Month: November 2022

Wang, Yang published the artcileDihydropyrazole derivatives as telomerase inhibitors: Structure-based design, synthesis, SAR and anticancer evaluation in vitro and in vivo, Name: Piperidine-4-carboxamide, the publication is European Journal of Medicinal Chemistry (2016), 231-251, database is CAplus and MEDLINE.

In order to carry out more rational design, based on structure-based drug design, several series of N-substituted-dihydropyrazole derivatives, totally 78 compounds as potential human telomerase inhibitors were designed and synthesized. The results demonstrated that some compounds had potent anticancer activity against four tumor cell lines, and showed good selectivity on tumor cells over somatic cells. By the modified TRAP assay, compound I exhibited the most potent inhibitory activity against telomerase with an IC₅₀ value of 0.98 μM. In vivo evaluation results indicated that compound I could inhibit growth of S180 and HepG2 tumor-bearing mice, and it also significantly enhanced the survival rate of EAC tumor-bearing mice. The further results in vivo confirmed that it could significantly improve pathol. changes of N,N-diethylnitrosamine (DEN)-induced rat hepatic tumor. These data support further studies to assess rational design of more efficient telomerase inhibitors in the future.

European Journal of Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C9H8BNO2, Name: Piperidine-4-carboxamide.

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

Xin, Chao published the artcileA novel melanin complex displayed the affinity to HepG2 cell membrane and nucleus, Quality Control of 39546-32-2, the publication is Materials Science & Engineering, C: Materials for Biological Applications (2021), 111923, database is CAplus and MEDLINE.

Chitosan-melanin complex from Catharsius molossus L. has proven to possess superior pharmaceutical excipient performance and may be the new source of water-soluble protein-free natural melanin. Herein, it was enzymically hydrolyzed into the chitooligosaccharide-melanin complex (CMC) whose main chem. units were composed of eumelanin and chitooligosaccharides and showed three-layer structures. Addnl., this biomacromol. could self-assemble into 40 nm nanoparticles (CMC Nps) in a weakly acidic aqueous solution Interestingly, CMC displayed strong affinity for cell membrane by binding the phosphatidylserine, glycoprotein, glycolipids and glycosaminoglycans accumulated on the surface of tumor cells, notably, CMC Nps could enter cells and mainly target the nucleus by interacting with DNA and/or RNA substrates located around the nucleus to disrupt the proliferation and apoptosis processes. The findings suggest CMC may be the novel material for subcellular organelle targeting of cancer cells.

Materials Science & Engineering, C: Materials for Biological Applications published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C11H19N, Quality Control of 39546-32-2.

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

Mo, Jun published the artcileDesign, synthesis, in vitro and in vivo evaluation of benzylpiperidine-linked 1,3-dimethylbenzimidazolinones as cholinesterase inhibitors against Alzheimer’s disease, HPLC of Formula: 39546-32-2, the publication is Journal of Enzyme Inhibition and Medicinal Chemistry (2020), 35(1), 330-343, database is CAplus and MEDLINE.

Cholinesterase inhibitor plays an important role in the treatment of patients with Alzheimer’s disease (AD). Herein, we report the medicinal chem. efforts leading to a new series of 1,3-dimethylbenzimidazolinone derivatives Among the synthesized compounds, and showed submicromolar IC₅₀ values (, eeAChE IC₅₀ = 0.39 ± 0.11μM; , eqBChE IC₅₀ = 0.16 ± 0.04μM) towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Kinetic and mol. modeling studies revealed that and act in a competitive manner. and showed neuroprotective effect against H₂O₂-induced oxidative damage on PC12 cells. This effect was further supported by their antioxidant activity determined in a DPPH assay in vitro. Morris water maze test confirmed the memory amelioration effect of the two compounds in a scopolamine-induced mouse model. Moreover, the hepatotoxicity of and was lower than tacrine. In summary, these data suggest and are promising multifunctional agents against AD.

Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, HPLC of Formula: 39546-32-2.

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

Sundriyal, Sandeep published the artcileHistone lysine methyltransferase structure activity relationships that allow for segregation of G9a inhibition and anti-Plasmodium activity, Application In Synthesis of 39546-32-2, the publication is MedChemComm (2017), 8(5), 1069-1092, database is CAplus and MEDLINE.

Plasmodium falciparum HKMTs (PfHKMTs) play a key role in controlling Plasmodium gene expression and represent exciting new anti-malarial epigenetic targets. Using an inhibitor series derived from the diaminoquinazoline HKMT inhibitory chemotype, we have previously identified compounds with highly promising antimalarial activity, including irreversible asexual cycle blood stage-independent cytotoxic activity at nM concentrations, oral efficacy in in vivo models of disease, and the unprecedented ability to reactivate dormant liver stage parasites (hypnozoites). However, future development of this series will need to address host vs. parasite selectivity, where inhibitory activity against human G9a is removed from the lead compounds, while maintaining potent anti-Plasmodium activity. Herein, we report an extensive study of the SAR of this series against both G9a and P. falciparum. We have identified key SAR features which demonstrate that high parasite vs. G9a selectivity can be achieved by selecting appropriate substituents at position 2, 4 and 7 of the quinazoline ring. We have also, in turn, discovered that potent G9a inhibitors can be identified by employing a 6-carbon ‘Nle mimic’ at position 7. Together, this data suggests that while broadly similar, the G9a and potential PfHKMT target(s) binding pockets and/or binding modes of the diaminoquinazoline analogs exhibit clear and exploitable differences. Based on this, we believe this scaffold to have clear potential for development into a novel anti-malarial therapeutic.

MedChemComm published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H8N2, Application In Synthesis of 39546-32-2.

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

Zuo, Zeping published the artcileDesign and biological evaluation of tetrahydropyridine derivatives as novel human GPR119 agonists, Recommanded Product: Piperidine-4-carboxamide, the publication is Bioorganic & Medicinal Chemistry Letters (2020), 30(4), 126855, database is CAplus and MEDLINE.

A series of novel tetrahydropyridine derivatives were prepared and evaluated using cell-based measurements. Systematic optimization of general structure G-1 led to the identification of compound 4-((4-(1H-tetrazol-1-yl)phenoxy)methyl)-2-(1-(5-ethylpyrimidin-2-yl)1,2,3,6-tetrahydropyridin-4-yl)thiazole (EC₅₀ = 4.9 nM) and 2-(1-(5-ethylpyrimidin-2-yl)-1,2,3,6-tetrahydropyridin-4-yl)-4-((2-fluoro-4(1H-tetrazol-1-yl)phenoxy)methyl)thiazole (EC₅₀ = 8.8 nM) with high GPR119 agonism activity and moderate clog P. Through single and long-term pharmacodynamic experiments, compound 4-((4-(1H-tetrazol-1-yl)phenoxy)methyl)-2-(1-(5-ethylpyrimidin-2-yl)1,2,3,6-tetrahydropyridin-4-yl)thiazole showed a hypoglycemic effect and may have an effect on improving basal metabolic rate in DIO mice. Both in vitro and in vivo tests indicated that compound 4-((4-(1H-tetrazol-1-yl)phenoxy)methyl)-2-(1-(5-ethylpyrimidin-2-yl)1,2,3,6-tetrahydropyridin-4-yl)thiazole was a potential potent GPR119 agonist in allusion to T2DM treatment.

Bioorganic & Medicinal Chemistry Letters published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C9H7NO2, Recommanded Product: Piperidine-4-carboxamide.

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

Del Bubba, Massimo published the artcileEnantiomeric resolution of chiral aromatic sulfoxides on non-commercial microcrystalline cellulose triacetate and commercial cellulose acetate plates, Quality Control of 4972-31-0, the publication is Journal of Planar Chromatography–Modern TLC (2012), 25(6), 498-503, database is CAplus.

This paper reports a number of original thin-layer chromatog. enantioseparations of chiral sulfoxides that are important for their use as drugs and drug metabolites or pesticides, obtained by elution with aqueous-alc. mixtures at different ratios. Noncom. microcrystalline cellulose triacetate and com. cellulose acetate (CEL 300-10/a.c., Macherey-Nagel) plates were compared for their chiral resolution power, evidencing the much better performances of the former. The linearity of the densitometric response as a function of the amount of each enantiomer applied to the plate was studied for selected compounds Correlation coefficients higher than or equal to 0.99 were obtained in all cases, and the feasibility of the quantification of the individual enantiomers at tens to hundreds of nanograms spotted was demonstrated.

Journal of Planar Chromatography–Modern TLC 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, Quality Control of 4972-31-0.

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

Del Bubba, Massimo published the artcileEnantiomeric resolution of chiral aromatic sulfoxides on non-commercial cellulose tribenzoate plates, Quality Control of 4972-31-0, the publication is Journal of Planar Chromatography–Modern TLC (2012), 25(3), 214-219, database is CAplus.

This paper reports a number of original thin-layer chromatog. enantioseparations of chiral sulfoxides that are important for their use as drugs and drug metabolites, pesticides, or chiral auxiliaries, obtained by elution with alcs. or aqueous-alc. mixtures at different ratios on cellulose tribenzoate. Detection was performed by exposing the plates to iodine vapor, followed by densitometry at 410 nm. Under these exptl. conditions, ten of the eighteen chiral aromatic sulfoxides studied were baseline or partially resolved, thus providing useful chromatog. information for this important class of racemic compounds Data obtained with cellulose tribenzoate were compared to those achieved with microcrystalline cellulose triacetate for the same group of chiral sulfoxides, evidencing an interesting complementary behavior of the two stationary phases.

Journal of Planar Chromatography–Modern TLC 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, Quality Control of 4972-31-0.

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

Demeter, Fruzsina published the artcileAn Efficient Synthesis of the Pentasaccharide Repeating Unit of Pseudomonas aeruginosa Psl Exopolysaccharide, Safety of 1-(Phenylsulfinyl)piperidine, the publication is Synlett (2020), 31(5), 469-474, database is CAplus.

Pseudomonas aeruginosais a biofilm-forming Gram-neg. bacterium and a leading cause of life-threatening nosocomial infections. The polysaccharide synthesis locus (Psl) exopolysaccharide of P. aeruginosais a key constituent of the defending bacterial biofilm layer and is a promising therapeutic target for resistant species. The Psl exopolysaccharide is built up from repeating pentasaccharide units which contain one α- and two β-mannosidic linkages, and one L-rhamnose and one D-glucose moieties. The preparation of this pentasaccharide was first described by Boons et al. in a 34-step synthesis. Based on their work, we have developed a new and effective pathway for the synthesis of the repeating pentasaccharide unit of the Psl exopolysaccharide. We have succeeded in simplifying the synthesis of the L-rhamnose and the α-selective D-mannose building blocks. Furthermore, taking advantage of a chemoselective pre-activation-based β-mannosylation, we directly prepare a thioglycoside disaccharide donor and use it in the next coupling reaction without further transformation. The pentasaccharide, in the form of a p-methoxyphenyl glycoside, is prepared in 26 steps, which is suitable for biol. testing.

Synlett 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, Safety of 1-(Phenylsulfinyl)piperidine.

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

Murugesan, Kathiravan published the artcileA General Catalyst Based on Cobalt Core-Shell Nanoparticles for the Hydrogenation of N-Heteroarenes Including Pyridines, Application of Piperidine-4-carboxamide, the publication is Angewandte Chemie, International Edition (2020), 59(40), 17408-17412, database is CAplus and MEDLINE.

Herein, we report the synthesis of specific silica-supported Co/Co₃O₄ core-shell based nanoparticles prepared by template synthesis of cobalt-pyromellitic acid on silica and subsequent pyrolysis. The optimal catalyst material allows for general and selective hydrogenation of pyridines, quinolines, and other heteroarenes including acridine, phenanthroline, naphthyridine, quinoxaline, imidazo[1,2-a]pyridine, and indole under comparably mild reaction conditions. In addition, recycling of these Co nanoparticles and their ability for dehydrogenation catalysis are showcased.

Angewandte Chemie, International Edition published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Application of Piperidine-4-carboxamide.

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

Najer, Henri published the artcileSpasmolytically active α-phenyl-α-tertiary-aminoacetates, Application of 1-Ethylpiperidin-3-ol, the publication is Bulletin de la Societe Chimique de France (1958), 355-9, database is CAplus.

cf. C.A. 52, 10073a. To assess their spasmolytic activity with respect to acetylcholine and BaCl₂, beta;-tertiary-aminoethyl β-tertiary-aminoethoxyethyl α-phenyl-α-tertiary-aminoacetate dihydrochlorides, RPhCHCO₂R¹.2HCl (R¹ = CH₂CH₂R²) (I) and (R¹ =CH₂CH₂OCH₂CH₂R²) (II) were prepared Treatment of the appropriate alc in Et₂O at 0° with PhCHClCOCl gave α-phenyl-α-chloroacetate HCl salts, PhCHClCO₂R¹.HCl (R¹ = CH₂CH₂R²) (III), and (R¹ = CH₂CH₂OCH₂CH₂R²) (IV). The unstable corresponding bases (V, VI) refluxed several hrs. in C₆H₆ with a suitable secondary amine gave the bases of I and II (VII, VIII). The toxicity (L.D.₅₀ in mg./kg.) was determined by intravenous injection in white mice according to the method of Kaerber and Behrens. The spasmolytic activity on isolated guinea pig intestine against acetylcholine spasm and BaCl₂ spasm was measured in comparison with Ph₂CHCO₂CH₂CH₂NEt₂.HCl (IX) and papaverine hydrochloride (X), resp. Piperidine (76.5 g.) and 50 g. AcOCH₂CH₂OCH₂CH₂Cl in 75 ml. absolute alc. heated 18 hrs. in a sealed tube, the cooled solution evaporated in vacuo, the residue in 30 ml. H₂O made alk. with 40 ml. 40% Na₂CO₃, the oily product extracted 4 times with 100 ml. Et₂O, the dried extracts (Na₂SO₄) evaporated, the residual oil distilled gave 39.5 g. β-piperidinoethoxyethanol, b₃ 105-6°; HCl salt, m. 120° (Me₂CO) (all m.ps. on Maquenne block). Similarly was prepared 70% β-morpholinoethoxyethanol, b₃ 106-8°; HCl salt, m. 157° (iso-PrOH). PhCHClCOCl (245 g.) in 1 l. anhydrous Et₂O at 0° stirred 1 hr. with gradual addition of 151 g. Et₂NCH₂CH₂OH in 800 ml. Et₂O and the mixture kept 1 hr. at 0° and 24 hrs. at room temperature, filtered, and the Et₂O-washed product air-dried gave III (R² = NEt₂) (IIIa). IIIa (357 g.) in 1 l. H₂O adjusted to pH 9 with saturated aqueous Na₂CO₃ and the oily product extracted 4 times with 500 ml. Et₂O gave 236 g. crude V (R² = NEt₂) (Va) suitable for immediate condensation with the appropriate secondary amine. PhCHClCOCl (48 g.) in 200 ml. Et₂O at 0° stirred with gradual addition in 20 min. of 32 g. β-(1,2,5,6-tetrahydro-1-pyridyl)ethanol (cf. C., et al., loc. cit.) in 200 ml. Et₂O and the mixture kept 30 min. at 0° and 24 hrs. at room temperature gave 50 g. oily III (R² = NC₅H₉). Similarly were prepared the analogous hydrochlorides, III and IV (series, R², m.p. (solvent), and % yield given): III, NEt₂, 123° (iso-BuOH), 91; III, NC₄H₈O (= morpholino), 166° (iso-BuOH), 74; 3-(N-ethylpiperidinyl), 166° (iso-PrOH) (hygroscopic), 99; IV, NEt₂, oil (-), -; IV, NC₅H₁₀ (= piperidino), 116° (AcEt), 98; IV, NC₄H₈O, 84° (EtOAc), 80. Va (56.4 g.) in 250 ml. dry C₆H₆ refluxed 8 hrs. with 34.8 g. 1,2,5,6-tetrahydropyridine, the cooled mixture filtered, the precipitated HCl salt washed repeatedly with dry C₆H₆, the filtrate and washings evaporated in vacuo, the residue in 200 ml. H₂O extracted 3 times with 200 ml. Et₂O and the dried extract evaporated gave VII (R = NC₅H₈, R² = NEt₂), converted in dry Et₂O by passage of dry HCl to the corresponding I; di-HBr salt, m. 197-200° (iso-PrOH). Similarly were prepared the analogous bases VII, VIII and the corresponding di-HCl salts [series, R, R², b.p./mm. and % yield of base, m.p. (solvent) of dihydrochlorides, toxicity (L.D.₅₀), and spasmolytic activity in respect to acetylcholine and BaCl₂ given]: I (Ia), NC₅H₁₀, NEt₂, 163-4°/0.2, 68, 214-15° (alc.-Et₂O), 55, 1.30, 0.9; I (Ib) NC₅H₁₀, NC₅H₁₀, 169-70°/0.4 79, 238° (iso-PrOH), 80, 2, 6; I, NC₅H₁₀, C₇H₁₄N (= 1-ethyl-3-piperidyl), 170-2°/0.5, 61, 235° (alc.-Et₂O), 85, 0.2, 0.2; I, NC₅H₁₀, NC₅H₈, 180-2°/0.5, 90, 227-8° (iso-PrOH), 92, 0.8, 3; I, NC₅H₁₀, NC₄H₈O, 180-3°/0.09, 70, 195-200° (alc.-Et₂O), 205, 0.02, 0.1; II, NC₅H₁₀, NEt₂, 186-7°/0.4, 74, paste (-), 57, 0.75, 1.0; II, NC₅H₁₀, NC₅H₁₀, 190-2°/0.2, 45, 214° (iso-PrOH), 77, 0.10, 0.7; II, NC₅H₁₀, NC₄H₈O, 218-20°/1.0, 72, 211-12° (iso-PrOH), 210, 0.02, 0.2; I, 3-methylpiperidino, NEt₂, 164-6°/0.5-0.6, 68, 227° (alc.-Et₂O), 67.5, 0.25, 1.0; I, 3-methylpiperidino, NC₅H₁₀, 180-2°/0.6-0.8, 69, 229° (alc.-Et₂O), 75, 0.40, 1.2; I, 3-methylpiperidino, C₇H₁₄N, 177/0.4, 64, 216° (alc.-Et₂O), 90, 0.07, 1.0; I, 4-methylpiperidino, NEt₂, 192-3°/3.0, 42, 225° (alc.-EtOAc), 80, 0.75, 6; I, 4-methylpiperidino, NC₅H₁₀, 185-7°/1.0, 67, 239° (alc.-Et₂O), 70, 0.45, 1.0; I, 4-methylpiperidino, C₇H₁₄N, 168-9°/0.2, 61, 233° (alc.-Et₂O), 80, 0.15, 0.8; I, NC₅H₈, NEt₂, 167-70°/0.8-0.9, 69, hygroscopic (iso-PrOH-Et₂O), 97, 1.0, 5.0; I, NC₅H₈, NC₅H₁₀, 215-18°/1.5, 49, 236° (iso-PrOH), 92.5, 1.0, 1.0; I, NC₅H₈, NC₅H₈, 189-90°/0.8, 70, 222-4° (iso-PrOH), 107, 0.5, 4.0; II, NC₅H₈, NEt₂, 189-91°/0.3, 42, 161° (Me₂CO), 55, 0.5, 1.0; II, NC₅H₈, NC₅H₁₀, 199-200°/0.5, 76, hygroscopic (-), 82, 0.05, 1.5; II, NC₅H₈, NC₄H₈O, 203-5°/0.2, 57, 198° (iso-PrOH), 285, 0.01, 0.4 I, NC₄H₈, NEt₂, 138-40°/0.05, 60, 135-40° (hygroscopic), 117.5, 1.0, 1.3; I, NC₄H₈, NC₅H₁₀, 168-70°/0.5, 66, 218° (alc.-Et₂O), 87.5, 1.0, 0.5; I, NC₄H₈, C₇H₁₄N, 160-2°/0.5, 70, hygroscopic (iso-PrOH-Et₂O), 82.5, 0.05, 1.0; I, NC₄H₈O, NEt₂, 154-6°/0.05-0.06, 56, 217° (AcEt-alc.), 275, 0.03, 0.9; I, NC₄H₈O, NC₅H₁₀, 174-6°/0.05, 36, 170-5° (hygroscopic), 138, 0.1, 0.1; I, NC₄H₈O, C₇H₁₄N, 170-4°/0.7, 60, 214° (iso-PrOH-Et₂O), 180, less than 0.1, 0.2. In comparison, IX and X had L.D.₅₀ 42 and 30 and spasmolylic activities 1 against acetylcholine and 1 against BaCl₂, resp. The compounds with most favorable spasmoltyic action are I in which R is piperidino or 1,2,5,6-tetrahydropyridyl, and whatever the nature of R the antiacetylcholenic action is greatest when R² is NEt₂ or piperidino. No particular conclusion was made as to the relation between the nature of R² and the musculotropic activity against BaCl₂. Ib had the most favorable activities of all the compounds examined and had a favorable therapeutic coefficient in comparison with IX and X.

Bulletin de la Societe Chimique de France 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, Application of 1-Ethylpiperidin-3-ol.

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