Heterocyclic Building Blocks-piperidine

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

Crich, David published the artcileSynthesis and Glycosylation of a Series of 6-Mono-, Di-, and Trifluoro S-Phenyl 2,3,4-Tri-O-benzyl-thiorhamnopyranosides. Effect of the Fluorine Substituents on Glycosylation Stereoselectivity, SDS of cas: 4972-31-0, the publication is Journal of the American Chemical Society (2007), 129(38), 11756-11765, database is CAplus and MEDLINE.

A series of 6-mono-, di-, and trifluoro analogs of S-Ph 2,3,4-tri-O-benzyl-D– or L-thiorhamnopyranoside has been synthesized and used as donors in glycosylation reactions, with activation by the 1-benzene-sulfinyl piperidine/triflic anhydride system. The stereochem. outcome of the glycosylation reactions was found to depend on the electron-withdrawing capability of the disarming substituent at the 6-position, i.e., on the number of fluorine atoms present. The results are explained with regard to the increased stability of the glycosyl triflates, shown to be intermediates in the reaction by low-temperature ¹H NMR experiments, with increased fluorine content.

Journal of the American Chemical Society 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, SDS of cas: 4972-31-0.

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

Crich, David published the artcileThe 3,4-O-Carbonate Protecting Group as a β-Directing Group in Rhamnopyranosylation in Both Homogeneous and Heterogeneous Glycosylations As Compared to the Chameleon-like 2,3-O-Carbonates, SDS of cas: 4972-31-0, the publication is Journal of Organic Chemistry (2003), 68(22), 8453-8458, database is CAplus and MEDLINE.

It is demonstrated that the β-selectivity observed in the insoluble silver salt mediated couplings of 2,3-O-carbonate-protected rhamnosyl bromides is uniquely due to the heterogeneous nature of the reaction. In homogeneous solution these same donors are α-selective, a fact that is attributed to the half-chair conformation of these substances which reduces the energy barrier to oxacarbenium ion formation. It is suggested that the 2,3-O-carbonate group be dubbed torsionally arming in the manno- and rhamnopyranose series. When the carbonate group is removed to the 3,4-O-position a β-selective system is formed, in both homogeneous and heterogeneous conditions, and it is demonstrated that this selectivity arises from the combination of the electron-withdrawing nature of the carbonate and its inability to take part in neighboring participation.

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

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

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

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

Ouach, Aziz published the artcileBis(het)aryl-1,2,3-triazole quinuclidines as α7 nicotinic acetylcholine receptor ligands: Synthesis, structure affinity relationships, agonism activity, [¹⁸F]-radiolabeling and PET study in rats, Recommanded Product: 1-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperidine, the publication is European Journal of Medicinal Chemistry (2019), 449-469, database is CAplus and MEDLINE.

In this paper we describe the design and synthesis of bis(Het)Aryl-1,2,3-triazole quinuclidine α7R ligands using an efficient three-step sequence including a Suzuki-Miyaura cross coupling reaction with com. available and home-made boron derivatives The exploration of SAR required the preparation of uncommon boron derivatives Forty final drugs were tested for their ability to bind the target and nine of them exhibited Ki values below nanomolar concentrations The best scores were always obtained when the 5-phenyl-2-thiophenyl core was attached to the triazole. The selectivity of these compounds towards the nicotinic α4β2 and serotoninergic 5HT3 receptors was assessed and their brain penetration was quantified by the preparation and in vivo evaluation of two [¹⁸F] radiolabeled derivatives It can be expected from our results that some of these compounds will be suitable for further developments and will have effects on cognitive disorders.

European Journal of Medicinal Chemistry published new progress about 859833-21-9. 859833-21-9 belongs to piperidines, auxiliary class Piperidine,Boronic acid and ester,Benzene,Boronic Acids,Boronate Esters, name is 1-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperidine, and the molecular formula is C18H28BNO2, Recommanded Product: 1-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperidine.

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

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

Miller, Shelli A. published the artcileProbing the Effect of Counterions on the Oxidation of Alcohols Using Oxoammonium Salts, Computed Properties of 219543-09-6, the publication is European Journal of Organic Chemistry (2020), 2020(1), 108-112, database is CAplus.

The effect of varying the counterion in the oxoammonium salt mediated oxidation of alcs. has been probed. Computational and exptl. results suggest that the counterion is non-innocent in oxoammonium salt mediated oxidations and the outcome of the reaction is related, at least in part, to the ability of the hydrogen-bond accepting nature of the anion.

European Journal of Organic Chemistry 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, Computed Properties of 219543-09-6.

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