Month: November 2022

Motika, Stephen E. published the artcileGram-Negative Antibiotic Active Through Inhibition of an Essential Riboswitch, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is antibiotic riboswitch ribocil.

Multidrug-resistant Gram-neg. (GN) infections for which there are few available treatment options are increasingly common. The development of new antibiotics for these pathogens is challenging because of the inability of most small mols. to accumulate inside GN bacteria. Using recently developed predictive guidelines for compound accumulation in Escherichia coli, we have converted the antibiotic Ribocil C, which targets the FMN (FMN) riboswitch, from a compound lacking whole-cell activity against wild-type GN pathogens into a compound that accumulates to a high level in E. coli, is effective against Gram-neg. clin. isolates, and has efficacy in mouse models of GN infections. This compound allows for the first assessment of the translational potential of FMN riboswitch binders against wild-type Gram-neg. bacteria.

Journal of the American Chemical Society published new progress about Acinetobacter baumannii. 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

Koskinen, Ari published the artcileNovel applications of the modified Polonovski reaction. III. Regiospecific functionalization of carbon atoms α to heterocyclic nitrogen, Recommanded Product: Methyl 1-methylpiperidine-2-carboxylate, the main research area is Polonovski reaction piperidine carboxylate; nitrile piperidine.

A nitrile substituent was introduced at the exocyclic α C atom of the piperidine N, making the center either nucleo- or electrophilic in subsequent transformations. Piperidineacetates I (R1 = Me, Et, Ph, R2 = R3 = H; R1 = R2 = Me, R3 = H; R1 = Me, R2 = H, R3 = Et, Δ3) and II (R4 = CO2Me) were oxidized and the product converted via a modified Polonovski reaction [(F3CCO)2O instead of Ac2O] to the cyano compounds III and II (R4 = cyano), as well as IV and V (R4 = cyano). The generality of the method, along with the ease of operation, high yields, and regiospecificity, make this reaction highly versatile for synthetic purposes.

Tetrahedron published new progress about Polonovski fragmentation. 1690-74-0 belongs to class piperidines, name is Methyl 1-methylpiperidine-2-carboxylate, and the molecular formula is C8H15NO2, Recommanded Product: Methyl 1-methylpiperidine-2-carboxylate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Bu, Hong published the artcileDesign, synthesis and biological evaluation of imidazopyridazine derivatives containing isoquinoline group as potent MNK1/2 inhibitors, Product Details of C10H20N2O2, the main research area is eIF4E MNK inhibitor ETC 206; ETC-206; MNK1/2 kinases; MNKs inhibitor; eIF4E.

Mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are located at the meeting-point of ERK and p38 MAPK signaling pathways, which can phosphorylate eukaryotic translation initiation factor 4E (eIF4E) at the conserved serine 209 exclusively. MNKs modulate the translation of mRNA involved in tumor-associated signaling pathways. Consequently, selective inhibitors of MNK1/2 could reduce the level of phosphorylated eIF4E. Series of imidazopyrazines, imidazopyridazines and imidazopyridines derivatives were synthesized and evaluated as MNK1/2 inhibitors. Several compounds exhibited great inhibitory activity against MNK1/2 and selected compounds showed moderate to excellent anti-proliferative potency against diffuse large B-cell lymphoma (DLBCL) cell lines. In particular, compound II-5 (MNK1 IC50 = 2.3 nM; MNK2 IC50 = 3.4 nM) exhibited excellent enzymic inhibitory potency and proved to be the most potent compound against TMD-8 and DOHH-2 cell lines with IC50 value of 0.3896μM and 0.4092μM resp. These results demonstrated that compound II-5 could be considered as a potential MNK1/2 inhibitor for further investigation.

Bioorganic & Medicinal Chemistry published new progress about Antiproliferative 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

Wang, Xinran published the artcileDesign, synthesis and biological evaluation of 2-aminopyrimidine-based LSD1 inhibitors, HPLC of Formula: 73874-95-0, the main research area is human liver microsome cell proliferation LSD1 inhibitor; 2-Aminopyrimidine; LSD1 inhibitors; Molecular docking; Structure-activity relationships.

AZD9291, with excellent pharmaceutical properties, has been reported to have certain LSD1 inhibitory activity. Therefore, we carried out structural optimization based on the AZD9291 skeleton to increase the LSD1 inhibitory potential of the compound Then, a series of 2-aminopyrimidine derivatives were designed and synthesized as LSD1 inhibitors, and their structure-activity relationships were studied. The most promising compound, X43, with an IC50 of 0.89 μM showed remarkable LSD1 selectivity not only to EGFRwt (>100-fold) but also to MAO-A/B (>50-fold). Further studies showed that X43 inhibited LSD1 activity and induced the apoptosis of A549 cells in a dose-dependent manner. Meanwhile, compound X43 showed a superior ability to inhibit the proliferation of A549 and THP-1 cells, with IC50 values of 1.62 μM and 1.21 μM, resp. Then, analyses of the stability of human liver microsomes, CYP inhibition and in vivo pharmacokinetics in rats showed that X43 had favorable profiles in vitro and in vivo and the potential for further study. Our findings suggested that a 2-aminopyrimidine-based LSD1 inhibitor deserves further investigation as a treatment for LSD1-overexpressing cancer.

Bioorganic Chemistry published new progress about Antiproliferative agents. 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

Yuan, Xinrui published the artcileDesign, synthesis and biological evaluation of pyridone-aminal derivatives as MNK1/2 inhibitors, Quality Control of 73874-95-0, the main research area is pyridone aminal derivative preparation MNK1 MNK2 inhibitor colon cancer; MNK1/2; Pyridone–aminal; eFT508; eIF4E.

Excessive phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) plays a major role in the dysregulation of mRNA translation and the activation of tumor cell signaling. eIF4E is exclusively phosphorylated by mitogen-activated protein kinase interacting kinases 1 and 2 (MNK1/2) on Ser209. So, MNK1/2 inhibitors could decrease the level of p-eIF4E and regulate tumor-associated signaling pathways. A series of pyridone-aminal derivatives were synthesized and evaluated as MNK1/2 inhibitors. Several compounds exhibited great inhibitory activity against MNK1/2 and selected compounds showed moderate to excellent anti-proliferative potency against hematol. cancer cell lines. In particular, compound 42i (MNK1 IC50 = 7.0 nM; MNK2 IC50 = 6.1 nM) proved to be the most potent compound against TMD-8 cell line with IC50 value of 0.91 μM. Furthermore, 42i could block the phosphorylation level of eIF4E in CT-26 cell line, and 42i inhibited the tumor growth of CT-26 allograft model significantly. These results indicated that compound 42i was a promising MNK1/2 inhibitor for the potent treatment of colon cancer.

Bioorganic & Medicinal Chemistry published new progress about Antiproliferative 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

Winter-Holt, Jon J. published the artcileDiscovery of a Potent and Selective ATAD2 Bromodomain Inhibitor with Antiproliferative Activity in Breast Cancer Models, Safety of tert-Butyl piperidin-4-ylcarbamate, the main research area is ATAD2 bromodomain inhibitor antiproliferative breast cancer.

ATAD2 is an epigenetic bromodomain-containing target which is overexpressed in many cancers and has been suggested as a potential oncol. target. While several small mol. inhibitors have been described in the literature, their cellular activity has proved to be underwhelming. In this work, we describe the identification of a novel series of ATAD2 inhibitors by high throughput screening, confirmation of the bromodomain region as the site of action, and the optimization campaign undertaken to improve the potency, selectivity, and permeability of the initial hit. The result is compound 5 (AZ13824374)(I), a highly potent and selective ATAD2 inhibitor which shows cellular target engagement and antiproliferative activity in a range of breast cancer models.

Journal of Medicinal Chemistry published new progress about Antiproliferative 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

Buravchenko, Galina I. published the artcileSynthesis of 7-amino-6-halogeno-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides: a way forward for targeting hypoxia and drug resistance of cancer cells, Product Details of C10H20N2O2, the main research area is aminohalogeno phenylquinoxaline carbonitriledioxide hypoxia cancer drug resistance.

To establish a new approach for the synthesis of quinoxaline 1,4-dioxides as hypoxia-selective cytotoxic agents, an original multi-step preparation of derivatives possessing the diamine moiety at position 7 was evaluated. Herein, we present the synthesis of a series of novel 7-amino-6-halogeno-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides 13a-h, 14a,b,g based on the regioselective Beirut reaction. Comparison of antitumor properties of derivatives possessing the diamine moiety at position 7 with structurally close congeners possessing the corresponding amino groups at position 6 revealed key differences in the cytotoxicity profiles and HIF-1α inhibition. All the synthesized 7-amino-6-halogeno derivatives 13a-h, 14a,b,g demonstrated significant cytotoxic activities against breast cancer cell lines (MCF7, MDA-MB-231) in normoxia and hypoxia with IC50 values ranging from 0.1 to 7.6 μM. Most of these novel derivatives can circumvent the multidrug resistance of tumor cells caused by P-glycoprotein over expression. The lead compounds 13a, 14a and 14b can suppress the expression of HIF-1α at low micromolar concentrations and induce apoptosis in breast cancer MCF7 cells. In addition, compound 14b effectively inhibits BCL2 and ERα expression in MCF7 cells. The current research opens a new direction for targeting hypoxia and drug resistance of cancer cells.

RSC Advances published new progress about Antiproliferative 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

Oum, Yoon Hyeun published the artcileDiscovery of novel aminopiperidinyl amide CXCR4 modulators through virtual screening and rational drug design, Application In Synthesis of 73874-95-0, the main research area is antiinflammatory CXCR4 chemokine modulator ligand shape similarity docking MDS; C-X-C chemokine receptor type 4 (CXCR4); Chemokine modulator; Ligand shape similarity; Molecular docking; Molecular dynamics; Structure-based drug design.

The C-X-C chemokine receptor type 4 (CXCR4) is a potential therapeutic target for HIV infection, metastatic cancer, and inflammatory autoimmune diseases. In this study, we screened the ZINC chem. database for novel CXCR4 modulators through a series of in silico guided processes. After evaluating the screened compounds for their binding affinities to CXCR4 and inhibitory activities against the chemoattractant CXCL12, we identified a hit compound (ZINC 72372983) showing 100 nM affinity and 69% chemotaxis inhibition at the same concentration (100 nM). To increase the potency of our hit compound, we explored the protein-ligand interactions at an at. level using mol. dynamics simulation which enabled us to design and synthesize a novel compound (Z7R) with nanomolar affinity (IC50 = 1.25 nM) and improved chemotaxis inhibition (78.5%). Z7R displays promising anti-inflammatory activity (50%) in a mouse edema model by blocking CXCR4-expressed leukocytes, being supported by our immunohistochem. study.

European Journal of Medicinal Chemistry published new progress about Anti-inflammatory 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

Liu, Xuwen published the artcileSynthesis and structure-activity relationships of thieno[2,3-d]pyrimidines as atypical protein kinase C inhibitors to control retinal vascular permeability and cytokine-induced edema, COA of Formula: C10H20N2O2, the main research area is structure preparation thieno pyrimidine derivative aPKC retinal vascular permeability; Blinding eye diseases; Homology model; SAR; Thieno[2,3-d]pyrimidine inhibitors; Tumor necrosis factor-α (TNFα); Vascular endothelial growth factor (VEGF); Vascular permeability; atypical protein kinase C (aPKC).

Studies demonstrate that small mol. targeting of atypical protein kinase C (aPKC) may provide an effective means to control vascular permeability, prevent edema, and reduce inflammation providing novel and important alternatives to anti-VEGF therapies for certain blinding eye diseases. Based on a literature tricyclic thieno[2,3-d]pyrimidine lead (1), an ATP-competitive inhibitor of the aPKC iota (ι) and aPKC zeta (ζ) isoforms, we have synthesized a small series of compounds in 1-2 steps from a readily available chloro intermediate. A single pyridine congener was also made using 2D NMR to assign regiochem. Within the parent pyrimidine series, a range of potencies was observed against aPKCζ whereas the pyridine congener was inactive. Selected compounds were also tested for their effect toward VEGF-induced permeability in BREC cells. The most potent of these (7l) was further assayed against the aPKCι isoform and showed a favorable selectivity profile against a panel of 31 kinases, including kinases from the AGC superfamily, with a focus on PKC isoforms and kinases previously shown to affect permeability. Further testing of 7l in a luciferase assay in HEK293 cells showed an ability to prevent TNF-α induced NFκB activation while not having any effect on cell survival. Intravitreal administration of 7l to the eye yielded a complete reduction in permeability in a test to determine whether the compound could block VEGF- and TNFα-induced permeability across the retinal vasculature in a rat model. The compound in mice displayed good microsomal stability and in plasma moderate exposure (AUC and Cmax), low clearance, a long half-life and high oral bioavailability. With IV dosing, higher levels were observed in the brain and eye relative to plasma, with highest levels in the eye by either IV or PO dosing. With a slow oral absorption profile, 7l accumulates in the eye to maintain a high concentration after dosing with higher levels than in plasma. Compound 7l may represent a class of aPKC inhibitors for further investigation.

Bioorganic & Medicinal Chemistry published new progress about Anti-inflammatory 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

Rabal, Obdulia published the artcileDesign and Synthesis of Novel Epigenetic Inhibitors Targeting Histone Deacetylases, DNA Methyltransferase 1, and Lysine Methyltransferase G9a with In Vivo Efficacy in Multiple Myeloma, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is histone deacetylases DNA methyltransferase G9a inhibitors multiple myeloma antitumor.

Concomitant inhibition of key epigenetic pathways involved in silencing tumor suppressor genes has been recognized as a promising strategy for cancer therapy. Herein, we report a first-in-class series of quinoline-based analogs that simultaneously inhibit histone deacetylases (from a low nanomolar range) and DNA methyltransferase-1 (from a mid-nanomolar range, IC50 < 200 nM). Addnl., lysine methyltransferase G9a inhibitory activity is achieved (from a low nanomolar range) by introduction of a key lysine mimic group at the 7-position of the quinoline ring. The corresponding epigenetic functional cellular responses are observed: histone-3 acetylation, DNA hypomethylation, and decreased histone-3 methylation at lysine-9. These chem. probes, multi-target epigenetic inhibitors, were validated against the multiple myeloma cell line MM1.S, demonstrating promising in vitro activity of 12a (CM-444) with GI50 of 32 nM, an adequate therapeutic window (>1 log unit), and a suitable pharmacokinetic profile. In vivo, 12a achieved significant antitumor efficacy in a xenograft mouse model of human multiple myeloma.

Journal of Medicinal Chemistry published new progress about Acetylation (histone H3). 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