Month: December 2022

Pu, Szu-Yuan published the artcileOptimization of Isothiazolo[4,3-b]pyridine-Based Inhibitors of Cyclin G Associated Kinase (GAK) with Broad-Spectrum Antiviral Activity, Recommanded Product: Piperidine-4-carboxamide, the publication is Journal of Medicinal Chemistry (2018), 61(14), 6178-6192, database is CAplus and MEDLINE.

There is an urgent need for strategies to combat dengue and other emerging viral infections. We reported that cyclin G-associated kinase (GAK), a cellular regulator of the clathrin-associated host adaptor proteins AP-1 and AP-2, regulates intracellular trafficking of multiple unrelated RNA viruses during early and late stages of the viral lifecycle. We also reported the discovery of potent, selective GAK inhibitors based on an isothiazolo[4,3-b]pyridine scaffold, albeit with moderate antiviral activity. Here, we describe our efforts leading to the discovery of novel isothiazolo[4,3-b]pyridines that maintain high GAK affinity and selectivity. These compounds demonstrate improved in vitro activity against dengue virus, including in human primary dendritic cells, and efficacy against the unrelated Ebola and chikungunya viruses. Moreover, inhibition of GAK activity was validated as an important mechanism of antiviral action of these compounds These findings demonstrate the potential utility of a GAK-targeted broad-spectrum approach for combating currently untreatable emerging viral infections.

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, Recommanded Product: Piperidine-4-carboxamide.

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

Baradwaj, Aditya G. published the artcileImpact of the Addition of Redox-Active Salts on the Charge Transport Ability of Radical Polymer Thin Films, Recommanded Product: 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, the publication is Macromolecules (Washington, DC, United States) (2016), 49(13), 4784-4791, database is CAplus.

Radical polymers (i.e., macromols. composed of a nonconjugated polymer backbone and with stable radical sites present on the side chains of the repeat units) can transport charge in the solid state through oxidation-reduction (redox) reactions that occur between the electronically localized open-shell pendant groups. As such, pristine (i.e., not doped) thin films of these functional macromols. have elec. conductivity values on the same order of magnitude as some common electronically active conjugated polymers. However, unlike the heavily evaluated regime of conjugated polymer semiconductors, the impact of mol. dopants on the optical, electrochem., and solid-state electronic properties of radical polymers has not been established. Here, we combine a model radical polymer, poly(2,2,6,6-tetramethylpiperidinyloxy methacrylate) (PTMA), with a small mol. redox-active salt, 4-acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium tetrafluoroborate (TEMPOnium), to elucidate the effect of mol. doping on this emerging class of functional macromol. thin films. Note that the TEMPOnium salt was specifically selected because the cation in the salt has a similar mol. architecture to that of an oxidized repeat unit of the PTMA polymer. Importantly, we demonstrate that the addition of the TEMPOnium salt simultaneously alters the electrochem. environment of the thin film without quenching the number of open-shell sites present in the PTMA-based composite thin film. This environmental alteration changes the chem. signature of the PTMA thin films in a manner that modifies the elec. conductivity of the radical polymer-based composites. By decoupling the ionic and electronic contributions of the observed current passed through the PTMA-based thin films, we are able to establish how the presence of the redox-active TEMPOnium salts affects both the transient and steady-state transport abilities of doped radical polymer thin films. Addnl., at an optimal loading (i.e., doping d.) of the redox-active salt, the elec. conductivity of PTMA increased by a factor of 5 relative to that of pristine PTMA. Therefore, these data establish an underlying mechanism of doping in electronically active radical polymers, and they provide a template by which to guide the design of next-generation radical polymer composites.

Macromolecules (Washington, DC, United States) published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C11H21BF4N2O2, Recommanded Product: 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate.

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

Ketley, Ami published the artcileCDK12 inhibition reduces abnormalities in cells from patients with myotonic dystrophy and in a mouse model, COA of Formula: C30H32ClN7O2, the publication is Science Translational Medicine (2020), 12(541), eaaz2415, database is CAplus and MEDLINE.

Myotonic dystrophy type 1 (DM1) is an RNA-based disease with no current treatment. It is caused by a transcribed CTG repeat expansion within the 3�untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. Mutant repeat expansion transcripts remain in the nuclei of patients�cells, forming distinct microscopically detectable foci that contribute substantially to the pathophysiol. of the condition. Here, we report small-mol. inhibitors that remove nuclear foci and have beneficial effects in the HSA^LR mouse model, reducing transgene expression, leading to improvements in myotonia, splicing, and centralized nuclei. Using chemoproteomics in combination with cell-based assays, we identify cyclin-dependent kinase 12 (CDK12) as a druggable target for this condition. CDK12 is a protein elevated in DM1 cell lines and patient muscle biopsies, and our results showed that its inhibition led to reduced expression of repeat expansion RNA. Some of the inhibitors identified in this study are currently the subject of clin. trials for other indications and provide valuable starting points for a drug development program in DM1.

Science Translational Medicine 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, COA of Formula: C30H32ClN7O2.

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

Nandi, Jyoti published the artcileCombining Oxoammonium Cation Mediated Oxidation and Photoredox Catalysis for the Conversion of Aldehydes into Nitriles, Related Products of piperidines, the publication is Synlett (2018), 29(16), 2185-2190, database is CAplus.

A method to oxidize aromatic aldehydes to nitriles has been developed. It involves a dual catalytic system of 4-acetamido-TEMPO and visible-light photoredox catalysis. The reaction is performed using ammonium persulfate as both the terminal oxidant and nitrogen source.

Synlett published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C11H21BF4N2O2, Related Products of piperidines.

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

Rozanska, Xavier published the artcileQuantitative Kinetic Model of CO₂ Absorption in Aqueous Tertiary Amine Solvents, Quality Control of 13444-24-1, the publication is Journal of Chemical Information and Modeling (2021), 61(4), 1814-1824, database is CAplus and MEDLINE.

Aqueous tertiary amine solutions are increasingly used in industrial CO₂ capture operations because they are more energy-efficient than primary or secondary amines and demonstrate higher CO₂ absorption capacity. Yet, tertiary amine solutions have a significant drawback in that they tend to have lower CO₂ absorption rates. To identify tertiary amines that absorb CO₂ faster, it would be efficacious to have a quant. and predictive model of the rate-controlling processes. Despite numerous attempts to date, this goal has been elusive. The present computational approach achieves this goal by focusing on the reaction of CO₂ with OH^– forming HCO₃^–. The performance of the resulting model is demonstrated for a consistent exptl. data set of the absorption rates of CO₂ for 24 different aqueous tertiary amine solvents. The key to the new model’s success is the manner in which the free energy barrier for the reaction of CO₂ with OH^– is evaluated from the differences among the solvation free energies of CO₂, OH^–, and HCO₃^–, while the pK_a of the amines controls the concentration of OH^–. These solvation energies are obtained from mol. dynamics simulations. The exptl. value of the free energy of reaction of CO₂ with pure water is combined with information about measured rates of absorption of CO₂ in an aqueous amine solvent in order to calibrate the absorption rate model. This model achieves a relative accuracy better than 0.1 kJ mol^-1 for the free energies of activation for CO₂ absorption in aqueous amine solutions and 0.07 g L^-1 min^-1 for the absorption rate of CO₂. Such high accuracies are necessary to predict the correct exptl. ranking of CO₂ absorption rates, thus providing a quant. approach of practical interest.

Journal of Chemical Information and Modeling 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, Quality Control of 13444-24-1.

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

Tomlinson, Edward P. published the artcileTuning the Thermoelectric Properties of a Conducting Polymer through Blending with Open-Shell Molecular Dopants, Recommanded Product: 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, the publication is ACS Applied Materials & Interfaces (2015), 7(33), 18195-18200, database is CAplus and MEDLINE.

Polymer thermoelec. devices are emerging as promising platforms by which to convert thermal gradients into electricity directly, and poly(3,4-ethylene dioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS) is a leading candidate in a number of these thermoelec. modules. Here, we implement the stable radical-bearing small mol. 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO-OH) as an intermol. dopant in order to tune the elec. conductivity, thermopower, and power factor of PEDOT:PSS thin films. Specifically, we demonstrate that, at moderate loadings (�%, by weight) of the open-shell TEMPO-OH mol., the thermopower of PEDOT:PSS thin films is increased without a marked decline in the elec. conductivity of the material. This effect, in turn, allows for an optimization of the power factor in the composite organic materials, which is a factor of 2 greater than the pristine PEDOT:PSS thin films. Furthermore, because the loading of TEMPO-OH is relatively low, we observe that there is little change in either the crystalline nature or surface topog. of the composite films relative to the pristine PEDOT:PSS films. Instead, we determine that the increase in the thermopower is due to the presence of stable radical sites within the PEDOT:PSS that persist despite the highly acidic environment that occurs due to the presence of the poly(styrenesulfonate) moiety. Addnl., the oxidation-reduction-active (redox-active) nature of the TEMPO-OH small mols. provides a means by which to filter charges of different energy values. Therefore, these results demonstrate that a synergistic combination of an open-shell species and a conjugated polymer allows for enhanced thermoelec. properties in macromol. systems, and as such, it offers the promise of a new design pathway in polymer thermoelec. materials.

ACS Applied Materials & Interfaces published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C5H10Cl3O3P, Recommanded Product: 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate.

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

Lin, Kingson published the artcileHaloselective Cross-Coupling via Ni/Photoredox Dual Catalysis, Application In Synthesis of 219543-09-6, the publication is ACS Catalysis (2017), 7(8), 5129-5133, database is CAplus and MEDLINE.

The chemoselective functionalization of polyfunctional aryl linchpins is crucial for rapid diversification. Although well-explored for C_sp² and C_sp nucleophiles, the chemoselective introduction of C_sp³ groups remains notoriously difficult and is virtually undocumented using Ni catalysts. To fill this methodol. gap, a “haloselective” cross-coupling process of arenes bearing two halogens, I and Br, using ammonium alkylbis(catecholato)silicates, has been developed. Utilizing Ni/photoredox dual catalysis, C_sp³-C_sp² bonds can be forged selectively at the iodine-bearing carbon of bromo(iodo)arenes. The described high-yielding, base-free strategy accommodates various protic functional groups. Selective electrophile activation enables installation of a second C_sp³ center and can be done without the need for purification of the intermediate monoalkylated product.

ACS Catalysis published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C11H21BF4N2O2, Application In Synthesis of 219543-09-6.

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

Lien, Evan C. published the artcileLow glycaemic diets alter lipid metabolism to influence tumour growth, Recommanded Product: 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, the publication is Nature (London, United Kingdom) (2021), 599(7884), 302-307, database is CAplus and MEDLINE.

Dietary interventions can change metabolite levels in the tumor microenvironment, which might then affect cancer cell metabolism to alter tumor growth1-5. Although caloric restriction (CR) and a ketogenic diet (KD) are often thought to limit tumor progression by lowering blood glucose and insulin levels6-8, we found that only CR inhibits the growth of select tumor allografts in mice, suggesting that other mechanisms contribute to tumor growth inhibition. A change in nutrient availability observed with CR, but not with KD, is lower lipid levels in the plasma and tumors. Upregulation of stearoyl-CoA desaturase (SCD), which synthesizes monounsaturated fatty acids, is required for cancer cells to proliferate in a lipid-depleted environment, and CR also impairs tumor SCD activity to cause an imbalance between unsaturated and saturated fatty acids to slow tumor growth. Enforcing cancer cell SCD expression or raising circulating lipid levels through a higher-fat CR diet confers resistance to the effects of CR. By contrast, although KD also impairs tumor SCD activity, KD-driven increases in lipid availability maintain the unsaturated to saturated fatty acid ratios in tumors, and changing the KD fat composition to increase tumor saturated fatty acid levels cooperates with decreased tumor SCD activity to slow tumor growth. These data suggest that diet-induced mismatches between tumor fatty acid desaturation activity and the availability of specific fatty acid species determine whether low glycemic diets impair tumor growth.

Nature (London, United Kingdom) published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C20H22ClN3O3, Recommanded Product: 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide.

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

Gardner, T. S. published the artcileSynthesis of compounds for chemotherapy of tuberculosis. VII. Pyridine N-oxides with sulfur-containing groups, Application of Piperidine-4-carbothioamide, the publication is Journal of Organic Chemistry (1957), 984-6, database is CAplus.

cf. C.A. 51, 3610b. A number of C₅H₅N derivatives containing a CSNH moiety were prepared Isonicotinamide 1-oxide (Ia) (147 g.) refluxed 0.5 h. with 1.5 kg. POCl₃, the solution concentrated, poured on ice, and made alk., and the separated nitrile collected, the solution was extracted 5 times with CHCl₃, the solids also extracted with CHCl₃, and the combined extracts yielded 85 g. isonicotinonitrile 1-oxide (I), m. 229-30°. I (30 g.) in 300 mL. MeOH containing 30% NH₃ by weight and the solution left 2 days saturated with H₂S gave 12 g. thioisonicotinamide 1-oxide, m. 205-6° (H₂O). Thioisonicotinamide-HCl, orange colored solid, m. 231-2°(alc.). Nicotinonitrile 1-oxide (II) was obtained in 55% yield from nicotinamide 1-oxide by refluxing 0.5 h. with POCl₃. II (28 g.) in 300 mL. MeOH containing 20% NH₃ left 18 h. with H₂S gave 14 g. thionicotinamide 1-oxide, m. 161-4° (H₂O). Picolinamide (70 g.) heated 6 h. at 80° in a solution of 100 g. 40% AcO₂H and 300 mL. AcOH gave 51 g. picolinamide 1-oxide (III), m. 165-6° (MeOH). The investigation of the picolino-type N-oxide gave several anomalies. Thus P₂S₅ and K₂S in C₅H₅N with III deoxygenated the N-oxide and gave only thiopicolinamide. A mixture of 70 g. diatomaceous earth and 150 g. P₂O₅ refluxed 4 h. with 25 g. III in 500 mL. PhMe, the gummy mixture filtered on a dry Hyflo bed, the residue treated with H₂O and concentrated NH₄OH and extracted with CHCl₃, and the combined PhMe and CHCl₃ solutions concentrated gave 5 g. picolinonitrile 1-oxide, m. 122-3° (Et₂O). The reaction of refluxing POCl₃ on III rapidly deoxygenated the compound to give 2-picolinonitrile. In contrast, more than 6 h. refluxing POCl₃ was required to deoxygenate Ia to give isonicotinonitrile. 4-Aminopyridine 1-oxide-HCl (20 g.) refluxed 6 h. with 12.5 g. NH₄SCN in 250 mL. alc. gave 20 g. 4-pyridylthiourea 1-oxide, m. 126-7° (Me₂CO). 3-Bromopyridine 1-oxide-HCl (53.5 g.) in 100 mL. H₂O neutralized with dilute NaOH and extracted with CHCl₃ gave the free 3-bromopyridine 1-oxide which when refluxed 5 h. in 300 mL. alc. with 19 g. CS(NH₂)₂ gave 50 g. 2-(3′-pyridyl)-2-thiopseudourea 1′-oxide-HBr (IV), m. 145-7° (alc.). IV could not be decomposed to give 3-pyridinethiol 1-oxide using NaOH solution N-Ethylnicotinamide (60 g.) treated at 10-15° with 120 g. 40% AcO₂H in AcOH and concentrated at 80° gave 35 g. N-ethylnicotinamide 1-oxide, m. 123-4°. 3,5-Dibromopyridine (42 g.), 80 g. 40% AcO₂H in AcOH, and 300 mL. AcOH heated 3 h. at 80° and then 12 h. at 50° gave 30 g. 3,5-dibromopyridine 1-oxide (V), m. 143-4° (alc.). V (20 g.) refluxed 5 h. in 300 mL. alc. and 15 g. CS(NH₂)₂ gave 20 g. 2-(5′-bromo-3′-pyridyl)-2-thiopseudourea 1′-oxide-HBr, m. 162-3° (alc.). Thioisonicotinamide (Va) (25 g.) in 1 l. H₂O treated with 30 mL. 37% HCHO, the pH adjusted to 7.5 by KOH solution, the mixture left 6 h., and the pH adjusted to 7 by HCO₂H, and the mixture cooled to 4° gave 24 g. N,N’-methylenebis(thioisonicotinamide)-H₂O (VI), m. 146-7° (H₂O). VI was less active than the parent compound in tuberculosis in mice. The assignment of the linear structure was based on analyses and the fact that IR analyses gave none of the characteristic absorption bands for the triazine structure. Isonipecotamide (100 g.) in 450 g. POCl₃ refluxed 2 h. and concentrated in vacuo and poured on ice gave 37 g. 4-cyanopiperidine (VII), b₇ 100°, n²³_D 1.4741. VII (35 g.) left 48 h. at 25° in 300 mL. 30% NH₃ saturated with H₂S gave 30 g. thioisonipecotamide (VIII), m. 173-4° (H₂O). Attempts to convert the isonipecotamide to VIII using P₂S₅ failed with or without K₂S and only Va was obtained in 25-40% yields. Va (50 g.) and 56 g. α-bromopropionic acid heated 6 h. in PhMe gave 25 g. 5-methyl-2-(4-pyridyl)-4(5H)-thiazolone-HBr, m. above 250° (alc.). Va (50 g.) refluxed in 250 mL. AcCH₂Cl gave 11.5 g. 4-methyl-2-(4-pyridyl)thiazole-HCl, m. 219-20° (decomposition) (MeOH). Reduction of the C₅H₅N ring eliminated activity; N-oxidation reduced activity, and separation from the ring of the CSNH group eliminated activity as did also the conversion of the group into a ring system.

Journal of Organic Chemistry published new progress about 112401-09-9. 112401-09-9 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carbothioamide, and the molecular formula is C6H12N2S, Application of Piperidine-4-carbothioamide.

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

Shapiro, Seymour L. published the artcile3-Oxypiperidine derivatives, Formula: C7H15NO, the publication is Journal of the American Chemical Society (1959), 5146-9, database is CAplus.

cf. preceding abstract. The 3-oxypyridyl betaines and bis(3-oxypyridyl) betaines described in the preceding abstract hydrogenated over Rh-C yield the corresponding N-substituted-3-hydroxypiperidines and N,N’-bis(3-hydroxypiperidines), resp. These compounds, their ethers, and quaternary salts were examined for pharmacol. activity. N-(p-Chlorobenzyl)-3-oxypyridyl betaine-HCl (38.4 g.) in 250 cc. MeOH hydrogenated, 4 hrs. at 20° and 50 lb. initial pressure over 2 g. Rh-C, filtered, diluted with 300 cc. Et₂O, and the precipitate filtered off, the filtrate concentrated to 125 cc. and diluted with 260 cc. Et₂O, the precipitate filtered off, and the combined product (32.5 g.) recrystallized from MeOH-EtOAc yielded N-(p-chlorobenzyl)-3-hydroxypiperidine-HCl, m. 210-12°. Similarly were prepared the following compounds (m.p., % yield, and reduction time in hrs. given): 1-ethyl-3-hydroxypiperidine-HBr, 144-6° (EtOAc-Et₂O), 81, 1.75 [picrate, m. 81-3° (EtOAc-Et₂O)]; 1-benzyl-3-hydroxypiperidine-HCl, 167-70° (EtOH-EtOAc), 53, 4.5; 1-(2-dimethylaminoethyl)-3-hydroxypiperidine-2HCl, 267 8° (MeOH), 60, 1.5; 1-(3-dimethylaminopropyl)-3-hydroxypiperidine-2HCl (I), 222-6° (MeOH-EtOAc), 48. N-(5-Cyanopentyl)-3-oxypyridylbetaine-HCl (10.9 g.) in 200 cc. MeOH hydrogenated 9 hrs. over 2 g. Rh-C and filtered, the residue washed with 150 cc. H₂O, the MeOH removed from the combined filtrates, the aqueous residue basified with 6N NaOH, and the product isolated with CHCl₃ yielded 24% N-(6-aminohexyl)-3-hydroxypiperidine, b_0.08 110-12°, and 12% bis-[6-(3-hydroxypiperidino)hexyl]amine, b_0.2220-30°. 1-Phenacyl-3-oxypyridylbetaine-HCl(II)(40.8 g.) in 250 cc. MeOH hydrogenated over 2 g. Rh-C and worked up in the usual manner gave 5.0 g. distillate, b_0.09 90-5°, which deposited 0.4 g. 1-(2-phenethyl)-3-hydroxy-piperidine, m. 66-8° (hexane), and 22 g. 1-(2-hydroxy-2-phenylethyl)-3-hydroxypiperidine, b_0.05 140-50°. The p-Br derivative of II hydrogenated in the usual manner 16 hrs. yielded 8% 1-[2-(p-bromophenyl)-2-hydroxyethyl]-3-hydroxypiperidine (III), b_0.2 125-40°. The p-Cl derivative of II yielded similarly 6% p-Cl analog of III, m. 104-6° (heptane), and the p-Ph derivative of II gave 18% p-Ph (IIIa) analog of III, b_0.05 196-206°. The appropriate betaine hydrohalide (0.1 mole) in 250 cc. MeOH hydrogenated over 2 g. Rh-C gave the corresponding bis(3-hydroxypiperidino)alkane (m.p. or b.p./mm., % yield, and hydrogenation time in hrs. given): 1,3-bis(3-hydroxypiperidino)propane (IV), 146-51°/0.07, 50, 4, [dimethiodide m. 245-7° (EtOH)]; 1,4-butane analog (V) of IV, 108-10° (heptane), 60, 1, [V.2HCl, m. 263-5° (MeOH-EtOAc), 56%; V.2HBr, m. 261-5° (MeOH-EtOAc), 40%; V.2MeI, m. 235-7° (MeOH-EtOAc), 48%]; 1,5-pentane analog (VI) of IV, 176-80°/0.3, -, 6, (VI.2HBr, m. 173-5° (EtOH-EtOAc), 61%; VI.2MeI, m. 257-8° (EtOH), 73%); 1,6-hexane analog (VII) of IV, 91-3° (hexane), -, 5, [VII.2HBr, m. 219-21° (MeOH-EtOAc), 82%; VII.2MeI, m. 182-4° (EtOH), 71]; 1,4(1,4-dimethylbutane) analog, 162-8°/0.05, 59, 1.5; 1,10decane analog (VIII) of IV, 79-81° (pentane), -, 2, [VIII.-2HBr, 189-93° (MeOH-EtOAc), 33%; VIII.2MeI, m. 16575°]; p-CH₂C₆H₄CH₂ analog (IX) of IV, 140-3° (heptane), -, 7, [IX.2HCl, 309-10° (aqueous EtOH), 35%]. IV (3.9 g.) in 20 cc. C₅H₅N treated dropwise with stirring with 7.4 g. iso-PrCOCl during 0.5 hr., kept 20 hrs., and filtered, the residue dissolved in 15 cc. H₂O and 60 cc. Et₂O, the mixture adjusted to pH 8 with N NaOH and shaken, the aqueous phase extracted with 50 cc. Et₂O, and the combined Et₂O solutions worked up yielded 3.06 g. 1,3-bis(3-isobutyroxypiperidino)propane (X), b_0.03 156-8°. X (1.2 g.) in 8 cc. MeCN treated with 5 cc. p-MeC₆H₄SO₃Me, kept 10 days, and filtered yielded 0.2 g. X.2p-MeC₆H₄SO₃Me, m. 216-18° (MeOH). IV (10.5 g.) in 90 cc. PhMe treated at 50° with 2.54 g. NaH, refluxed 2 hrs. with stirring, the free base from 20.9 g. Me₂N-(CH₂)₂Cl.HCl in PhMe added, the mixture refluxed 20 hrs., cooled, and centrifuged, the supernatant decanted and evaporated, and the residue distilled yielded 7.86 g. 1,3-bis[3-(2-dimethylaminoethoxy)piperidino] propane, b_0.155 160-5°. VI.HBr (4.7 g.) in 49 cc. Ac₂O kept 6 days at 20°, the excess Ac₂O removed, the residue dissolved in 30 cc. Et₂O, the solution diluted with 15 cc. H₂O, adjusted with shaking with N NaOH to pH 8, the aqueous layer extracted with 25 cc. Et₂O, and the combined Et₂O solutions worked up yielded 1,5-bis(3-acetoxypiperidino)pentane (XI), b_0.05 158-64°. XI (177 mg.) in 5 cc. hexane treated with 1 cc. of a solution of 1.2 g. MeI in 10 cc. hexane, kept 4 days in the dark, and centrifuged, and the precipitate triturated with hexane gave XI.2MeI, hygroscopic, m. 108-13°. VIII (7.6 g.) in 100 cc. PhMe treated at 50° with 1.2 g. NaH, refluxed 2 hrs. with stirring, cooled, treated with 7.2 g. EtI, refluxed 3 hrs. with stirring, filtered, and distilled yielded 44% 1,10-bis(3-ethoxypiperidino)decane (XII), b_0.2 180-8°. N,N’-Tetramethylenebis(3oxypyridyl) betaine-2HCl (15.85 g.) in 250 cc. EtOH hydrogenated 9 hrs. over 0.5 g. PtO₂ and worked up in the usual manner yielded 4.5 g. 1,4-bis(piperidino)butane, b_0.05 114-20°, m. 107-10°; dipicrate, m. 189-90° (H₂O). N,N'(1,4-Buta-2-enylene)bis(3-oxypyridyl)betaine-2HBr hydrogenated 27 hrs. in the usual manner over PtO₂ and worked up gave 27 g. V, m. 108-12° (heptane). By the general procedures were prepared the following compounds XIII (R, Y, m.p./or b.p./mm., and % yield given): Ac, (CH₂)₃, 138-40°/0.05, 45; EtCO, (CH₂)₃ (XIV), 146-51°/0.03, 48; PrCO, (CH₂)₃, 156-62°/0.05, 57; Et, (CH₂)₃, 124°/0.02, 23; Ac, (CH₂)₄, 150-2°/0.02, 49; EtCO, (CH₂)₄ di-HCl salt, 270-5° (EtOH-hexane), 37; PrCO, (CH₂)₄, 170-4°/0.02, 58; iso-PrCO, (CH₂)₄, 156-62°/0.02, 34; Et, (CH₂)₄ (XV), 139-46°/0.1, 35; Me₂N(CH₂)₂, (CH₂)₄ (XVI), 148-65°/0.03, 21 [XVI.4MeI, m. 158-60° (EtOAc), 42%]; EtCO, (CH₂)₅ (XVII), 168-72°/0.04, 60; PrCO, (CH₂)₅ (XVIII), 177-84°/0.03, 550 iso-PrCO, (CH₂)₅, 178-88°/0.04, 50; Et, (CH₂)₅ (XIX), 140-50°/0.01, 34; Me₂N(CH₂)₂, (CH₂)₅, 168-75°/0.1, 34 [tetramethiodide, m. 250-4° (aqueous EtOH), 34%]; Ac, (CH₂)₆, 67-9° (aqueous Me₂CO), 8; EtCO, (CH₂)₆, 176-82°/0.03, 53; PrCO, 188-90°/0.03, 56; iso-PrCO, 180-5°/0.02, 88; p-O₂NC₆H₄CO, (CH₂)₆ dipicrate, 224-5° (BuOH), -; Et, (CH₂)₆ (XX), 150-8°/0.08, 29; Me₂NCH₂CH₂, (CH₂)₆ (XXI), 186-90°/0.16, 16 [XII.4MeI, m. 258-61° (MeOH-EtOAc), 20%]; Ac, CHMe(CH₂)₂CHMe (XXII), 158-62°/0.03, 81; Ac, (CH₂)₁₀, 76-8° (aqueous MeOH), 24; EtCO, (CH₂)₁₀ (XXIII), 196-204°/0.03, 64; PrCO, (CH₂)₁₀ (XXIV), 208-10°/0.08, 28 [XXIV.2p-MeC₆H₄SO₃Me, m. 125-7° (BuOH), 6%]; iso-PrCO, (CH₂)₁₀ (XXV), 198-208°/0.02, 34. Potentiated adrenaline activity was shown by I, IIIa, XIV, V.2HCl, XV, VI.2HBr, VI.2MeI, VII.2MeI, VIII.2HBr, moderate ganglionic blocking action by XVIII, partial block by IIIa, V.HCl, and XVI, adrenergic blocking effect by XXI and VIII.2HBr, and slight, lasting hypotensive effect by IIIa, V.HCl, XVI, and XIX. IIIa, LD_min. 750 mg./kg. subcutaneously, at 20 mg./kg. reduced the motor activity of rats 43%. XXI.4MeI showed depression of motor activity. Antiinflammatory activity of 17 units/g. was obtained with XII; XX, XXII, VI.2HBr, IV.2MeI, XV, XI, XVII, XIX showed lesser effectiveness. Curare-like effects (about 10% of the activity of decamethonium) were noted with XXI, XXIII, XXIV, XXV, and XII.

Journal of the American Chemical Society 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 C25H23NO4, Formula: C7H15NO.

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