Tag: M.W=100-150

Dong, Yuxiang published the artcileStructure-Activity Relationship of the Antimalarial Ozonide Artefenomel (OZ439), Quality Control of 39546-32-2, the publication is Journal of Medicinal Chemistry (2017), 60(7), 2654-2668, database is CAplus and MEDLINE.

Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with their higher pK_a and lower log D_7.4 values. For primary amino ozonides, addition of polar functional groups decreased in vivo antimalarial efficacy. For secondary amino ozonides, addnl. functional groups had variable effects on metabolic stability and efficacy, but the most effective members of this series also had the highest log D_7.4 values. For tertiary amino ozonides, addition of polar functional groups with H-bond donors increased metabolic stability but decreased in vivo antimalarial efficacy. Primary and tertiary amino ozonides with cycloalkyl and heterocycle substructures were superior to their acyclic counterparts. The high curative efficacy of these ozonides was most often associated with high and prolonged plasma exposure, but exposure on its own did not explain the presence or absence of either curative efficacy or in vivo toxicity.

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

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

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

Keita, Massaba published the artcileSynthesis of isocyanides through dehydration of formamides using XtalFluor-E, Synthetic Route of 39546-32-2, the publication is Tetrahedron Letters (2015), 56(2), 461-464, database is CAplus.

The formation of isocyanides from formamides using XtalFluor-E, [Et₂NSF₂]BF₄, is presented. A wide range of formamides can be used to produce the corresponding isocyanides in up to 99% yield. In a number of cases, the crude products showed good purity (generally >80% by NMR) allowing to be used directly in multi-component reactions.

Tetrahedron 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, Synthetic Route of 39546-32-2.

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

Decara, Juan M. published the artcileDiscovery of V-0219: A Small-Molecule Positive Allosteric Modulator of the Glucagon-Like Peptide-1 Receptor toward Oral Treatment for “Diabesity”, Quality Control of 39546-32-2, the publication is Journal of Medicinal Chemistry (2022), 65(7), 5449-5461, database is CAplus and MEDLINE.

Peptidic agonists of the glucagon-like peptide-1 receptor (GLP-1R) have gained a prominent role in the therapy of type-2 diabetes and are being considered for reducing food intake in obesity. Potential advantages of small mols. acting as pos. allosteric modulators (PAMs) of GLP-1R, including oral administration and reduced unwanted effects, could improve the utility of this class of drugs. Here, we describe the discovery of compound 9 (4-{[1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-3-yl]methyl}morpholine, V-0219) that exhibits enhanced efficacy of GLP-1R stimulation, subnanomolar potency in the potentiation of insulin secretion, and no significant off-target activities. The identified GLP-1R PAM shows a remarkable in vivo activity, reducing food intake and improving glucose handling in normal and diabetic rodents. Enantioselective synthesis revealed oral efficacy for (S)-9 in animal models. Compound 9 behavior bolsters the interest of a small-mol. PAM of GLP-1R as a promising therapeutic approach for the increasingly prevalent obesity-associated diabetes.

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

Giannini, Giuseppe published the artcileST7612AA1, a Thioacetate-ω(γ-lactam carboxamide) Derivative Selected from a Novel Generation of Oral HDAC Inhibitors, Quality Control of 72002-30-3, the publication is Journal of Medicinal Chemistry (2014), 57(20), 8358-8377, database is CAplus and MEDLINE.

A systematic study of medicinal chem. aimed at identifying a new generation of HDAC inhibitors, through the introduction of a thiol zinc-binding group and of an amide-lactam in the ω-position of the polyethylene chain of the vorinostat scaffold, allowed the selection of a new class of potent pan-HDAC inhibitors (pan-HDACis). Simple, highly versatile, and efficient synthetic approaches were used to synthesize a library of these new derivatives, which were then submitted to a screening for HDAC inhibition as well as to a preliminary in vitro assessment of their antiproliferative activity. Mol. docking into HDAC crystal structures suggested a binding mode for these thiol derivatives consistent with the stereoselectivity observed upon insertion of amide-lactam substituents in the ω-position. ST7612AA1 I, selected as a drug candidate for further development, showed an in vitro activity in the nanomolar range associated with a remarkable in vivo antitumor activity, highly competitive with the most potent HDAC inhibitors, currently under clin. trials. A preliminary study of PK and metabolism is also illustrated.

Journal of Medicinal Chemistry published new progress about 72002-30-3. 72002-30-3 belongs to piperidines, auxiliary class Piperidine,Chiral,Carboxylic acid,Amide, name is (R)-6-Oxopiperidine-2-carboxylic acid, and the molecular formula is C6H9NO3, Quality Control of 72002-30-3.

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

Pettenuzzo, Andrea published the artcileDesign, physico-chemical characterization and in vitro biological activity of organogold(III) glycoconjugates, SDS of cas: 39546-32-2, the publication is Dalton Transactions (2021), 50(25), 8963-8979, database is CAplus and MEDLINE.

To develop new metal-based glycoconjugates as potential anticancer agents, four organometallic Au(III)-dithiocarbamato glycoconjugates [Au(III)(2-Bnpy)(SSC-Inp-GlcN)](PF₆) (2-Bnpy: 2-benzylpyridine; Inp: isonipecotic moiety; GlcN: amino-glucose scaffold; Au3-Au6) and the corresponding model nonglycosylated counterparts [Au(III)(2-Bnpy)(SSC-Inp-R)](PF₆) (R: OEt (Au1), NH₂ (Au2)) were generated and characterized by several anal. techniques (elemental anal., FTIR, ¹H-/¹³C-NMR, ESI-MS, UV-visible, x-ray crystallog.). Their stability under physiol.-relevant conditions (PBS solution) and n-octanol/PBS distribution coefficient (D_7.4) also were evaluated. Au(III) glycoconjugates showed an antiproliferative effect against ovarian carcinoma A2780 cells, with GI₅₀ values in the low micromolar range. Remarkably, their cell growth inhibitory effect increases upon the addition of a glucose transporter 1 (GLUT1) inhibitor, thus ruling out the involvement of GLUT1 in their transport inside the cell. Addnl. mechanistic studies were carried out in A2780 cells, supporting the hypothesis of a facilitated diffusion mechanism (possibly mediated by glucose transporters other than GLUT1), and revealing their capability to act as topoisomerase I and II inhibitors and to disrupt mitochondrial membrane integrity, giving ROS, thus resulting in the promotion of oxidative stress and, eventually, cell death.

Dalton Transactions 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, SDS of cas: 39546-32-2.

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

Bartmann, K. published the artcileCan the experimental guinea-pig tuberculosis be influenced by a Azorhodanid H depot treatment?, Safety of 1-Ethylpiperidin-3-ol, the publication is Beitraege zur Klinik der Tuberkulose und Spezifischen Tuberkulose-Forschung (1955), 75-8, database is CAplus.

Azorhodanid H in the dose used (weekly 30 mg. as suspension subcutaneously) barely influences the course of guinea-pig tuberculosis, while a lower but still optimal isoniazid treatment of the animals (5 mg./kg. for 4 weeks and further for 9.5 weeks twice weekly) practically completely prevented lymphogenous and hematogenous spread.

Beitraege zur Klinik der Tuberkulose und Spezifischen Tuberkulose-Forschung 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, Safety of 1-Ethylpiperidin-3-ol.

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

Mikhlina, E. E. published the artcileSynthesis of 3- and 4-hydroxypiperidine derivatives, Related Products of piperidines, the publication is Zhurnal Obshchei Khimii (1960), 1885-93, database is CAplus.

cf. CA 54, 22632h. Refluxing 1-ethyl-3-hydroxypiperidine with p-ClC₆H₄COCl in C₆H₆ gave 62.5% 1-ethyl-3-(p-chlorobenzoxy)piperidine-HCl, m. 185-7°. Similarly were prepared 68-93% yields of HCl salts of the corresponding: acetate, m. 179-81°; propionate, m. 174-5°; p-nitrobenzoate, m. 175-7°; phenoxyacetate, m. 160-2°; and cinnamate, m. 164-6°. 4-Piperidone-HCl with NaBH₄ in EtOH with ice cooling gave in 20 h. 61% 4-hydroxypiperidine, b₁₃ 106°. Similarly was prepared 83.5% 1-methyl-4-hydroxypiperidine, b₁₂ 94°, and 84.5% 1-ethyl-4-hydroxypiperidine, b₅ 91°. 1-Ethyl-3-hydroxypiperidine with CH₂:CHCN in dioxane-MeOH in the presence of 30% KOH in MeOH gave in 4 h. at 65° 80.2% 1-ethyl-3-(2-cyanoethoxy)piperidine (I), b₃ 125-6°. Similarly were prepared 80% 1-methyl-4-(2-cyanoethoxy)piperidine, b₇ 125-6°, n¹⁷_D 1.4668, and 1-Et analog, b₄ 122°. I and dry HCl in refluxing EtOH 4 h. gave 66.6% 1-ethyl-3-(2-carbethoxyethoxy)piperidine (II), b₃ 120-1°, n¹⁷_D 1.4589, also formed by the use of EtOH-H₂SO₄ in 18 h. at reflux. Similarly were prepared 48% 1-methyl-4-(2-carbethoxyethoxy)piperidine, b₂ 102°, n¹⁸_D 1.4558, and 66% 1-ethyl-4-(2-carbethoxyethoxy)piperidine, b₄ 113°. II with LiAlH₄ in Et₂O gave 86.8% 1-ethyl-3-(γ-hydroxypropoxy)piperidine (III), b₃ 116-18°, n¹⁷_D 1.4749. Similarly were prepared 76.3% 1-methyl-4-(γ-hydroxypropyl)piperidine, b₄ 114-16°, n¹⁷_D 1.4741, and 88% 1-Et analog, b₅ 125°, n²⁴_D 1.4713. III treated with EtOH-HCl, evaporated, and treated with SOCl₂ in MePh gave after aqueous treatment 1-ethyl-3-(γ-chloropropoxy)piperidine, which refluxed 6 h. with thiourea in N HCl then heated with aqueous NaOH 0.5 h. gave 71.4% 1-ethyl-3-(γ-mercaptopropoxy)piperidine, b₈ 132-3°. Similarly was prepared 71% 1-methyl-4-(γ-mercaptopropoxy)piperidine (IV), b_0.7 100°, and 57.2% 1-ethyl-4-(γ-mercaptopropoxy)piperidine, b₁ 110°. III treated with SOCl₂ in hot C₆H₆ 3 h. at 65°, evaporated, and made alk. with K₂CO₃ gave crude 1-ethyl-3-(γ-chloropropoxy)piperidine, which treated with thiourea in aqueous EtOH 6 h. gave 43.2% bis[γ-(1-ethyl-3-piperidyloxy)propyl] sulfide, b_0.5 202-7°. Heating 1-methyl-4-(γ-hydroxypropoxy)piperidine with AcCl in C₆H₆ 6 h. gave 94% 1-methyl-4-(γ-acetoxypropoxy)piperidine, b₃ 111°; methiodide m. 77-9°. IV with BzCl in Et₂O gave 91% 1-methyl-4-(γ-benzoylthiopropoxy)piperidine-HCl, m. 129.5-30°. Similarly were prepared the following 1-ethyl-3-(γ-acyloxypropoxy)piperidines (acyl group shown): propionate, b₁ 125-7°; benzoate, b₁ 190-2°; p-nitrobenzoate, b₁ 201-3°; and pyridylcarbonyl, b_0.6 177-8°. Also reported was 1-ethyl-3-(γ-acetylthiopropoxy)piperidine, b_0.75 135°. The following 1-alkyl-4-[γ-acyloxy(or acylthio)propoxy] piperidines were reported (alkyl and acyl groups shown, resp.): Me, benzoxy, b₃ 170-1° (HCl salt m. 120°); Me, p-nitrobenzoylthio (HCl salt m. 127-8°); Me, p-chlorobenzoylthio (HCl salt m. 127-31°; Me, acetylthio, b_0.5 107-10°; Me, diphenylacetylthio (HCl salt m. 57-7.5°); Et, acetoxy, b_0.5 97°; Et, benzoxy, b_0.5 155-61°; Et, diphenylacetoxy, b_0.7 203-5°; Et, acetylthio (HCl salt m. 68°); Et, benzoylthio (HCl salt m. 124-5°); Et, phenylacetylthio (HCl salt m. 95-7°); Et, diphenylacetylthio (HCl salt m. 103-7°); Bu, benzoylthio (HCl salt m. 115-18°); Bu, acetylthio (HCl salt m. 102-3°). Acrylonitrile with 4-hydroxypiperidine in the presence of KOH in MeOH-dioxane gave 74.5% 4-(2-cyanoethoxy)piperidine, b₂ 135°, n¹⁴_D 1.4630, which with HCl-EtOH at reflux gave 65.5% 4-(2-carbethoxyethoxy)piperidine, b₄ 122°. This in pyridine treated with PrCOCl 4 h. at 65°, the crude product after aqueous treatment neutralized with K₂CO₃, extracted with C₆H₆, and reduced with LiAlH₄ gave 56% 1-butyl-4-(γ-hydroxypropoxy)piperidine, b_0.5 130-2°.

Zhurnal Obshchei Khimii 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, Related Products of piperidines.

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

Doyle, F. P. published the artcileChemistry and pharmacology of some esters derived from basic alcohols, Safety of 1-Ethylpiperidin-3-ol, the publication is Journal of Medicinal Chemistry (1965), 8(5), 571-6, database is CAplus.

The preparation of a number of α-alkoxy-α,α-diphenylacetates derived from open-chain basic alcs. is described. Some of these compounds possess antitussive activity comparable to that of codeine phosphate and of the same order as that of their analogs which contain pyrrolidine or piperidine rings. 2-Diethylamino-1-(α-methoxy-α,α-diphenylacetoxy)propane rearranged on heating to 1-diethylamino-2-(α-methoxy-α,α-diphenylacetoxy)propane.

Journal of Medicinal Chemistry 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, Safety of 1-Ethylpiperidin-3-ol.

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