Day: November 17, 2022

Zhu, Shulei published the artcileDesign, Synthesis, and Biological Evaluation of HSP90 Inhibitor-SN38 Conjugates for Targeted Drug Accumulation, Related Products of piperidines, the main research area is cancer HSP90 inhibitor SN38 antitumor toxicity pharmacokinetic.

Herein, a series of HSP90 inhibitor-SN38 conjugates through ester and carbamate linkage in the 20-OH and 10-OH positions of SN38 were developed for improving the tumor-specific penetration and accumulation of SN38 via extracellular HSP90 (eHSP90)-mediated endocytosis. Mechanistic analyses confirmed that these novel conjugates could bind to eHSP90 and be selectively internalized into the tumor cells, which led to prolonged tumor regression in multiple models of cancer. Among all studied conjugates, compound 18b(I) showed excellent in vitro activities, including acceptable HSP90α affinity and potent antitumor activity. Moreover, compound 18b exhibited superior antitumor activity and low toxicity in HCT116 and Capan-1 xenograft models. Pharmacokinetic analyses in HCT116 and Capan-1 xenografts further confirmed that compound 18b treatment could lead to effective cleavage and extended SN38 exposure at tumor sites. All these encouraging data indicate that this compound is a promising new candidate for cancer therapy and merits further chem. and biol. evaluation.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 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

Yamada, Ken published the artcileDiscovery of a Novel Piperidine-Based Inhibitor of Cholesteryl Ester Transfer Protein (CETP) That Retains Activity in Hypertriglyceridemic Plasma, Application of 1-N-Boc-2-Ethylpiperidin-4-one, the main research area is CETP inhibition piperidine analog hypertriglyceridemic plasma activity; piperidine analog preparation hypertriglyceridemic plasma activity.

Herein we describe the discovery and characterization of a novel, piperidine-based inhibitor of cholesteryl ester transfer protein (CETP) with a core structure distinct from other reported CETP inhibitors. A versatile synthesis starting from 4-methoxypyridine enabled an efficient exploration of the SAR, giving a lead mol. with potent CETP inhibition in human plasma. The subsequent optimization focused on improvement of pharmacokinetics and mitigation of off-target liabilities, such as CYP inhibition, whose improvement correlated with increased lipophilic efficiency. The effort led to the identification of an achiral, carboxylic acid-bearing compound I (TAP311) with excellent pharmacokinetics in rats and robust efficacy in hamsters. Compared to anacetrapib, the compound showed substantially reduced lipophilicity, had only modest distribution into adipose tissue, and retained potency in hypertriglyceridemic plasma in vitro and in vivo. Furthermore, in contrast to torcetrapib, the compound did not increase aldosterone secretion in human adrenocortical carcinoma cells nor in chronically cannulated rats. On the basis of its preclin. efficacy and safety profile, the compound was advanced into clin. trials.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 324769-07-5 belongs to class piperidines, name is 1-N-Boc-2-Ethylpiperidin-4-one, and the molecular formula is C12H21NO3, Application of 1-N-Boc-2-Ethylpiperidin-4-one.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Teng, Mingxing published the artcileDevelopment of CDK2 and CDK5 Dual Degrader TMX-2172, Quality Control of 73874-95-0, the main research area is ovarian cancer CDK2 CDK5 dual degrader antiproliferative CCNE1; CDK2; CDK5; cancer; cell cycle; drug design; protein degradation.

Cyclin-dependent kinase 2 (CDK2) is a potential therapeutic target for the treatment of cancer. Development of CDK2 inhibitors has been extremely challenging as its ATP-binding site shares high similarity with CDK1, a related kinase whose inhibition causes toxic effects. Here, we report the development of TMX-2172(I), a heterobifunctional CDK2 degrader with degradation selectivity for CDK2 and CDK5 over not only CDK1, but transcriptional CDKs (CDK7 and CDK9) and cell cycle CDKs (CDK4 and CDK6) as well. In addition, we demonstrate that antiproliferative activity in ovarian cancer cells (OVCAR8) depends on CDK2 degradation and correlates with high expression of cyclin E1 (CCNE1), which functions as a regulatory subunit of CDK2. Collectively, our work provides evidence that TMX-2172 represents a lead for further development and that CDK2 degradation is a potentially valuable therapeutic strategy in ovarian and other cancers that overexpress CCNE1.

Angewandte Chemie, International Edition published new progress about Antitumor agents. 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

Li, Wen-Zhen published the artcileDesign, synthesis, and biological evaluation of benzo[b]thiophene 1,1-dioxide derivatives as potent STAT3 inhibitors, Related Products of piperidines, the main research area is benzothiophene dioxide STAT3 inhibitor structure activity relationship; anticancer activity benzothiophene mol modeling; ROS; STAT3; apoptosis; cell cycle; inhibitors; mitochondrial membrane potential; tumors.

As a member of the signal transducer and activator of transcription (STAT) family, STAT3 plays a critical role in several biol. pathways such as cell proliferation, migration, survival, and differentiation. Due to abnormal continuous activation in tumors, inhibition of STAT3 has emerged as an attractive approach for the treatment of various cancer cells. Herein, we report a series of novel STAT3 inhibitors based on benzo[b]thiophene 1,1-dioxide scaffold and evaluated their anticancer potency. Among them, compound I exhibited the best activity against cancer cells. Compound I induced apoptosis and blocked the cell cycle. Meanwhile, I reduced intracellular ROS content and caused the loss of mitochondrial membrane potential. Further research revealed that I significantly blocked STAT3 phosphorylation and STAT3-dependent dual-luciferase reporter gene experiments showed that compound I has a marked inhibition of STAT3-mediated Firefly luciferase activity. Mol. modeling studies revealed compound I occupied the pocket well with the SH2 domain in a favorable conformation.

Chemical Biology & Drug Design published new progress about Antitumor agents. 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

Zhou, Zhe published the artcileTargeted degradation of CD147 proteins in melanoma, Safety of tert-Butyl piperidin-4-ylcarbamate, the main research area is CD147 PROTAC pseudolaric acid B derivative; CD147; Degradation; Melanoma; PROTAC; Pseudolaric Acid B.

CD147 is a transmembrane glycoprotein and a member of Ig superfamily, is strongly expressed in melanoma cells. CD147 has a pivotal role in tumor development. Therefore, it is a potential drug target for melanoma. In this article, we report the discovery of the first CD147 protein proteolysis targeting chimeras (PROTACs) derived from the natural product pseudolaric acid B (PAB). The representative compound 6a (I) effectively induced degradation of CD147 and inhibited melanoma cells in vitro and in vivo. 6A could be used as the novel type of anticancer agent or as a part of the mol. biol. research toolkit used in the gain-of-function study of the dynamic roles of CD147 in cancer networks.

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

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Yu, Jiang published the artcileStructure-based design, synthesis, and evaluation of inhibitors with high selectivity for PARP-1 over PARP-2, Quality Control of 73874-95-0, the main research area is azepino indolone design synthesis mol docking anticancer PARP selectivity; Cancer; PARP-1 inhibitor; Rucaparib analogues; Selectivity; Structure based design.

The poly (ADP-ribose) polymerase (PARP) inhibitors play a crucial role in cancer therapy. However, most approved PARP inhibitors have lower selectivity to PARP-1 than to PARP-2, so they will inevitably have side effects. Based on the different catalytic domains of PARP-1 and PARP-2, we developed a strategy to design and synthesize highly selective PARP-1 inhibitors. A few selected compounds (labeled Y17, Y29, Y31 and Y49) showed excellent PARP-1 inhibition, and their IC50 values were 0.61, 0.66, 0.41 and 0.96 nM, resp. Then, Y49 (PARP-1 IC50 = 0.96 nM, PARP-2 IC50 = 61.90 nM, selectivity PARP-2/PARP-1 = 64.5) was proved to be the most selective inhibitor of PARP-1. Compounds Y29 and Y49 showed stronger inhibitory effect on proliferation in BRCA1 mutant MX-1 cells than in other cancer cells. In the MDA-MB-436 xenotransplantation model, Y49 was well tolerated and showed remarkable single dose activity. The design strategy proposed in this paper is of far-reaching significance for the further construction of the next generation of selective PARP-1 inhibitors.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 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

Pan, Chenghao published the artcileDesign, synthesis and biological evaluation of quinazoline derivatives as potent and selective FGFR4 inhibitors, SDS of cas: 73874-95-0, the main research area is hepatocellular carcinoma FGFR4 inhibitor quinazoline derivative anticancer; FGFR4 inhibitors; Hepatocellular carcinoma (HCC); Solvent region modification.

Aberrant activation of the fibroblast growth factor 19-fibroblast growth factor receptor 4 (FGF19-FGFR4) signaling pathway has been proved to promote hepatocellular carcinoma (HCC) proliferation. It is assumed that the first FGFR4 inhibitor BLU9931 did not enter clin. studies, presumably due to its rapid metabolism in liver microsomes. Here, we report the development of series of quinazoline derivatives based on FGFR4 inhibitor BLU9931 through structural modification of its solvent region pocket to minimize its potential metabolic liability. Among them, compound 35a exhibited comparable or superior kinase inhibitory activity (IC50 = 8.5 nM) and selectivity in cells. More importantly, compound 35a improved liver microsomes stability compared to BLU9931. Cellular mechanistic studies demonstrated that 35a induced apoptosis via the FGFR4 signaling pathway blockage. In addition, the computational simulation revealed the possible binding mode to FGFR4 protein, which provides a plausible explanation of high potent and metabolic stability.

European Journal of Medicinal Chemistry published new progress about Antitumor 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

Liu, Yang published the artcileExtensive investigation of benzylic N-containing substituents on the pyrrolopyrimidine skeleton as Akt inhibitors with potent anticancer activity, Application In Synthesis of 73874-95-0, the main research area is anticancer Akt docking mantle cell lymphoma cytotoxicities antiproliferative; Akt; Anticancer; Docking; Mantle cell lymphoma; Pyrrolopyrimidines.

Continuous optimization of benzylic substituents on 1-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl)-2-phenylethan-1-one structure as Akt inhibitors was described in this paper. Particularly, compounds 8 and 14g exhibited high enzymic potency against all Akt isoforms and antiproliferative effects in mantle cell lymphoma cell lines, as well as favorable cytotoxicities in patient primary cancer cells. Low micromolar doses of both 8 and 14g dose-dependently induced cell apoptosis and G2/M cell cycle arrest, also suppressed the phosphorylation level of Akt downstream targets GSK3β and S6.

Bioorganic Chemistry published new progress about Antitumor 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

Zhao, Min published the artcileSynthesis and evaluation of new compounds bearing 3-(4-aminopiperidin-1-yl)methyl magnolol scaffold as anticancer agents for the treatment of non-small cell lung cancer via targeting autophagy, COA of Formula: C10H20N2O2, the main research area is magnolol aminopiperidinylmethyl preparation anticancer non small cell lung cancer; Autophagy; Magnolia officinalis; Magonolol; Non-small cell lung cancer.

Magnolol and honokiol are the two major active ingredients with similar structure and anticancer activity from traditional Chinese medicine Magnolia officinalis, and honokiol is now in a phase I clin. trial (CTR20170822) for advanced non-small cell lung cancer (NSCLC). In search of potent lead compounds with better activity, our previous study has demonstrated that magnolol derivative 3-(4-aminopiperidin-1-yl)methyl magnolol has better activity than honokiol. Here, based on the core of 3-(4-aminopiperidin-1-yl)methyl magnolol, we synthesized fifty-one magnolol derivatives Among them, compound I exhibited the most potent antiproliferative activities on H460, HCC827, H1975 cell lines with the IC50 values of 0.63-0.93μM, which were approx. 10- and 100-fold more potent than those of C2 and magnolol, resp. Besides, oral administration of I and C2 on an H460 xenograft model also demonstrated that I has better activity than C2. Mechanism study revealed that I induced G0/G1 phase cell cycle arrest, apoptosis and autophagy in cancer cells. Moreover, blocking autophagy by the autophagic inhibitor enhanced the anticancer activity of I in vitro and in vivo, suggesting autophagy played a cytoprotective role on I-induced cancer cell death. Taken together, our study implied that compound I combined with autophagic inhibitor could be another choice for NSCLC treatment in further investigation.

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

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Crider, A. Michael published the artcileSynthesis of nitrosourea derivatives of pyridine and piperidine as potential anticancer agents, HPLC of Formula: 1205-72-7, the main research area is nitrosourea piperidinyl chloroethyl; anticancer piperidinylnitrosourea.

RNHCON(NO)CH2CH2Cl (I; R = 1-benzyl-3-piperidinyl, 1-benzyl-4-piperidinyl, 1-butyl-4-piperidinyl, 1-ethyl-3-piperidinyl, 3-pyridyl) were prepared (by reaction of RNH2 with ClCH2CH2NCO followed by nitrosation of RNHCONHCH2CH2Cl) and evaluated for anticancer activity. I (R = 1-benzyl-4-piperidinyl) hydrogen maleate exhibited good activity against intracranial L1210 leukemia as well as the mouse ependymoblastoma brain tumor system. It exhibited comparable activity in the Lewis lung carcinoma system to N,N’-bis(2-chloroethyl)-N-nitrosourea. Replacement of the N-benzyl group in both the 3-piperidinyl- and 4-piperidinylnitrosoureas resulted in less active compounds in all tumor systems tested. I (R = 3-pyridyl) was inactive in the L-1210 leukemia system.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 1205-72-7 belongs to class piperidines, name is 1-Benzylpiperidin-4-amine dihydrochloride, and the molecular formula is C12H20Cl2N2, HPLC of Formula: 1205-72-7.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem