Category: piperidines

Rubach, Jon K. published the artcileThe Amino-Acid Substituents of Dipeptide Substrates of Cathepsin C Can Determine the Rate-Limiting Steps of Catalysis, Safety of 1-((9H-Fluoren-9-yl)methyl)piperidine, the publication is Biochemistry (2012), 51(38), 7551-7568, database is CAplus and MEDLINE.

We examined the cathepsin C-catalyzed hydrolysis of dipeptide substrates of the form Yaa-Xaa-AMC, using steady-state and pre-steady-state kinetic methods. The substrates group into three kinetic profiles based upon the broad range observed for k_cat/K_a and k_cat values, pre-steady-state time courses, and solvent kinetic isotope effects (sKIEs). The dipeptide substrate Gly-Arg-AMC displayed large values for k_cat/K_a (1.6±0.09 μM^-1 s^-1) and k_cat (255±6 s^-1), an inverse sKIE on k_cat/K_a (^D(k_cat/K_a) = 0.6±0.15), a modest, normal sKIE on k_cat (^Dk_cat = 1.6±0.2), and immeasurable pre-steady-state kinetics, indicating an extremely fast pre-steady-state rate (>400 s^-1). (Errors on fitted values are omitted in the text for clarity but may be found in Table 2.). These results conformed to a kinetic model where the acylation (k_ac) and deacylation (k_dac) half-reactions are very fast and similar in value. The second substrate type, Gly-Tyr-AMC and Ser-Tyr-AMC, the latter the subject of a comprehensive kinetic study (Schneck et al. (2008) Biochem. 47, 8697-8710), were found to be less active substrates compared to Gly-Arg-AMC, with resp. k_cat/K_a values of 0.49±0.07 μM^-1 s^-1 and 5.3±0.5 μM^-1 s^-1, and k_cat values of 28±1 s^-1 and 25±0.5 s^-1. Solvent kinetic isotope effects for Ser-Tyr-AMC were found to be inverse for k_cat/K_a (^D(k_cat/K_a) = 0.74±0.05) and normal for k_cat (^Dk_cat = 2.3±0.1) but unlike Gly-Arg-AMC, pre-steady-state kinetics of Gly-Tyr-AMC and Ser-Tyr-AMC were measurable and characterized by a single-exponential burst, with fast transient rates (490 s^-1 and 390 s^-1, resp.), from which it was determined that k_ac ≫ k_dac ∼ k_cat. The third substrate type, Gly-Ile-AMC, gave very low values of k_cat/K_a (0.0015±0.0001 μM^-1 s^-1) and k_cat (0.33±0.02 s^-1), no sKIEs, (^D(k_cat/K_a) = 1.05±0.5 and ^Dk_cat = 1.06±0.4), and pre-steady-state kinetics exhibited a discernible, but negligible, transient phase. For this third class of substrate, kinetic modeling was consistent with a mechanism in which k_dac > k_ac ∼ k_cat, and for which an isotope-insensitive step in the acylation half-reaction is the slowest. The combined results of these studies suggested that the identity of the amino acid at the P₁ position of the substrate is the main determinant of catalysis. On the basis of these kinetic data, together with crystallog. studies of substrate analogs and mol. dynamics anal. with models of acyl-enzyme intermediates, we present a catalytic model derived from the relative rates of the acylation vs. deacylation half-reactions of cathepsin C. The chem. steps of catalysis are proposed to be dependent upon the conformational freedom of the amino acid substituents for optimal alignment for thiolation (acylation) or hydrolysis (deacylation). These studies suggest ideas for inhibitor design for papain-family cysteine proteases and strategies to progress drug discovery for other classes of disease-relevant cysteine proteases.

Biochemistry published new progress about 35661-58-6. 35661-58-6 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-((9H-Fluoren-9-yl)methyl)piperidine, and the molecular formula is C19H21N, Safety of 1-((9H-Fluoren-9-yl)methyl)piperidine.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Ye, Jian published the artcileInvestigation of catalytic self-cleaning process of multiple active species decorated macroporous PVDF membranes through peroxymonosulfate activation, Computed Properties of 826-36-8, the publication is Journal of Colloid and Interface Science (2021), 178-189, database is CAplus and MEDLINE.

Currently, carbon-based catalysts integrated with macroporous catalytic membrane have aroused considerable attention for environmental remediation because of its practicability and high efficiency. Herein, nitrogen doped carbon nanotube hybrids (Fe-Co@NC-CNTs) decorated with multiple active species (Fe₃Co₇/CoFe₂O₄@Fe/Co-N-C) were designed through N-mol. assisted pyrolysis of bimetallic (Fe/Co) metal-organic frameworks, and then immobilized on poly(vinylidene fluoride) (PVDF) membrane to construct macroporous Fe-Co@NC-CNTs/PVDF catalytic membrane via directional freezing technique, where active sites were efficiently exposed for oxidants and target pollutants. As expected, Fe-Co@NC-CNTs/PVDF membrane successfully achieved almost 100% bisphenol A (BPA) degradation after 40 min via PMS activation, which was significantly overperformed the majority of conventional carbon-based catalysts. Besides, we found that Fe-Co@NC-CNTs/PVDF membrane not only exhibited ideal catalytic and self-cleaning property in humic acid (HA)-BPA coexistence system, but also maintained the excellent reusability and ultrahigh water flux (10464.45 L m^-2 h^-1) even after 5 cycles. Notably, in EPR anal. and quenching experiments, it was found that sulfate radicals (SO₄·^– and ·OH) and singlet oxygen (¹O₂) participated the degradation process while ¹O₂ made a major contribution. More significantly, this study is very meaningful for the development of novel catalytic self-cleaning membranes with PMS activation.

Journal of Colloid and Interface Science published new progress about 826-36-8. 826-36-8 belongs to piperidines, auxiliary class Natural product, name is 2,2,6,6-Tetramethylpiperidin-4-one, and the molecular formula is C10H16Br3N, Computed Properties of 826-36-8.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Crich, David published the artcileInfluence of the 4,6-O-benzylidene, 4,6-O-phenylboronate, and 4,6-O-polystyrylboronate protecting groups on the stereochemical outcome of thioglycoside-based glycosylations mediated by 1-benzenesulfinyl piperidine/triflic anhydride and N-iodosuccinimide/trimethylsilyl triflate, Category: piperidines, the publication is Journal of Organic Chemistry (2003), 68(21), 8142-8148, database is CAplus and MEDLINE.

The effect of 4,6-O-benzylidene acetals, 4,6-O-phenylboronate esters, and 4,6-O-polystyrylboronate esters on the stereoselectivity of couplings to galacto-, gluco-, and mannopyranosyl thioglycosides, otherwise protected with benzyl ethers, has been investigated by the benzenesulfinyl piperidine/trifluoromethanesulfonic anhydride (BSP), di-Ph sulfoxide/trifluoromethanesulfonic anhydride (Ph₂SO), and N-iodosuccinimide/trimethylsilyl trifluoromethanesulfonate (NIS/TMSOTf) methods. The BSP and Ph₂SO methods give comparable results in all three systems whereas the NIS method affords significantly different stereoselectivities in both the gluco and manno, but not the galacto series. The benzylidene acetal and boronate esters influence the stereochem. in a similar manner in the β-selective manno series and the α-selective galacto series but show significant differences with the glucose donors. The differences between the glucose, galactose, and mannose series reflect the established differences in reactivity and, especially for mannose, those in the anomeric effect and are best interpreted in terms of changes in the relative energetics between the α- and β-covalent triflate intermediates and the various contact ion pairs with which they are necessarily in equilibrium

Journal of Organic Chemistry published new progress about 4972-31-0. 4972-31-0 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-(Phenylsulfinyl)piperidine, and the molecular formula is C11H15NOS, Category: piperidines.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Crich, David published the artcileSynthesis of the mannosyl erythritol lipid MEL A; confirmation of the configuration of the meso-erythritol moiety, Application In Synthesis of 4972-31-0, the publication is Tetrahedron (2002), 58(1), 35-44, database is CAplus.

The total synthesis of the two possible diastereomers of mannosylerythritol lipid A, a novel biosurfactant from Candida antarctica T-34 with promising anti-proliferative properties in several cell lines, is described. By comparison with an authentic sample, the natural material is confirmed as a single diastereomer with the 4-O-(β-D-mannopyranosyl)-D-erythritol configuration.

Tetrahedron published new progress about 4972-31-0. 4972-31-0 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-(Phenylsulfinyl)piperidine, and the molecular formula is C11H15NOS, Application In Synthesis of 4972-31-0.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Sugasawa, Shigehiko published the artcileSynthesis of piperidine derivatives, Safety of (1-Methylpiperidin-3-yl)methanamine, the publication is Yakugaku Zasshi (1956), 968-70, database is CAplus.

4-MeO₂CC₅H₄N (60 g.) and 60 ml. 28% NH₄OH at 0° saturated with NH₃ gas, kept overnight and the product recrystallized from EtOH gave 44.2 g. 4-H₂NOCC₅H₄N (I), m. 152-5°. I or 3-H₂NCOC₅H₄N (10 g.), 17.5 g. MeI, and 30 ml. MeOH refluxed 5 hrs., the MeI and MeOH removed in vacuo, the residue in 30 ml. water converted to its acid chloride by usual method, reduced with PtO₂ and H until absorption of 3 moles H, and the product concentrated and recrystallized from EtOH yielded about 85% 1,x-Me(H₂NOC)C₅H₉N.HCl (II, x = 3, m. 232°; x = 4, hygroscopic). II (7 g.) and 7 g. P₂O₅ heated 3 hrs. at 160-80°, cooled, 50 ml. water added, neutralized with K₂CO₃ and the product extracted with AcOEt yielded about 80% 1,x-Me(NC)C₅H₉N (III, x = 3, b₂₀ 95-6°; x = 4, b₂₁ 97°). LiAlH₄ (1.3 g.) and 150 ml. Et₂O at 0° treated dropwise with 5 g. III in 50 ml. Et₂O, stirred 1.5 hrs., refluxed 30 min., cooled, 15 ml. water added, the precipitate filtered off, treated with 50 ml. 20% Rochelle salt solution, extracted with Et₂O, the Et₂O layer and the Et₂O extract combined and distilled yielded about 90% 1,x-Me(H₂NCH₂)C₅H₉N {IV, x = 3, b₂₀ 81-2° [dipicrate, m. 231° (decomposition)]; x = 4, b₂₀ 80-1° [dipicrate, m. 236° (decomposition)]}. KOH (32 g.) in 400 ml. water treated with 6.4 g. Br, the solution at 0° treated with 5.7 g. II in a small amount of water, heated 1 hr. at 70°, made strongly alk. with KOH, the product steam distilled into dilute HCl, the solution concentrated, made alk. with KOH and extracted with Et₂O yielded about 65% 1,x-Me(H₂N)C₅H₉N {V, x = 3, b₄₃ 74-5° [dipicrate, m. 277° (decomposition)]; x = 4, b₃₅, 70-1° [dipicrate, m. 263° (decomposition)]}. R₂NH (0.6 mole) in 200 ml. PhMe poured dropwise into 50% COCl₂, refluxed 1 hr. and the product distd, yielded 71% R₂NCOCl (VI, R = Me, b_55-60 85-8°; R = Et, b_17-20 80°). IV or V (2 moles) and 1 mole VI in Et₂O mixed at 0°, let stand 1.5 hrs. at room temperature, refluxed 10 min., the solution filtered and the filtrate concd, gave 1,x-Me[R₂NCONH(CH₂)_n]C₅H₉N (x, n, R, and m.p. given): 4, 1, Me, 40-4° [HCl salt, 230° (decomposition)]; 4, 1, Et, 66-8°; 4, 0, Me, 138-9°; 4, 0, Et, 89-90°; 3, 1, Me, 66-9°; 3, 1, Et, -(sirup); 3, 0, Me, 110-2°; 3, 0, Et, -(sirup) (picrolonate, m. 195-7°).

Yakugaku Zasshi published new progress about 14613-37-7. 14613-37-7 belongs to piperidines, auxiliary class Piperidine,Amine, name is (1-Methylpiperidin-3-yl)methanamine, and the molecular formula is C17H16O2, Safety of (1-Methylpiperidin-3-yl)methanamine.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Johannes, Jeffrey W. published the artcileStructure-Based Design of Selective Noncovalent CDK12 Inhibitors, Safety of (R,E)-N-(4-(3-((5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidine-1-carbonyl)phenyl)-4-(dimethylamino)but-2-enamide, the publication is ChemMedChem (2018), 13(3), 231-235, database is CAplus and MEDLINE.

Cyclin-dependent kinase (CDK) 12 knockdown via siRNA decreases the transcription of DNA-damage-response genes and sensitizes BRCA wild-type cells to poly(ADP-ribose) polymerase (PARP) inhibition. To recapitulate this effect with a small mol., we sought a potent, selective CDK12 inhibitor. Crystal structures and modeling informed hybridization between dinaciclib and SR-3029, resulting in lead compound 5 [(S)-2-(1-(6-(((6,7-difluoro-1H-benzo[d]imidazol-2-yl)methyl)amino)-9-ethyl-9H-purin-2-yl)piperidin-2-yl)ethan-1-ol]. Further structure-guided optimization delivered a series of selective CDK12 inhibitors, including compound 7 [(S)-2-(1-(6-(((6,7-difluoro-1H-benzo[d]imidazol-2-yl)methyl)amino)-9-isopropyl-9H-purin-2-yl)piperidin-2-yl)ethan-1-ol]. Profiling of this compound across CDK9, 7, 2, and 1 at high ATP concentration, single-point kinase panel screening against 352 targets at 0.1 μM, and proteomics via kinase affinity matrix technol. demonstrated the selectivity. This series of compounds inhibits phosphorylation of Ser2 on the C-terminal repeat domain of RNA polymerase II, consistent with CDK12 inhibition. These selective compounds were also acutely toxic to OV90 as well as THP1 cells.

ChemMedChem published new progress about 1702809-17-3. 1702809-17-3 belongs to piperidines, auxiliary class Cell Cycle,CDK, name is (R,E)-N-(4-(3-((5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidine-1-carbonyl)phenyl)-4-(dimethylamino)but-2-enamide, and the molecular formula is C30H32ClN7O2, Safety of (R,E)-N-(4-(3-((5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidine-1-carbonyl)phenyl)-4-(dimethylamino)but-2-enamide.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Bataille, Carole J. R. published the artcileThiazolidine derivatives as potent and selective inhibitors of the PIM kinase family, Synthetic Route of 634905-21-8, the publication is Bioorganic & Medicinal Chemistry (2017), 25(9), 2657-2665, database is CAplus and MEDLINE.

The PIM family of serine/threonine kinases have become an attractive target for anti-cancer drug development, particularly for certain hematol. malignancies. Here, we describe the discovery of a series of inhibitors of the PIM kinase family using a high throughput screening strategy. Through a combination of mol. modeling and optimization studies, the intrinsic potencies and mol. properties of this series of compounds was significantly improved. An excellent pan-PIM isoform inhibition profile was observed across the series, while optimized examples show good selectivity over other kinases. Two PIM-expressing leukemic cancer cell lines, MV4-11 and K562, were employed to evaluate the in vitro anti-proliferative effects of selected inhibitors. Encouraging activities were observed for many examples, with the best example (44) giving an IC₅₀ of 0.75 μM against the K562 cell line. These data provide a promising starting point for further development of this series as a new cancer therapy through PIM kinase inhibition.

Bioorganic & Medicinal Chemistry published new progress about 634905-21-8. 634905-21-8 belongs to piperidines, auxiliary class Piperidine,Boronic acid and ester,Benzene,Boronic Acids,Boronic acid and ester, name is (3-(Piperidin-1-yl)phenyl)boronic acid, and the molecular formula is C11H16BNO2, Synthetic Route of 634905-21-8.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Gordon, Richard K. published the artcileDistance geometry of α-substituted 2,2-diphenylpropionate antimuscarinics, SDS of cas: 13444-24-1, the publication is Molecular Pharmacology (1989), 36(5), 766-72, database is CAplus and MEDLINE.

Quant. relationships between pharmacol. activities and phys. properties of a series of 2,2-diphenylpropionate compounds were used to define the topog. of the antagonist binding site of muscarinic receptors. XICAMM, a computer mol. modeling program, was used to calculate geometric and topol. values of the compounds The compounds were tested for their antimuscarinic activities by inhibition of [N-methyl-³H]scopolamine binding to the muscarinic receptors of N4TG1 neuroblastoma cells, by inhibition of carbachol-induced α-amylase release from rat pancreas acini, and by blocking acetylcholine-induced contraction of guinea pig ileum. To evaluate only the effect of the bond distance on the potency of the synthesized antimuscarinics, the compounds were designed to contain as many constant features as possible. Neither the hydrophobic nor the ester moieties of the compounds were changed, and the rings containing the protonated N saturated and restricted. The antimuscarinic activities obtained from the 3 assays correlated with each other, with the exception of 2 compounds The 2 compounds demonstrated specificity for the M3 muscarinic receptor subtype in the pancreas. The antimuscarinic activities were related to the bond distances between the carbonyl O (constant electroneg. locus) and the protonated N (center of cationic charge) of the 2,2-diphenylpropionate compounds Parabolic relationships between the pharmacol. activities and bond distances were empirically established. The shortest calculated bond distance of these compounds was ∼4.4 Å, whereas the longest was ∼5.9 Å. The maximum antimuscarinic potency was observed with a calculated bond distance of ∼5.2 Å in all 3 assays.

Molecular Pharmacology published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, SDS of cas: 13444-24-1.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Leadbetter, Elizabeth A. published the artcileNK T cells provide lipid antigen-specific cognate help for B cells, COA of Formula: C11H15NOS, the publication is Proceedings of the National Academy of Sciences of the United States of America (2008), 105(24), 8339-8344, database is CAplus and MEDLINE.

The mechanisms of T cell help for production of antilipid antibodies are largely unknown. This study shows that invariant NK T cells (iNK T cells) and B cells cooperate in a model of antilipid antigen-specific antibody responses. We use a model haptenated lipid mol., 4-hydroxy-3-nitrophenyl-αGalactosylCeramide (NP-αGalCer), to demonstrate that iNK T cells provide cognate help to lipid-antigen-presenting B cells. B cells proliferate and IgG anti-NP is produced from in vivo-immunized mice and in vitro cocultures of B and NK T cells after exposure to NP-αGalCer, but not closely related control glycolipids. This B cell response is absent in CD1d^-/- and Jα18^-/- mice but not CD4^-/- mice. The antibody response to NP-αGalCer is dominated by the IgM, IgG3, and IgG2c isotypes, and marginal zone B cells stimulate better in vitro lipid antigen-driven proliferation than follicular B cells, suggesting an important role for this B cell subset. iNK T cell help for B cells is shown to involve cognate help from CD1d-instructed lipid-specific iNK T cells, with help provided via CD40L, B7-1/B7-2, and IFN-γ, but not IL-4. This model provides evidence of iNK T cell help for antilipid antibody production, an important aspect of infections, autoimmune diseases, and vaccine development. Our findings also now allow prediction of those microbial antigens that would be expected to elicit cognate iNKT cell help for antibody production, namely those that can stimulate iNKT cells and at the same time have a polar moiety that can be recognized by antibodies.

Proceedings of the National Academy of Sciences of the United States of America published new progress about 4972-31-0. 4972-31-0 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-(Phenylsulfinyl)piperidine, and the molecular formula is C11H15NOS, COA of Formula: C11H15NOS.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Bellomo, Piero published the artcileSynthesis and antibacterial activity of some derivatives of tolypomycinone. Relation between structure and activity in ansamycins, COA of Formula: C7H16N2, the publication is Journal of Medicinal Chemistry (1977), 20(10), 1287-91, database is CAplus and MEDLINE.

A series of 29 3-aminotolypomycinone derivatives and 3,16-diamino-16,17-dihydrotolypomycinone derivatives were prepared by addition of a primary or secondary amine to tolypomycinone, and 3-(methylamino)-16,17-dihydrotolypomycinone was prepared by addition of MeNH₂ to 16,17-dihydrotolypomycinone. One of the most active compounds, 3-[2-(N-morpholyl)ethylamino]tolypomycinone (I), had enhanced stability and prolonged activity against Staphylococcus aureus in acid and alk. solutions as compared to tolypomycin Y. In vitro tests showed high antibacterial activity for several compounds against S. aureus and 3 strains of gram-neg. bacteria. Structure-activity relations are discussed.

Journal of Medicinal Chemistry published new progress about 14613-37-7. 14613-37-7 belongs to piperidines, auxiliary class Piperidine,Amine, name is (1-Methylpiperidin-3-yl)methanamine, and the molecular formula is C7H16N2, COA of Formula: C7H16N2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem