Tag: M.W=100-150

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

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

Gao, Yinyi published the artcileDevelopment of coumarine derivatives as potent anti-filovirus entry inhibitors targeting viral glycoprotein, Quality Control of 39546-32-2, the publication is European Journal of Medicinal Chemistry (2020), 112595, database is CAplus and MEDLINE.

Filoviruses, including Ebolavirus (EBOV), Marburgvirus (MARV) and Cuevavirus, cause hemorrhagic fevers in humans with up to 90% mortality rates. In the 2014-2016 West Africa Ebola epidemic, there are 15,261 laboratory confirmed cases and 11,325 total deaths. The lack of effective vaccines and medicines for the prevention and treatment of filovirus infection in humans stresses the urgency to develop antiviral therapeutics against filovirus-associated diseases. Our previous study identified a histamine receptor antagonist compound CP19 as an entry inhibitor against both EBOV and MARV. The preliminary structure-activity relationship (SAR) studies of CP19 showed that its piperidine, coumarin and linker were related with its antiviral activities. In this study, we performed detailed SAR studies on these groups with synthesized CP19 derivatives We discovered that 1) the piperidine group could be optimized with heterocycles, 2) the substitution groups of C3 and C4 of coumarin should be relatively large hydrophobic groups and 3) the linker part should be least substituted. Based on the SAR anal., we synthesized compound as a potent entry inhibitor of EBOV and MARV (IC₅₀ = 0.5μM for EBOV and 1.5μM for MARV). The mutation studies of Ebola glycoprotein and mol. docking studies showed that the coumarin and its substituted groups of compound 32 bind to the pocket of Ebola glycoprotein in a similar way to the published entry inhibitor compound 118a. However, the carboxamide group of compound 32 does not have strong interaction with N61 as compound 118a does. The coumarin skeleton structure and the binding model of compound 32 elucidated by this study could be utilized to guide further design and optimization of entry inhibitors targeting the filovirus glycoproteins.

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 C6H12N2O, Quality Control of 39546-32-2.

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

Chen, Lixue published the artcileThe synthesis of 4-arylamido-2-arylaminoprimidines as potent EGFR T790M/L858R inhibitors for NSCLC, Application In Synthesis of 39546-32-2, the publication is Bioorganic & Medicinal Chemistry (2018), 26(23-24), 6087-6095, database is CAplus and MEDLINE.

A series of 4-arylamido-2-arylaminoprimidines bearing acrylamide pharmacophore were synthesized as potent EGFR^T790M/L858R inhibitors among which I [R¹ = H, NR²R³ = N(CH₂CH₂)₂CHCONH₂] (IC₅₀ = 0.5872 nM), I [R¹ = H, NR²R³ = NMe₂] (IC₅₀ = 2.213 nM), or I [R¹ = 3,4-(MeO)₂, NR²R³ = N(CH₂CH₂)₂NMe] (II) (IC₅₀ = 12.57 nM) showed more potent anti-EGFR^T790M/L858R activity compared with AZD-9291 (IC₅₀ = 20.80 nM) and possessed high SI displaying 307.6, 56.5, or 12.5 for EGFR^T790M/L858R over the wild-type resp. II also showed pretty good activity against H 1975 cells with an IC₅₀ of 1.664 μM and exhibited low toxicity against the normal HBE cells (IC₅₀ > 20 μM). II had moderate selectivity for H 1975 over A 431 (SI = 7.0) and the other selected cell lines. Morphol. staining results further indicated that II could promote apoptosis. Hence, II was a promising compound for further investigation as a potential EGFR^T790M/L858R inhibitor for the treatment of NSCLC.

Bioorganic & 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, Application In Synthesis of 39546-32-2.

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

Kim, Hyojin published the artcileSynthesis and biological evaluation of thiazole derivatives as GPR119 agonists, Category: piperidines, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(23), 5213-5220, database is CAplus and MEDLINE.

A series of 4-(phenoxymethyl)thiazole derivatives was synthesized and evaluated for their GPR119 agonistic effect. Several 4-(phenoxymethyl)thiazoles with pyrrolidine-2,5-dione moieties showed potent GPR119 agonistic activities. Among them, compound I (R = F, Me) showed good in vitro activity with an EC₅₀ value of 49 nM and 18 nM, resp. with improved human and rat liver microsomal stability compare with MBX-2982. Compound I (R = F, Me) did not exhibit significant CYP inhibition, hERG binding, and cytotoxicity. Moreover, these compounds lowered the glucose excursion in mice in an oral glucose-tolerance test.

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 C6H12N2O, Category: piperidines.

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

Mallinger, Aurelie published the artcileDiscovery of Potent, Orally Bioavailable, Small-Molecule Inhibitors of WNT Signaling from a Cell-Based Pathway Screen, Product Details of C6H12N2O, the publication is Journal of Medicinal Chemistry (2015), 58(4), 1717-1735, database is CAplus and MEDLINE.

WNT signaling is frequently deregulated in malignancy, particularly in colon cancer, and plays a key role in the generation and maintenance of cancer stem cells. The authors report the discovery and optimization of a 3,4,5-trisubstituted pyridine, 1-(3,5-Dichloropyridin-4-yl)piperidine-4-carboxamide (9), using a high-throughput cell-based reporter assay of WNT pathway activity. The authors demonstrate a twisted conformation about the pyridine-piperidine bond of (9) by small-mol. x-ray crystallog. Medicinal chem. optimization to maintain this twisted conformation, cognisant of physicochem. properties likely to maintain good cell permeability, led to 8-[3-Chloro-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pyridin-4-yl]-2,8-diazaspiro[4,5]decan-1-one (74) (CCT251545), a potent small-mol. inhibitor of WNT signaling with good oral pharmacokinetics. The authors demonstrate inhibition of WNT pathway activity in a solid human tumor xenograft model with evidence for tumor growth inhibition following oral dosing. This work provides a successful example of hypothesis-driven medicinal chem. optimization from a singleton hit against a cell-based pathway assay without knowledge of the biochem. target.

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 C6H12N2O, Product Details of C6H12N2O.

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

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

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

Kosak, Urban published the artcileDevelopment of an in-vivo active reversible butyrylcholinesterase inhibitor, HPLC of Formula: 39546-32-2, the publication is Scientific Reports (2016), 39495, database is CAplus and MEDLINE.

Alzheimer’s disease (AD) is characterized by severe basal forebrain cholinergic deficit, which results in progressive and chronic deterioration of memory and cognitive functions. Similar to acetylcholinesterase, butyrylcholinesterase (BChE) contributes to the termination of cholinergic neurotransmission. Its enzymic activity increases with the disease progression, thus classifying BChE as a viable therapeutic target in advanced AD. Potent, selective and reversible human BChE inhibitors were developed. The solved crystal structure of human BChE in complex with the most potent inhibitor reveals its binding mode and provides the mol. basis of its low nanomolar potency. Addnl., this compound is noncytotoxic and has neuroprotective properties. Furthermore, this inhibitor moderately crosses the blood-brain barrier and improves memory, cognitive functions and learning abilities of mice in a model of the cholinergic deficit that characterizes AD, without producing acute cholinergic adverse effects. Our study provides an advanced lead compound for developing drugs for alleviating symptoms caused by cholinergic hypofunction in advanced AD.

Scientific Reports 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