Month: November 2022

Yamaki, Susumu published the artcileSynthesis and pharmacological evaluation of glycine amide derivatives as novel vascular adhesion protein-1 inhibitors without CYP3A4 and CYP2C19 inhibition, HPLC of Formula: 887425-47-0, the main research area is glycine amide derivative preparation vascular adhesion protein VAP1 inhibitor; diabetic nephropathy treatment glycine amide derivative VAP1 inhibitor; CYP2C19; CYP3A4; Diabetic nephropathy; Glycine amide; Vascular adhesion protein-1.

Vascular adhesion protein-1 (VAP-1) is a promising therapeutic target for the treatment of diabetic nephropathy. Here, the authors conducted optimization studies of the authors’ lead compound 1 (I), which the authors previously reported as a novel VAP-1 inhibitor, to enhance the inhibition of human VAP-1 and to reduce CYP3A4 and CYP2C19 inhibition. As a result, the authors identified 3-chloro-4-{4-[5-(3-{[glycyl(methyl)amino]methyl}phenyl)pyrimidin-2-yl]piperazin-1-yl}benzoic acid (17h) as a novel orally active VAP-1 inhibitor, with 14-fold increased human VAP-1 inhibitory activity compared to 1, without CYP3A4 and CYP2C19 inhibition. Oral administration of 17h significantly inhibited the progression of proteinuria in streptozotocin (STZ) induced diabetic rats at 0.3 and 1 mg/kg, suggesting that this compound has potential to be a therapeutic agent for the treatment of diabetic nephropathy.

Bioorganic & Medicinal Chemistry published new progress about Bioactive lead compounds (optimization). 887425-47-0 belongs to class piperidines, name is 1-(5-Bromopyrimidin-2-yl)piperidin-4-ol, and the molecular formula is C9H12BrN3O, HPLC of Formula: 887425-47-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Gao, Ping published the artcileNovel indolylarylsulfone derivatives as covalent HIV-1 reverse transcriptase inhibitors specifically targeting the drug-resistant mutant Y181C, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is human immunodeficiency virus 1 indolylarylsulfone cysteine phenylalanine proline; Covalent inhibitor; HIV-1; Indolylarylsulfones; NNRTIs; Y181C.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are widely used in combination therapies against HIV-1. However, emergent and transmitted drug resistance compromise their efficacy in the clin. setting. Y181C is selected in patients receiving nevirapine, etravirine and rilpivirine, and together with K103N is the most prevalent NNRTI-associated mutation in HIV-infected patients. Herein, we report on the design, synthesis and biol. evaluation of a novel series of indolylarylsulfones bearing acrylamide or ethylene sulfonamide reactive groups as warheads to inactivate Cys181-containing HIV-1 RT via a Michael addition reaction. Compounds I-7 and I-9 demonstrated higher selectivity towards the Y181C mutant than against the wild-type RT, in nucleotide incorporation inhibition assays. The larger size of the NNRTI binding pocket in the mutant enzyme facilitates a better fit for the active compounds, while stacking interactions with Phe227 and Pro236 contribute to inhibitor binding. Mass spectrometry data were consistent with the covalent modification of the RT, although off-target reactivity constitutes a major limitation for further development of the described inhibitors.

Bioorganic & Medicinal Chemistry published new progress about Antiviral agent resistance (drug-resistant). 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

Masuda, Arisa published the artcileN1-Substituted benzimidazole scaffold for farnesoid X receptor (FXR) agonists accompanying prominent selectivity against vitamin D receptor (VDR), Category: piperidines, the main research area is benzimidazole derivative preparation farnesoid vitamin D receptor osteoblast differentiation; Benzimidazole; FXR agonist; Osteoblast differentiation.

As a cellular bile acid sensor, farnesoid X receptor (FXR) participates in regulation of bile acid, lipid and glucose homeostasis, and liver protection. With respect to the bone metabolism, FXR pos. regulates bone metabolism through both bone formation and resorption of the bone remodeling pathways. Some of FXR agonists possessing isoxazole moiety are undergoing clin. trials for the treatment of non-alc. steatohepatitis. To date, therefore, the activation of FXR leads to considerable interest in FXR as potential therapeutic targets. We have identified a series of nonsteroidal FXR agonists bearing N1-Me benzimidazole and isoxazole moieties that are bridged with aromatic derivatives They showed affinity to FXR, but also weak affinity toward the vitamin D receptor (VDR) that involves regulation of calcium and phosphate homeostasis and is activated by bile acids. The deployment of FXR agonists without activity against VDR as off-target is therefore crucial in the development of FXR ligands. Our efforts focusing on increasing the agonist properties towards FXR led to the discovery of 19, which activates FXR at and below nanomolar levels (EC50 = 26.5 ± 10.5 nM TR-FRET and 0.8 ± 0.2 nM luciferase, resp.) and functions as a FXR agonist: the affinity toward FXR over eight nuclear receptors, including VDR [IC50 (VDR) / EC50 (FXR) > 5000] and TGR5, effects FXR target genes, and activates bone morphogenetic protein-2-induced differentiation of mouse bone marrow-derived mesenchymal stem cell-like ST2 cells into osteoblast.

Bioorganic & Medicinal Chemistry published new progress about Bone marrow (-derived mesenchymal stem cell). 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Category: piperidines.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Vojkovsky, Tomas published the artcileDetection of secondary amines on solid phase, Recommanded Product: 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid, the main research area is Merrifield synthesis chloranil monitoring; amine secondary detection Merrifield synthesis.

The detection of secondary amino groups in building blocks attached to solid phase using tetrachlorobenzoquinone (chloranil) was re-examined A new procedure, about ten times more sensitive than the original method, has been developed. Except for N-p-tolylglycine, all secondary amino groups that were examined were detected reliably in a substitution range down to 2.8 μeq/g. Protected imidazole in His(Trt) did not interfere with the detection method.

Peptide Research published new progress about Solid phase synthesis, solid-phase peptide synthesis. 158922-07-7 belongs to class piperidines, name is 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid, and the molecular formula is C21H21NO4, Recommanded Product: 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Reddi, Rambabu N. published the artcileSite-specific labeling of endogenous proteins using CoLDR chemistry, Application of tert-Butyl piperidin-4-ylcarbamate, the main research area is site specific labeling protein CoLDR chem PROTAC fluorescence tool; Brutons tyrosine kinase active site labeling; ibrutinib evotrutinib coupling reaction amine.

Chem. modifications of native proteins can affect their stability, activity, interactions, localization, and more. However, there are few nongenetic methods for the installation of chem. modifications at a specific protein site in cells. Here we report a covalent ligand directed release (CoLDR) site-specific labeling strategy, which enables the installation of a variety of functional tags on a target protein while releasing the directing ligand. Using this approach, we were able to label various proteins such as BTK (Bruton’s tyrosine kinase), K-RasG12C, and SARS-CoV-2 PLpro with different tags. For BTK we have shown selective labeling in cells of both alkyne and fluorophores tags. Protein labeling by traditional affinity methods often inhibits protein activity since the directing ligand permanently occupies the target binding pocket. We have shown that using CoLDR chem., modification of BTK by these probes in cells preserves its activity. We demonstrated several applications for this approach including determining the half-life of BTK in its native environment with minimal perturbation, as well as quantification of BTK degradation by a noncovalent proteolysis targeting chimera (PROTAC) by in-gel fluorescence. Using an environment-sensitive “”turn-on”” fluorescent probe, we were able to monitor ligand binding to the active site of BTK. Finally, we have demonstrated efficient CoLDR-based BTK PROTACs (DC50 < 100 nM), which installed a CRBN binder onto BTK. This approach joins very few available labeling strategies that maintain the target protein activity and thus makes an important addition to the toolbox of chem. biol. Journal of the American Chemical Society published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Application of tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Savych, Olena published the artcileOne-Pot Parallel Synthesis of 5-(Dialkylamino)tetrazoles, Product Details of C10H20N2O2, the main research area is one pot parallel combinatorial synthesis dialkylaminotetrazole; aminotetrazole library preparation; 2,2,2-trifluoroethylthiocarbamate; REAL (readily accessible) compounds; heterocyclization; tetrazoles; thiourea.

Two protocols for the combinatorial synthesis of 5-(dialkylamino)tetrazoles were developed. The best success rate (67%) was shown by the method that used primary and secondary amines, 2,2,2-trifluoroethylthiocarbamate, and sodium azide as the starting reagents. The key steps included the formation of unsym. thiourea, subsequent alkylation with 1,3-propane sultone and cyclization with azide anion. A 559-member aminotetrazole library was synthesized by this approach; the overall readily accessible (REAL) chem. space covered by the method exceeded 7 million feasible compounds

ACS Combinatorial Science published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 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

Onida, Killian published the artcileDirect Synthesis of Carbamoyl Fluorides by CO2 Deoxyfluorination, Category: piperidines, the main research area is carbamoyl fluoride synthesis carbon dioxide deoxyfluorination amine DAST; amines; carbamoyl fluorides; carbon dioxide; deoxyfluorination; fluorine.

Herein, a new concept for the direct synthesis of carbamoyl fluoride derivatives is disclosed. The developed method makes use of CO2 as an inexpensive and abundant C1 source; a variety of amines were successfully converted in the presence of a deoxyfluorinating reagent. The corresponding products were often obtained in excellent yields under mild reaction conditions (1 atm and room temperature). The reaction was easily scaled up, demonstrating the efficiency of the developed process.

Angewandte Chemie, International Edition published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Category: piperidines.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Park, Eunsun published the artcileDiscovery and Biological Evaluation of N-Methyl-pyrrolo[2,3-b]pyridine-5-carboxamide Derivatives as JAK1-Selective Inhibitors, SDS of cas: 73874-95-0, the main research area is methyl pyrrolopyridine carboxamide preparation Janus kinase inhibitor mol docking.

Janus kinase 1 (JAK1) plays a key role in most cytokine-mediated inflammatory and autoimmune responses through JAK/STAT signaling; thus, JAK1 inhibition is a promising therapeutic strategy for several diseases. Anal. of the binding modes of current JAK inhibitors to JAK isoforms allowed the design of N-alkyl-substituted 1-H-pyrrolo[2,3-b] pyridine carboxamides I (R = H, Me, cyclopropyl, cyclopentyl) as a JAK1-selective scaffold, and the synthesis of various Me amide derivatives e.g., II, provided III as a potent JAK1-selective inhibitor. In particular, the (S,S)-enantiomer of III exhibited excellent potency for JAK1 and selectivity over JAK2, JAK3, and TYK2. On investigating the effect of III on hepatic fibrosis, it was found that it reduces the proliferation and fibrogenic gene expression of TGF-β-induced hepatic stellate cells (HSCs). Specifically, III significantly inhibited TGF-β-induced migration of HSCs at 0.25μM in wound-healing assays.

Journal of Medicinal Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 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

Huo, Haibo published the artcileSynthesis and biological evaluation of novel steroidal pyrazole amides as highly potent anticancer agents, SDS of cas: 73874-95-0, the main research area is androstynyl pyrazolyl amide preparation antitumor apoptosis SAR; Amide derivatives; Antiproliferative activity; Cell cycle; Hydrochloride derivatives; Steroidal pyrazoles.

A series of thirty-six steroidal pyrazole amides, I, II [R = methylamino, 4-fluoroanilino, piperazinyl, etc.] divided into two categories based on their main skeletons were designed and synthesized via a five-step synthetic route. The final product was obtained through Pinnick oxidation of pyrazole aldehydes to yield the corresponding acids, which then underwent amidation to afford the target products efficiently under mild reaction conditions. Structures of the desired compounds were confirmed by 1H NMR, 13C NMR, high resolution mass spectrometry; X-ray structural characterization of compound II [R = piperazinyl] was also obtained. The synthesized compounds I, II were screened for their antiproliferative activity against four cancer cell lines (Pc-3 A549, Hela, HepG2) using the SRB method. Amides I,II [R = piperazinyl], and hydrochlorides II [R = 2-aminoethylamino, 2-aminopyrrolidinyl, 4-aminopiperidyl, etc.] exhibited moderate to high cytotoxic activities with IC50 values ranging from 2.05 to 8.73μM. Of note, the hydrochloride derivative II [R = piperazinyl] displayed the highest activity towards PC-3 cells with IC50 values of 2.05μM. Anal. of structure-activity relationships indicated that the presence of the diamine moiety and the aqueous solubility of the derivatives were vital factors for antiproliferative potency. Furthermore, mol. hydrochloride II [R = piperazinyl] induced PC-3 cells apoptosis and arrested cell cycle at G1 phase in a dose-dependent manner.

Steroids published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 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