Month: November 2022

Gawley, Robert E. published the artcile2-Lithio-N-methylpiperidine and 2-lithio-N-methylpyrrolidine: configurationally and chemically stable unchelated α-aminoorganolithiums, Computed Properties of 1690-74-0, the main research area is lithiomethylpiperidine preparation configurational stability; lithiomethylpyrrolidine preparation configurational stability; piperidine lithiomethyl preparation configurational stability; pyrrolidine lithiomethyl preparation configurational stability.

Enantiomerically pure 2-lithio-N-methylpiperidine and enantiomerically enriched 2-lithio-N-methylpyrrolidine (94% ee) have been made by tin-lithium exchange and evaluated for their chem. and configurational stability. Both show remarkable stability in the presence of TMEDA, resisting racemization at temperatures up to -40°.

Journal of the American Chemical Society published new progress about Configuration. 1690-74-0 belongs to class piperidines, name is Methyl 1-methylpiperidine-2-carboxylate, and the molecular formula is C8H15NO2, Computed Properties of 1690-74-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Blank, Brian R. published the artcileAntimalarial Trioxolanes with Superior Drug-Like Properties and In Vivo Efficacy, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is antimalarials endoperoxides trioxolanes lead optimization stereoselective synthesis; antimalarials; endoperoxides; lead optimization; stereoselective synthesis; trioxolanes.

The emergence of artemisinin resistance, combined with certain suboptimal properties of ozonide agents arterolane and artefenomel, has necessitated the search for new drug candidates in the endoperoxide class. Our group has focused on trioxolane analogs with substitution patterns not previously explored. Here, we describe the enantioselective synthesis of analogs bearing a trans-3” carbamate side chain and find these to be superior, both in vitro and in vivo, to the previously reported amides. We identified multiple analogs that surpass the oral efficacy of arterolane in the Plasmodium berghei model while exhibiting drug-like properties (logD, solubility, metabolic stability) similar or superior to next-generation clin. candidates like E209 and OZ609. While the preclin. assessment of new analogs is still underway, current data suggest the potential of this chemotype as a likely source of future drug candidates from the endoperoxide class.

ACS Infectious Diseases published new progress about Antimalarials. 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

Buravchenko, Galina I. published the artcileDiscovery of derivatives of 6(7)-amino-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides: novel, hypoxia-selective HIF-1α inhibitors with strong antiestrogenic potency, Quality Control of 73874-95-0, the main research area is amino phenylquinoxaline carbonitrile dioxide preparation anticancer antiestrogenic activity; Antiestrogenic potency; Antiproliferative activity; ERK 1/2 signaling pathway; HIF-1α; Hypoxia selectivity; Quinoxaline-2-carbonitrile 1,4-dioxide.

The synthesis of 3-phenylquinoxaline-2-carbonitrile 1,4-dioxides bearing cyclic diamine residues at positions 6 or 7 I (R = H, piperazin-1-yl, 3-methylpiperazin-1-yl, 3-aminopyrrolidin-1-yl, etc.; R1 = F, Cl, 3-methylpiperazin-1-yl, etc.) based on the nucleophilic substitution of halogens has been described. All synthesized 6(7)-aminoquinoxaline-2-carbonitrile 1,4-dioxides I demonstrated higher cytotoxicity and hypoxia selectivity compared to the reference agent tirapazamine against breast adenocarcinoma cell lines (MCF7, MDA-MB-231). The structure and position of the diamine residue considerably affect the antiproliferative properties of the quinoxaline-2-carbonitrile 1,4-dioxides I. The introduction of a halogen atom at position 7 in the quinoxaline ring of I (R = piperazin-1-yl; R1 = H) considerably increases the cytotoxicity of compounds I [R = piperazin-1-yl; R1 = F, Cl] under both normoxic and hypoxic conditions. However, the most hypoxia-selective derivatives were non-halogenated 7-aminosubstituted 3-phenylquinoxaline-2-carbonitrile 1,4-dioxides I (R = H; R1 = piperazin-1-yl, 3-methylpiperazin-1-yl, 3-aminopyrrolidin-1-yl, etc.). Of the 32 novel synthesized derivatives, I approx. some of the 6(7)-amino-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides demonstrated high antiproliferative potency against wild type leukemia cells K562 and drug-resistant subline K562/4 with the expression of p-glycoprotein (p-gp) compared to the reference agent doxorubicin, which exhibited one order of magnitude lower activity towards K562/4 cells than towards K562 cells. Lead compounds I (R = piperazin-1-yl; R1 = F) and I [R = H; R1 = (3S)-3-aminopyrrolidin-1-yl] inhibited HIF-1α expression and activity and induced apoptosis in hypoxic tumor cells, which was confirmed by poly(ADP-ribose)polymerase (PARP) cleavage. Moreover, I (R = piperazin-1-yl; R1 = F) and I [R = H; R1 = (3S)-3-aminopyrrolidin-1-yl] showed strong antiestrogenic potencies in MCF7 breast cancer cells. Thus, the described series of quinoxaline 1,4-dioxides I has high anticancer potential and good aqueous solubility Therefore, these compounds are promising for further drug development of hypoxia-targeted anticancer agents.

Bioorganic Chemistry published new progress about Antiestrogens. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Quality Control of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Portela, Raquel published the artcileMonolithic SiC supports with tailored hierarchical porosity for molecularly selective membranes and supported liquid-phase catalysis, Safety of Bis(2,2,6,6-tetramethylpiperidin-4-yl) decanedioate, the main research area is silicon carbide monolithic tailored hierarchical porosity liquid phase catalysis.

Monolithic support materials with the mech. resistance and thermal conductivity of SiC as well as tunable surface chem. and textural properties were developed for their use in catalytic membrane reactors. After heat treatment, the extruded SiC monoliths have a monomodal distribution of macropores of a few μm in diameter depending on the particle size of the starting material. A macroporous, defect-free, smoother skin was applied onto the external wall using a solution of sub-micrometer SiC particles. These monoliths with skin could be coated successfully with molecularly selective membranes, and thus have application in membrane reactor processes. Finally, metal oxide nanoparticles were infiltrated into the macropores to modify the surface texture and chem., allowing the immobilization of liquid phase catalysts. The resulting multimodal distribution of pore sizes could be tuned by the choice of SiC and oxide particle sizes, number of wash-coats and calcination temparature. Mesopores created between nanoparticles had diameters of roughly 40% of those of the nanoparticles. Small macropores, between 10-1000 nm, were also created, with bigger size and volume at higher calcination temparatures due to the metal oxide particles contraction. The developed materials were validated as support for PDMS membranes and for continuous gas-phase hydroformylation of 1-butene using Rh-diphosphite catalysts.

Catalysis Today published new progress about Agglomeration. 52829-07-9 belongs to class piperidines, name is Bis(2,2,6,6-tetramethylpiperidin-4-yl) decanedioate, and the molecular formula is C28H52N2O4, Safety of Bis(2,2,6,6-tetramethylpiperidin-4-yl) decanedioate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Mayer, Brian P. published the artcileStatistical analysis of the chemical attribution signatures of 3-methylfentanyl and its methods of production, Category: piperidines, the main research area is forensic chem attribution signature methylfentanyl; 3-methylfentanyl; Chemical attribution signature; Chemical forensics; Forensic attribution; Machine learning; Opioid.

Chem. attribution of the origin of an illegal drug is a key component of forensic efforts aimed at combating illicit and clandestine manufacture of drugs and pharmaceuticals. The results of these studies yield detailed information on synthesis byproducts, reagents, and precursors that can be used to identify the method of manufacture In the present work, chem. attribution signatures (CAS) associated with the synthesis of the analgesic 3-methylfentanyl, N-(3-methyl-1-phenethylpiperidin-4-yl)-N-phenylpropanamide, were investigated. Eighteen crude samples from six synthesis methods were generated, the anal. of which was used to identify signatures (i.e., chem. compounds) that were important in the discrimination of synthetic route. These methods were carefully selected to minimize the use of scheduled precursors, complicated laboratory equipment, number of steps, and extreme reaction conditions. Using gas and liquid chromatogs. combined with time-of-flight mass spectrometry (GC-QTOF and LC-QTOF) over 160 distinct species were monitored. Anal. of this combined data set was performed using modern machine learning techniques capable of reducing the size of the data set, prioritizing key chem. attribution signatures, and identifying the method of production for blindly synthesized 3-methylfentanyl materials.

Talanta published new progress about Drugs of abuse. 5773-58-0 belongs to class piperidines, name is 3-Methylpiperidin-4-one, and the molecular formula is C6H11NO, Category: piperidines.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Manz, Theresa D. published the artcileStructure-Activity Relationship Study of Covalent Pan-phosphatidylinositol 5-Phosphate 4-Kinase Inhibitors, Related Products of piperidines, the main research area is phosphatidylinositol 5 phosphate 4 kinase inhibitor THZP12 PI5P4K.

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are important mol. players in a variety of diseases, such as cancer. Currently available PI5P4K inhibitors are reversible small mols., which may lack selectivity and sufficient cellular on-target activity. In this study, we present a new class of covalent pan-PI5P4K inhibitors with potent biochem. and cellular activity. Our designs are based on THZ-P1-2, a covalent PI5P4K inhibitor previously developed in our laboratory Here, we report further structure-guided optimization and structure-activity relationship (SAR) study of this scaffold, resulting in compound 30(I), which retained biochem. and cellular potency, while demonstrating a significantly improved selectivity profile. Furthermore, we confirm that the inhibitors show efficient binding affinity in the context of HEK 293T cells using isothermal CETSA methods. Taken together, I represents a highly selective pan-PI5P4K covalent lead mol.

ACS Medicinal Chemistry Letters published new progress about Drug discovery. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Related Products of piperidines.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

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