Day: November 15, 2022

Chiaramonte, Niccolo published the artcileSulfonamides incorporating piperazine bioisosteres as potent human carbonic anhydrase I, II, IV and IX inhibitors, Related Products of piperidines, the main research area is preparation sulfonamide piperazine bioisostere carbonic anhydrases inhibitor structure; Carbonic anhydrase; Carbonic anhydrase inhibitors; Isoform selectivity; Piperazine bioisosteres; Piperazines; Sulfonamides.

Starting from the mol. simplification of (R) 4-(3,4-dibenzylpiperazine-1-carbonyl)benzenesulfonamide 9a, a compound endowed with selectivity for human Carbonic Anhydrase (hCA) IV, a series of piperazines and 4-aminopiperidines carrying a 4-sulfamoylbenzamide moiety as Zn-binding group have been designed and tested on human isoforms hCA I, II, IV and IX, using a stopped flow CO2 hydrase assay. The aim of the work was to derive structure-activity relationships useful for designing isoform selective compounds These structural modifications changed the selectivity profile of the analogs from hCA IV to hCA I and II, and improved potency. Several of the new compounds showed subnanomolar activity on hCA II. X-ray crystallog. of ligand-hCAII complexes was used to compare the binding modes of the new piperazines and the previously synthesized 2-benzyl-piperazine analogs, explaining the inhibition profiles.

Bioorganic Chemistry published new progress about Carbonic anhydrase inhibitors. 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

Kalinin, Stanislav published the artcileHighly hydrophilic 1,3-oxazol-5-yl benzenesulfonamide inhibitors of carbonic anhydrase II for reduction of glaucoma-related intraocular pressure, Formula: C10H20N2O2, the main research area is glaucoma intraocular pressure CA inhibitors hydrophilicity non corneal absorption; Carbonic anhydrase inhibitors; Glaucoma; Hydrophilicity; Intraocular delivery; Intraocular pressure; Non-corneal absorption.

Four inhibitors of human carbonic anhydrase II (hCA II) were designed based on the previously reported subnanomolar 1,3-oxazole-based sulfonamide inhibitors of the enzyme to incorporate primary and secondary amine functionality in the carboxamide side chain. The new hydrophilic compounds were found to inhibit the target isoform in sub-nanomolar to low nanomolar range with a good degree of selectivity to several other hCA isoforms. The hydrophilic character of these compounds is advantageous for intraocular residence time but not for corneal permeability which generally requires that a drug be sufficiently lipophilic. Two of the four compounds investigated, however, were found to exert comparable efficacy as 1% eye drops in PBS to that of the clin. used 2% dorzolamide (Trusopt) eye drops. This indicated that the absorption of the compounds may occur via alternative route across conjunctiva and sclera.

Bioorganic & Medicinal Chemistry published new progress about Carbonic anhydrase inhibitors. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Formula: C10H20N2O2.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Amato, George published the artcileFunctionalized 6-(Piperidin-1-yl)-8,9-Diphenyl Purines as Peripherally Restricted Inverse Agonists of the CB1 Receptor, HPLC of Formula: 73874-95-0, the main research area is piperidinyl diphenyl purine preparation CB1 receptor alc liver steatosis.

Peripherally restricted CB1 receptor antagonists may be useful in treating metabolic syndrome, diabetes, liver diseases, and gastrointestinal disorders. Clin. development of the centrally acting CB1 inverse agonist otenabant (1) was halted due to its potential of producing adverse effects. SAR studies of 1 are reported herein with the objective of producing peripherally restricted analogs. Crystal structures of hCB1 and docking studies with 1 indicate that the piperidine group could be functionalized at the 4-position to access a binding pocket that can accommodate both polar and nonpolar groups. The piperidine is studied as a linker, functionalized with alkyl, heteroalkyl, aryl, and heteroaryl groups using a urea connector. Orally bioavailable and peripherally selective compounds have been produced that are potent inverse agonists of hCB1 with exceptional selectivity for hCB1 over hCB2. Compound 38 blocked alc.-induced liver steatosis in mice and has good ADME properties for further development.

Journal of Medicinal Chemistry published new progress about Alcoholic fatty liver disease. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, HPLC of Formula: 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Wang, Ying published the artcileThe Use of Potassium/Sodium Nitrite as a Nitrosating Agent in the Electrooxidative N-Nitrosation of Secondary Amines, Application In Synthesis of 73874-95-0, the main research area is nitroso compound preparation; secondary amine potassium nitrite electrooxidative nitrosation.

The electrochem. N-nitrosation of secondary amines, e.g., 1-phenylpiperazine using widely available sodium/potassium nitrite as a nitrosating agent has been described. This approach not only eliminates the need for using a combination of sodium/potassium and a strong acid but also has good functional group tolerance. The reaction is compatible with the late-stage modification of pharmaceutical compounds, e.g., I and could be conducted in gram scale with a high reaction efficiency. Preliminary mechanistic studies indicate that the N-nitrosation occurs via the anodic oxidation of KNO2 into an NO2 radical which is then transformed into an NO+ cation.

European Journal of Organic Chemistry published new progress about Nitrosation (electrooxidative). 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

Ngo, Huy X. published the artcilePotent 1,2,4-Triazino[5,6b]indole-3-thioether Inhibitors of the Kanamycin Resistance Enzyme Eis from Mycobacterium tuberculosis, Recommanded Product: 2-(Chloromethyl)-1-methylpiperidine hydrochloride, the main research area is triazinoindole thioether kanamycin resistance aminoglycoside acetyltransferase Eis Mycobacterium tuberculostatic; aminoglycoside resistance; antitubercular agent; combination therapy; high-throughput screen; structure-activity relationship (SAR).

A common cause of resistance to kanamycin (KAN) in tuberculosis is overexpression of the enhanced intracellular survival (Eis) protein. Eis is an acetyltransferase that multiacetylates KAN and other aminoglycosides, rendering them unable to bind the bacterial ribosome. By high-throughput screening, a series of substituted 1,2,4-triazino[5,6b]indole-3-thioether mols. were identified as effective Eis inhibitors. Herein, the authors purchased 17 and synthesized 22 new compounds, evaluated their potency, and characterized their steady-state kinetics. Four inhibitors were found not only to inhibit Eis in vitro, but also to act as adjuvants of KAN and partially restore KAN sensitivity in a Mycobacterium tuberculosis KAN-resistant strain in which Eis is upregulated. A crystal structure of Eis in complex with a potent inhibitor and Co-A shows that the inhibitors bind in the aminoglycoside binding site snugly inserted into a hydrophobic cavity. These inhibitors will undergo preclin. development as novel KAN adjuvant therapies to treat KAN-resistant tuberculosis.

ACS Infectious Diseases published new progress about Antibacterial agent resistance. 27483-92-7 belongs to class piperidines, name is 2-(Chloromethyl)-1-methylpiperidine hydrochloride, and the molecular formula is C7H15Cl2N, Recommanded Product: 2-(Chloromethyl)-1-methylpiperidine hydrochloride.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Bongard, Jens published the artcileChemical Validation of DegS As a Target for the Development of Antibiotics with a Novel Mode of Action, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is DegS drug target antibiotic preparation; antibiotics; drug discovery; small molecules; synergism; synthesis.

Despite the availability of hundreds of antibiotic drugs, infectious diseases continue to remain one of the most notorious health issues. In addition, the disparity between the spread of multidrug-resistant pathogens and the development of novel classes of antibiotics exemplify an important unmet medical need that can only be addressed by identifying novel targets. Herein we demonstrate, by the development of the first in vivo active DegS inhibitors based on a pyrazolo[1,5-a]-1,3,5-triazine scaffold, that the serine protease DegS and the cell envelope stress-response pathway σE represent a target for generating antibiotics with a novel mode of action. Moreover, DegS inhibition is synergistic with well-established membrane-perturbing antibiotics, thereby opening promising avenues for rational antibiotic drug design.

ChemMedChem published new progress about Antibacterial agent resistance. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Ren, Chaowei published the artcileStructure-based discovery of SIAIS001 as an oral bioavailability ALK degrader constructed from Alectinib, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is anaplastic lymphoma kinase alectinib preparation anticancer oral bioavailability; Alectinib; Anaplastic large-cell lymphomas; Anaplastic lymphoma kinase; CRBN; Oral bioavailability; Proteolysis targeting chimeras.

Fusion proteins of the anaplastic lymphoma kinase (ALK) are promising therapeutic targets for cancer and other human diseases, especially for non-small cell lung cancer (NSCLC) and anaplastic large-cell lymphomas (ALCLs). Herein a structure-based design, synthesis, and evaluation of ALK PROTACs (proteolysis-targeting chimeras) based on Alectinib, as the warhead were described. CRBN ligands as the E3 ligase moiety were screened first, used to obtain a series of potent ALK degraders based on different CRBN ligands, and exemplified by SIAIS091 and SIAIS001 with lenalidomide/thalidomide-based linkers. Both of them induced effective ALK degradation at low nanomolar concentrations in cells, and showed much better growth inhibition effects than Alectinib. SIAIS091 or SIAIS001 also promoted cell cycle arrest in G1/S phase. Finally, SIAIS001 exhibited good oral bioavailability in Pharmacokinetics study.

European Journal of Medicinal Chemistry published new progress about Anaplastic large-cell lymphoma. 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

Tata, James R. published the artcileThe synthesis and activity of spiroindane growth hormone secretagogues, Synthetic Route of 137419-24-0, the main research area is spiroindane preparation growth hormone secretagogue structure.

The synthesis and activities of a series of spiroindane growth hormone secretagogues is reported. Modification of the benzylic position of the spiroindane has resulted in a dramatic increase in potency resulting in sub-nanomolar peptidomimetic growth hormone secretagogues. In vivo data demonstrating the good oral activity of these analogs is reported.

Bioorganic & Medicinal Chemistry Letters published new progress about Structure-activity relationship. 137419-24-0 belongs to class piperidines, name is tert-Butyl spiro[indene-1,4′-piperidine]-1′-carboxylate, and the molecular formula is C18H23NO2, Synthetic Route of 137419-24-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Tanaka, Akito published the artcileStudies on anti-platelet agents. IV. A series of 2-substituted 4,5-bis(4-methoxyphenyl)pyrimidines as novel anti-platelet agents, Formula: C12H20Cl2N2, the main research area is pyrimidine bismethoxyphenyl antiplatelet agent; vasodilatory activity pyrimidine bismethoxyphenyl; cyclooxygenase inhibitor pyrimidine bismethoxyphenyl.

The syntheses and structure-activity relationships of a series of 2-substituted 4,5-bis(4-methoxyphenyl)pyrimidines, designed on the basis of structural analyses of several cyclooxygenase (CO) inhibitors, and their derivatives as anti-platelet agents based on CO inhibition are described. Among them, 4,5-bis(4-methoxyphenyl)-2-morpholinopyrimidine and 4,5-bis(4-methoxyphenyl)-2-(3,5-dimethylmorpholin-4-yl)pyrimidine showed potent inhibitory activity on malondialdehyde, formed by the CO-catalyzed oxygenation of arachidonic acid (A.A.) in prostanoids, production in vitro (73.4% inhibition at 10-8 M and IC50 = 1.4 × 10-8 M, resp.). Certain compounds were also examined in ex vivo studies. Of these compounds, 4,5-bis(4-methoxyphenyl)-2-(1-methyl-1,2,3,6,-tetrahydropyrid-4-yl)pyrimidine (11a) exhibited potent and long-lasting anti-platelet activity ex vivo, i.e., 11a showed 97% inhibition of platelet aggregation induced by A.A. even 24 h after oral administration of 3.2 mg/kg in guinea pigs, and 60-70% inhibition at 6 h after lower doses (1.0 mg/kg). The ex vivo activity of 11a is more than three times that of aspirin (aspirin showed 81% inhibitory activity on platelet aggregation induced by A.A. at 6 h after oral administration at 10 mg/kg is this study). Compound 11a also showed vasodilatory activity (ED50 = 5.3 × 10-6 M, while aspirin has no vasodilatory activity at 6.0 × 10-4 M).

Chemical & Pharmaceutical Bulletin published new progress about Platelet aggregation inhibitors. 1205-72-7 belongs to class piperidines, name is 1-Benzylpiperidin-4-amine dihydrochloride, and the molecular formula is C12H20Cl2N2, Formula: C12H20Cl2N2.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Du, Qianming published the artcileDiscovery of phosphonamidate IDO1 inhibitors for the treatment of non-small cell lung cancer, SDS of cas: 73874-95-0, the main research area is phosphonamidate IDO1 inhibitor preparation antitumor human lung non small; Epacadostat; IDO1 inhibitors; IDO2; Phosphonamidate ester; TDO.

Targeting indoleamine 2,3-dioxygenase 1 (IDO1) has been identified as an attractive approach for the development of cancer immunotherapy. In this study, a series of phosphonamidate ester containing compounds were designed, synthesized and evaluated for their inhibitory activities against IDO1. Among them, compounds 16, 17, and 26 with good IDO1 inhibitory (HeLa IDO1 IC50 = 10-21 nM, hIDO1 IC50 = 78-121 nM) activities were selected for further investigation and showed good physicochem. properties. Furthermore, based on comparable PK profile and excellent IDO2/TDO inhibitory potency, representative compound 16 was selected for further bio-evaluation and characterized with good efficacy in suppressing lung metastasis (77% inhibition rate) of Lewis cells in vivo. Thus, compound 16 could be a potential and efficacious agent for further evaluation.

European Journal of Medicinal Chemistry published new progress about Antitumor agents (cervix, lung). 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