 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine, the publication is Journal of Chemical Theory and Computation (2019), 15(8), 4646-4659, database is CAplus and MEDLINE.

It is widely accepted that drug-target association and dissociation rates directly affect drug efficacy and safety. To rationally optimize drug binding kinetics, one must know the at. arrangement of the protein-ligand complex during the binding/unbinding process in order to detect stable and metastable states. Whereas exptl. approaches can determine kinetic constants with fairly good accuracy, computational approaches based on mol. dynamics (MD) simulations can deliver the atomistic details of the unbinding process. Furthermore, they can also be utilized prospectively to predict residence time (i.e., the inverse of unbinding kinetics constant, k_off) with an acceptable level of accuracy. Here, we report a novel method based on adiabatic bias MD with an electrostatics-like collective variable (dubbed elABMD) for sampling protein-ligand dissociation events in two kinases. elABMD correctly ranked a ligand series on glucokinase, in agreement with exptl. data and previous calculations Subsequently, we applied the new method prospectively to a congeneric series of GSK-3β inhibitors. For this series, new crystal structures were generated and the residence time was exptl. measured with surface plasmon resonance (SPR). There was good agreement between computational predictions and exptl. measures, suggesting that elABMD is an innovative and efficient tool for calculating residence times.

Journal of Chemical Theory and Computation published new progress about 914610-39-2. 914610-39-2 belongs to piperazines, auxiliary class Piperazine,Boronic acid and ester,Sulfamide,Benzene,Piperazine,Boronate Esters,Boronic acid and ester,, name is 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine, and the molecular formula is C17H27BN2O4S, Recommanded Product: 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Bachovchin, Kelly A. published the artcileImprovement of aqueous solubility of lapatinib-derived analogues: identification of a quinolinimine lead for human African trypanosomiasis drug development, Synthetic Route of 914610-39-2, the publication is Journal of Medicinal Chemistry (2019), 62(2), 665-687, database is CAplus and MEDLINE.

Lapatinib, an approved epidermal growth factor receptor inhibitor, was explored as a starting point for the synthesis of new hits against Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). Previous work culminated in I, which was part of a series typically associated with poor aqueous solubility In this report, we present various medicinal chem. strategies that were used to increase the aqueous solubility and improve the physicochem. profile without sacrificing antitrypanosomal potency. To rank trypanocidal hits, a new assay (summarized in a cytocidal effective concentration (CEC₅₀)) was established, as part of the lead selection process. Increasing the sp³ carbon content of I resulted in II (0.19 μM EC₅₀ against T. brucei and 990 μM aqueous solubility). Further chem. exploration of II yielded III, a trypanocidal quinolinimine (EC₅₀: 0.013 μM; aqueous solubility: 880 μM; and CEC₅₀: 0.18 μM). Compound III reduced parasitemia 10⁹ fold in trypanosome-infected mice; it is an advanced lead for HAT drug development.

Journal of Medicinal Chemistry published new progress about 914610-39-2. 914610-39-2 belongs to piperazines, auxiliary class Piperazine,Boronic acid and ester,Sulfamide,Benzene,Piperazine,Boronate Esters,Boronic acid and ester,, name is 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine, and the molecular formula is C17H27BN2O4S, Synthetic Route of 914610-39-2.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics