Month: November 2022

Zhang, Jin published the artcileDesign, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells, Synthetic Route of 73874-95-0, the main research area is pyrazolopyrimidine preparation PAK1 inhibitor mol docking; Apoptosis; Breast cancer; High-throughput screening; Migration; PAK1 inhibitor.

P21-activated kinase 1 (PAK1) is associated with cell proliferation, survival and migration. Deregulation of PAK1 activity is involved in various human diseases, including cancer, inflammation, and neurol. disorders. Using a high-throughput virtual screening, we identified the 1H-pyrazolo [3,4-d]pyrimidine scaffold as a promising lead for targeting PAK1. A novel potent PAK1 inhibitor, (I), was discovered, which presented an IC50 value of 174 nM with a good selectivity. In addition, compound Icould inhibit PAK1-ERK signaling to suppress MDA-MB-231 cells proliferation with an IC50 value of 3.48μM for 48 h. Subsequently, compound Iwas documented to induce cell apoptosis. Interestingly, according to the RNASeq-based analyses, substantiated that compound Iinduced significant ER-Stress, suppressed migration via FOXO3 activation, JNK1/2, ERK1/2 and AKT signaling inhibition. Together, these results demonstrate that compound Iis a novel PAK1 inhibitor triggering apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells, which may provide a candidate lead for the development of novel potent inhibitors of PAK1.

European Journal of Medicinal Chemistry published new progress about Acid chlorides 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, Synthetic Route of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Qian, Yuqing published the artcileDesign and synthesis of N-(1-(6-(substituted phenyl)-pyridazin-3-yl)-piperidine-3-yl)-amide derivatives as JMJD6 inhibitors, Quality Control of 73874-95-0, the main research area is pyridazinyl piperidinyl amide preparation antitumor inhibitor docking; Breast cancer, antitumor agent; JMJD6 inhibitor.

JMJD6 is a member of the JmjC domain-containing family and has been identified as a promising therapeutic target for treating estrogen-induced and triple-neg. breast cancer. To develop novel anti-breast cancer agents, a class of N-(1-(6-(substituted phenyl)-pyridazine-3-yl)-piperidine-3-yl)-amide derivatives I [R = 3-(pyridin-3-ylcarbonylamino), 4-(4-methoxyphenylcarbonylamino), 3-(4-methoxyphenylcarbonylamino), etc.; R1 = MeO, Cl, Et, NH2, NHBoc, NHMe] as potential JMJD6 inhibitors was synthesized. Among them, the anti-cancer compound I [R = 3-((4-methoxyphenyl)amidyl), etc.; R1 = NHMe] was an excellent JMJD6 binder (KD = 0.75 ± 0.08μM). It could upregulate the mRNA and protein levels of p53 and its downstream effectors p21 and PUMA by inhibiting JMJD6. Besides, compound I [R = 3-(4-methoxyphenylcarbonylamino); R1 = NHMe] displayed potent anti-proliferative activities against tested breast cancer cells by the induction of cell apoptosis and cell cycle arrest. Significantly, compound I [R = 3-(4-methoxyphenylcarbonylamino); R1 = NHMe] also promoted a remarkable reduction in tumor growth, with a TGI value of 66.6% (50 mg/kg, i.p.). Taken together, this findings suggest that compound I [R = 3-(4-methoxyphenylcarbonylamino); R1 = NHMe] is a potent JMJD6 inhibitor bearing a new scaffold acting as a promising drug candidate for the treatment of breast cancer.

Bioorganic Chemistry published new progress about Acid chlorides 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, Quality Control of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Kim, WooChan published the artcileDiscovery of Novel Pyrimidine-Based Capsid Assembly Modulators as Potent Anti-HBV Agents, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is pyrimidine preparation antiviral activity SAR pharmacokinetic study mol docking; structure property relationship.

In this study, novel potent pyrimidine derivatives I (R1 = SMe, SO2Me; R2 = [2-(pyridin-3-ylformamido)ethyl]aminyl, 3-Cl-4-FC6H3NH, 4-aminopiperidin-1-yl, etc.; R3 = [4-(morpholin-4-yl)phenyl]aminyl, C6H5NH, 3-Br-4-FC6H3NH, etc.) as core assembly modulators were synthesized and their antiviral effects were evaluated in in vitro and in vivo biol. experiments One of the synthesized derivatives, compound I (R1 = SO2Me; R2 = 4-aminopiperidin-1-yl; R3 = 3-Cl-4-F-C6H3NH) displayed potent inhibitory effects in the in vitro assays (52% inhibition in the protein-based assay at 100 nM and an IC50 value of 181 nM in the serum HBV DNA quantification assay). Moreover, treatment with compound I (R1 = SO2Me; R2 = 4-aminopiperidin-1-yl; R3 = 3-Cl-4-F-C6H3NH) for 5 wk significantly decreased serum levels of HBV DNA levels (3.35 log reduction) in a human liver-chimeric uPA/SCID mouse model, and these effects were significantly increased when I (R1 = SO2Me; R2 = 4-aminopiperidin-1-yl; R3 = 3-Cl-4-F-C6H3NH) was combined with tenofovir, a nucleotide analog inhibitor of reverse transcriptase used for the treatment of HBV infection.

Journal of Medicinal Chemistry published new progress about Acid chlorides 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, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Zhou, Xueying published the artcileHaloamines as Bifunctional Reagents for Oxidative Aminohalogenation of Maleimides, Application of tert-Butyl piperidin-4-ylcarbamate, the main research area is chloro amino pyrroledione green preparation; maleimide haloamine oxidative aminohalogenation copper catalyst.

An unprecedented copper-catalyzed oxidative aminohalogenation of electron-deficient maleimides with secondary amines and NXS (X = Cl, Br, I) was developed to form pyrrole-2,5-diones I [R1 = Me, R2 = n-pentyl, Bn, CH2(4-ClC6H4), etc.; R1R2 = CH2CH2CH2, CH2CH2OCH2CH2, CH2(CH2)3CH2, etc.] in which the N-X bonds generated in situ were used as difunctionalized reagents. The distinctive features of this multicomponent reaction included a simple green catalytic system, a spectral substrate range and the late-stage modification of drug mols. Most importantly, this umpolung radical cascade strategy exploits the in situ formation of N-iodoamines that enabled efficient alkene aminoiodination.

Organic Letters published new progress about Aliphatic 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

Tang, Kai published the artcileStructure-based design, synthesis and biological evaluation of aminopyrazines as highly potent, selective, and cellularly active allosteric SHP2 inhibitors, Synthetic Route of 73874-95-0, the main research area is aminopyrazine preparation cellularly active allosteric SHP2 inhibitor; Aminopyrazines; Dephosphorylase; SHP2 inhibitor.

Src homol.-2-containing protein tyrosine phosphatase 2 (SHP2) encoded by the proto-oncogene PTPN11 is the first identified non-receptor protein tyrosine phosphatase. SHP2 dysregulation contributes to the pathogenesis of different cancers, making SHP2 a promising therapeutic target for cancer therapy. In this article, authors report the structure-guided design based on the well-characterized SHP2 inhibitor SHP099, extensive structure-activity relationship studies (SARs) of aminopyrazines, biochem. characterization and cellular potency. These medicinal chem. efforts lead to the discovery of the lead compound TK-453 I, which potently inhibits SHP2 (SHP2WT IC50 = 0.023μM, ΔTm = 7.01°C) in a reversible and noncompetitive manner. Compound I exhibits high selectivity over SHP2PTP, SHP1 and PTP1B, and may bind at the “”tunnel”” allosteric site of SHP2 as SHP099. As the key pharmacophore, the aminopyrazine scaffold not only reorganizes the cationic-π stacking interaction with R111 via the novel hydrogen bond interaction between the S atom of thioether linker and T219, but also mediates a hydrogen bond with E250. In vitro studies indicate that I inhibits proliferation of HeLa, KYSE-70 and THP-1 cells moderately and induces apoptosis of Hela cells. Further mechanistic studies suggest that I can decrease the phosphorylation levels of AKT and Erk1/2 in HeLa and KYSE-70 cells.

European Journal of Medicinal Chemistry published new progress about Arylboronic acids 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, Synthetic Route of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Chen, Yiding published the artcileDirect Copper-Catalyzed Three-Component Synthesis of Sulfonamides, SDS of cas: 132431-09-5, the main research area is aryl heteroaryl alkenyl sulfonamide preparation; copper catalyst coupling boronic acid amine DABSO; secondary cyclic acyclic amine aniline coupling boronic acid DABSO.

Sulfonamides such as N-(phenylsulfonyl)morpholine were prepared in one step by coupling of aryl-, heteroaryl-, and alkenylboronic acids such as phenylboronic acid with cyclic and acyclic alkyl secondary amines such as morpholine and primary anilines and the bis(sulfur dioxide) complex of DABCO (DABSO) in the presence of Cu(OTf)2 and 4,4′-dimethoxy-2,2′-bipyridine in DMSO. The method was used on gram scale and was used to prepare sulfonamides from drugs and drug fragments.

Journal of the American Chemical Society published new progress about Anilines Role: RCT (Reactant), RACT (Reactant or Reagent) (primary). 132431-09-5 belongs to class piperidines, name is Benzyl (piperidin-4-ylmethyl)carbamate, and the molecular formula is C14H20N2O2, SDS of cas: 132431-09-5.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Verschueren, Rik H. published the artcileSolvent-free N-Boc deprotection by ex situ generation of hydrogen chloride gas, Synthetic Route of 73874-95-0, the main research area is amine hydrochloride salt preparation green chem; tertbutyl carbamate deprotection.

An efficient, scalable and sustainable method for the quant. deprotection of the tert-Bu carbamate (N-Boc) protecting group is described, using down to near-stoichiometric amounts of hydrogen chloride gas in solvent-free conditions. The ex situ generation of hydrogen chloride gas from sodium chloride and sulfuric acid in a two-chamber reactor, introducing a straightforward method for controlled and stoichiometric release of HCl gas were demonstrated. The solvent-free conditions allow deprotection of a wide variety of N-Boc derivatives e.g., N-Boc benzylamine to obtain the hydrochloride salts in e.g., benzylamine hydrochloride quant. yields. The procedure obviates the need for any work-up or purification steps providing an uncomplicated green alternative to standard methods. Due to the solvent-free, anhydrous conditions, this method shows high tolerance towards acid sensitive functional groups and furnishes expanded functional group orthogonality.

Organic & Biomolecular Chemistry published new progress about Amines, salts Role: SPN (Synthetic Preparation), PREP (Preparation). 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Synthetic Route of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Tao, Shao-Kun published the artcileElectrochemical Cross-Dehydrogenative Aromatization Protocol for the Synthesis of Aromatic Amines, Category: piperidines, the main research area is cyclohexanone morpholine electrochem cross dehydrogenative aromatization; aryl amine preparation.

The first example of electrochem. cross-dehydrogenative aromatization (ECDA) reaction of saturated cyclohexanones and amines to construct anilines without addnl. metal catalysts and chem. oxidants. This reaction exhibited a broad scope of cyclohexanones including heterocyclic ketones, affording a variety of aromatic amines with various functionalities, and shows great potential in the synthesis of biol. active compounds

Organic Letters published new progress about Aromatic amines Role: SPN (Synthetic Preparation), PREP (Preparation). 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

Watterson, Scott H. published the artcileDiscovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid in Vivo Inactivation of Bruton’s Tyrosine Kinase (BTK), Name: (R)-Benzyl piperidin-3-ylcarbamate, the main research area is covalent irreversible inhibitor Bruton’s tyrosine kinase Branebrutinib pharmacokinetics.

Bruton’s tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR) mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fcγ receptor in monocytes, the Fcε receptor in granulocytes, and the RANK receptor in osteoclasts. As a result, pharmacol. inhibition of BTK is anticipated to provide an effective strategy for the clin. treatment of autoimmune diseases such as rheumatoid arthritis and lupus. This article will outline the evolution of our strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose. With excellent in vivo efficacy and a very desirable tolerability profile, 5a (branebrutinib, BMS-986195) has advanced into clin. studies.

Journal of Medicinal Chemistry published new progress about Bruton tyrosine kinase inhibitors (a covalent, irreversible inhibitor). 478646-32-1 belongs to class piperidines, name is (R)-Benzyl piperidin-3-ylcarbamate, and the molecular formula is C13H18N2O2, Name: (R)-Benzyl piperidin-3-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Hegedus, Louis S. published the artcilePhotolytic reactions of chromium aminocarbene complexes. Conversion of amides to α-amino acids, Quality Control of 1690-74-0, the main research area is chromium aminocarbene complex photochem carbonylation; amide complexation pentacarbonylchromium dianion; stereochem carbonylation chromium aminocarbene complex.

A variety of tertiary amides were converted to chromium aminocarbene complexes by reaction with Na2Cr(CO)5 and Me3SiCl. Photolysis of these carbene complexes in MeOH or Me3COH produced α-amino esters in good to excellent yields. Aminocarbene complexes containing chiral oxazolidine groups were synthesized and photolyzed in alc. to produce chiral α-amino esters in 50-93% diastereomeric excesses. Pentacarbonyl[(dibenzylaminomethyl)carbene]chromium(0) was prepared in high yield by the N-benzylation of the corresponding monobenzyl amino complex. Base-assisted alkylation of the Me group with a variety of halides followed by photolysis in MeOH produced the alkylated alanine Me ester in excellent overall yield. Other aminocarbene complexes underwent similar reactions. With chiral, optically active aminocarbene complexes, the alkylated alanine derivative was produced with high diastereoselectivity.

Journal of the American Chemical Society published new progress about Amino acid esters Role: SPN (Synthetic Preparation), PREP (Preparation). 1690-74-0 belongs to class piperidines, name is Methyl 1-methylpiperidine-2-carboxylate, and the molecular formula is C8H15NO2, Quality Control of 1690-74-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem