Day: November 18, 2022

Chambers, Mark S. published the artcileSpiropiperidines as high-affinity, selective σ ligands., HPLC of Formula: 137419-24-0, the main research area is spiropiperidine selective sigma ligand; tetralin spiropiperidino selective sigma ligand; indan spiropiperidino selective sigma ligand; benzocycloheptane spiropiperidino selective sigma ligand; radioligand displacement spiropiperidinobenzocycloalkane; structure activity spiropiperidinobenzocycloalkane receptor binding.

A variety of achiral conformationally restricted spirocyclic piperidines were prepared in an attempt to investigate the functional role of the central σ recognition site. All compounds possessed a lipophilic N-substituent incorporating either a tetralin (I; n = 2, R = PhCH2, Bu, hexyl, 2-picolyl, cyclohexylmethyl, CH2CH:CH2, 2-furylmethyl, 2-thienylmethyl, CH2CH:CMe2, etc.), indan (I; n = 1, R = PhCH2, PhCH2CH2, CH2CH:CMe2, Bu, etc.), or benzocycloheptane skeleton (I; n = 3, R = PhCH2, Bu). Their in vitro affinity at the σ site was assessed in radioligand displacement experiments with guinea pig cerebellum homogenates using the σ-specific radioligand N,N-di-o-[5-3H]-tolylguanidine (II). A study of the structure-activity relationships identified the N-Bu and N-dimethylallyl substituents as the optimum groups for high affinity and selectivity at the σ site, e.g., I (n = 1, R = CH2CH:CMe2), pIC50 = 8.9 vs II and >10,000-fold selective over the dopamine D2 receptor. Such compounds are amongst the highest affinity σ ligands reported to date, with excellent selectivity over the dopamine D2 receptor, and may serve as a useful tool for exploring the physiol. role of the σ site.

Journal of Medicinal Chemistry published new progress about Antipsychotics. 137419-24-0 belongs to class piperidines, name is tert-Butyl spiro[indene-1,4′-piperidine]-1′-carboxylate, and the molecular formula is C18H23NO2, HPLC of Formula: 137419-24-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Kang, Dongwei published the artcileDiscovery of potent HIV-1 non-nucleoside reverse transcriptase inhibitors by exploring the structure-activity relationship of solvent-exposed regions I, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is HIV 1 antiHIV non nucleoside reverse transcriptase; DAPY; HIV-1; NNRTIs; solvent-exposed region I; thiophene[3,2-d]pyrimidine.

Two novel series of human immunodeficiency virus-1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs) bearing a thiophene[3,2-d]pyrimidine scaffold and sulfonamide linker in the right wing have been identified, which demonstrated activity against the wild-type (WT) HIV-1 strain in MT-4 cells with inhibitory concentrations ranging from micromolar to submicromolar. Especially, against the mutant strains K103N and E138K, most compounds exhibited more potent activity than against WT HIV-1. Compound 7(I) (EC50 = 0.014, 0.031 μM) achieved the most potent activity against the two mutants, being more effective than that of nevirapine (NVP, EC50 = 7.572, 0.190 μM) and comparable to that of etravirine (ETV, EC50 = 0.004, 0.014 μM). Mol. docking experiments on the novel analogs have also suggested that the extensive network of main chain hydrogen bonds are important in the binding mode, which may provide valuable insights for further optimization.

Chemical Biology & Drug Design published new progress about Anti-HIV agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Name: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Wang, Zhao published the artcileDiscovery of Novel Dihydrothiopyrano[4,3-d]pyrimidine Derivatives as Potent HIV-1 NNRTIs with Significantly Reduced hERG Inhibitory Activity and Improved Resistance Profiles, SDS of cas: 73874-95-0, the main research area is antiHIV antiviral resistance HIV1 infection hERG inhibition.

Enlightened by the available structural biol. information, a novel series of dihydrothiopyrano[4,3-d]pyrimidine derivatives were rationally designed via scaffold hopping and mol. hybridization strategies. Notably, compound 20a yielded exceptionally potent antiviral activities (EC50 = 4.44-54.5 nM) against various HIV-1 strains and improved resistance profiles (RF = 0.5-5.6) compared to etravirine and rilpivirine. Meanwhile, 20a exhibited reduced cytotoxicity (CC50 = 284μM) and higher SI values (SI = 5210-63992). Mol. dynamics simulations were performed to rationalize the distinct resistance profiles. Besides, 20a displayed better solubility (soluble = 12.8μg/mL) and no significant inhibition of the main CYP enzymes. Furthermore, 20a was characterized for prominent metabolic stability and in vivo safety properties. Most importantly, the hERG inhibition profile of 20a (IC50 = 19.84μM) was a remarkable improvement. Overall, 20a possesses huge potential to serve as a promising drug candidate due to its excellent potency, low toxicity, and favorable drug-like properties.

Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, SDS of cas: 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Kang, Dongwei published the artcileDevelopment of Novel Dihydrofuro[3,4-d]pyrimidine Derivatives as HIV-1 NNRTIs to Overcome the Highly Resistant Mutant Strains F227L/V106A and K103N/Y181C, Product Details of C10H20N2O2, the main research area is HIV1 NNRTI resistance F227L V106A K103N Y181C.

Here, we report the design, synthesis, structure-activity relationship studies, antiviral activity, enzyme inhibition, and druggability evaluation of dihydrofuro[3,4-d]pyrimidine derivatives as a potent class of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Compounds 14b (I) (EC50 = 5.79-28.3 nM) and 16c (II) (EC50 = 2.85-18.0 nM) exhibited superior potency against a panel of HIV-1-resistant strains. Especially, for the changeling mutations F227L/V106A and K103N/Y181C, both compounds exhibited remarkably improved activity compared to those of etravirine and rilpivirine. Moreover, 14b and 16c showed moderate RT enzyme inhibition (IC50 = 0.14-0.15 μM), which demonstrated that they acted as HIV-1 NNRTIs. Furthermore, 14b and 16c exhibited favorable pharmacokinetic and safety properties, making them excellent leads for further development.

Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Product Details of C10H20N2O2.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Hendrick, Charles E. published the artcileDirect-to-Biology Accelerates PROTAC Synthesis and the Evaluation of Linker Effects on Permeability and Degradation, Product Details of C10H20N2O2, the main research area is proteolysis targeting chimera preparation linker effect.

A platform to accelerate optimization of proteolysis targeting chimeras (PROTACs) had been developed using a direct-to-biol. (D2B) approach with a focus on linker effects. A large number of linker analogs-varying length, polarity, and rigidity-were rapidly prepared and characterized in four cell-based assays by streamlining time-consuming steps in synthesis and purification The expansive data set informs on linker structure activity relationships for in-cell E3 ligase target engagement, degradation, permeability, and cell toxicity. Unexpected aspects of linker SAR were discovered, consistent with literature reports on “”linkerol.””, and the method dramatically speeds up empirical optimization. Physicochem. property trends emerged, and the platform had the potential to rapidly expand training sets for more complex prediction models. In-depth validation studies were carried out and confirm the D2B platform was a valuable tool to accelerate PROTAC design-make-test cycles.

ACS Medicinal Chemistry Letters published new progress about Chemical library. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Product Details of C10H20N2O2.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Lv, Kai published the artcileDesign, synthesis and anti-HBV activity of NVR3-778 derivatives, Application In Synthesis of 73874-95-0, the main research area is preparation antiviral hepatitis B HBV NVR3 778 derivative; Anti-HBV activity; Capsid assembly modulators; NVR3-778; Structure modification; Sulfamoylbenzamides.

NVR3-778, one of the most advanced capsid assembly modulators (CAMs), is currently in phase II clin. trial for the treatment of HBV infection. In this study, we reported the first structure optimization of NVR3-778. Compound 2d was found to exhibit more potent anti-HBV activity (IC50: 0.25μM), lower cytotoxicity (CC50: 10.68μM) and higher selectivity index (SI: 40.72) than NVR3-778 (IC50: 0.33μM; CC50: 5.14μM; SI: 18.36) in vitro, and also display similar inhibitory effect on the assembly of HBV capsids as NVR3-778. Mol. docking further suggested that compound 2d might form a stronger interaction with core protein. Moreover, compound 2d also showed acceptable pharmacokinetic profiles. Currently compound 2d was selected as a new lead for further modifications, and studies to determine the in vivo anti-HBV studies of 2d will begin soon.

Bioorganic Chemistry published new progress about Antiviral agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Application In Synthesis of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem