Heterocyclic Building Blocks-piperidine

Paul, Raymond published the artcileA new synthesis of N-substituted 3-hydroxypiperidines, Formula: C7H15NO, the publication is Compt. rend. (1945), 560-2, database is CAplus.

When a mono-alkyl- or aryltetrahydrofurfurylamine (I) is treated with 2 mols. of HBr, the ring is apparently opened and the intermediate haloamino alc. is converted to the corresponding alkyl- or aryl-3-hydroxypiperidine (II) by the action of heat and alkali. Various I were made in 2 ways: (1) by heating tetrahydrofurfuryl chloride with a large excess of primary amine at 100° for 10 h.; (2) by hydrogenation at 100°, with Raney Ni, of 1 mol. of furfural and 1 mol. of primary amine in alc. The data for the I are given below in the order b.p., d₄, n_D, and m.p. of picrate: alkyl = Me 155-6° (b₉ 40°), 0.928/21.5°, 1.4436/21.5°, 129°; Et 170-1° (b₁₂ 62°), 0.913/21°, 1.4430/21°, 98°; Pr b₁₀ 69°; Ph b₉ 154°, 1.071/21°, 1.5617/21°, 117°; benzyl b₁₁ 151°, 1.024/21°, 1.5240/21°, 135°; 3-pyridyl, b₆ 160-1°, 1.172/23°, 1.5950/23°, 161°. One mol. I is treated with 2 mols. dry HBr and warmed at 100° for 3 h. A little water is added and the solution neutralized carefully with NH₃. The Me and Et derivatives of II are salted out with K₂CO₃, the others sep. first as oils, which on treatment with concentrated KOH give II. They are colorless, very soluble in water, strongly alk. Data for derivatives of II are given in the order b.p., d₄, n_D, m.p. of HCl salt of benzoate ester; alkyl = Me b₁₆ 79°, 0.9635/16°, 1.4695/16°, 194°; Et b₁₆ 93°, 0.9580/14°, 1.4769/14°, 204°; Pr b₁₅ 77°, 0.971/15°, 1.4589/15°, 176°; Ph b₂ 145-146°, 1.092/21°, 1.5756/21°, oily, 141° (m.p. picrate); benzyl b₁₂ 155-156, 1.056/16°, 1.5402/16°, oily. The Et and Ph derivatives are identical with those found earlier. Unsubstituted I could not be converted into unsubstituted II.

Compt. rend. 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, Formula: C7H15NO.

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

Ledneczki, Istvan published the artcileDiscovery of novel steroidal histamine H₃ receptor antagonists/inverse agonists, Application In Synthesis of 39546-32-2, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(19), 4525-4530, database is CAplus and MEDLINE.

Emerging from an HTS campaign, novel steroid-based histamine H₃ receptor antagonists were identified and characterized. Structural moieties of the hit compounds were combined to improve binding affinities which resulted in compound I as lead mol. During the lead optimization due to the versatile modifications of diamino steroid derivatives, several in vitro potent compounds with subnanomolar binding affinities to histamine H₃ receptors were found. The unfavorable binding to rat muscarinic receptors was successfully reduced by tuning the basicity. Compound II showed significant in vivo activity in the rat dipsogenia model and could serve as a pharmacol. tool in the future.

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, Application In Synthesis of 39546-32-2.

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

Nojiri, Masutoshi published the artcileCharacterization of an enantioselective amidase from Cupriavidus sp. KNK-J915 (FERM BP-10739) useful for enzymatic resolution of racemic 3-piperidinecarboxamide, Synthetic Route of 39546-32-2, the publication is Journal of Molecular Catalysis B: Enzymatic (2014), 136-142, database is CAplus.

A novel amidase (CsAM) acting on (R,S)-N-benzyl-3-piperidinecarboxamide was purified from Cupriavidus sp. KNK-J915 (FERM BP-10739) and characterized. The enzyme acts on (R,S)-N-benzyl-3-piperidinecarboxamide S-selectively to yield (R)-N-benzyl-3-piperidinecarboxamide. Anal. gel filtration column chromatog. and SDS-PAGE revealed that the enzyme is a tetramer with a subunit of approx. 47 kDa. It has a broad substrate spectrum against nitrogen-containing heterocyclic amides. Its optimal pH and temperature are 8.0-9.0 and 50 °C, resp. The CsAM gene was cloned and sequenced, and it was found to comprise 1341 bp and encode a polypeptide of 46,388 Da. The deduced amino acid sequence exhibited 78% identity to that of a putative amidase (CnAM) from Cupriavidus necator JMP134. The cultured cells of recombinant Escherichia coli producing CnAM could be used for the S-selective hydrolysis of (R,S)-N-benzyl-3-piperidinecarboxamide but could not be used for the S-selective hydrolysis of (R,S)-3-piperidinecarboxamide because of its very low level of selectivity. In contrast, the cultured cells of recombinant E. coli producing CsAM could hydrolyze both (R,S)-N-benzyl-3-piperidinecarboxamide and (R,S)-3-piperidinecarboxamide with high S-selectivity.

Journal of Molecular Catalysis B: Enzymatic 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

Son, Sang-Hyun published the artcilePre-activation of fully acetylated dodecyl thioglycosides with BSP-Tf₂O led to efficient glycosylation at low temperature, HPLC of Formula: 4972-31-0, the publication is Carbohydrate Research (2009), 344(3), 285-290, database is CAplus and MEDLINE.

Fully acetylated dodecyl thioglycosides were found to be useful as glycosyl donors by activation with 1-benzenesulfinyl piperidine (BSP) and triflic anhydride (Tf₂O) at -78 °C. The glycosyl acceptor was added to the reaction mixture at the same temperature to furnish various disaccharide, including the protected Lewis a (Le^a) trisaccharide, in good yields.

Carbohydrate Research 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 C8H11NO, HPLC of Formula: 4972-31-0.

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

Son, Sang-Hyun published the artcileStereoselective tris-glycosylation to introduce β-(1→3)-branches into gentiotetraose for the concise synthesis of phytoalexin-elicitor heptaglucoside, Application of 1-(Phenylsulfinyl)piperidine, the publication is Organic & Biomolecular Chemistry (2008), 6(8), 1441-1449, database is CAplus and MEDLINE.

Dodecyl thioglycosides (3, 4, 5) were prepared by conventional transformation of d-glucose and used as new glycosyl donors for a short-step synthesis of phytoalexin elicitor heptaglucoside. A gentio-tetraoside derivative (6) having three hydroxyl groups was synthesized by NIS-TfOH promoted glycosylate in more than 90% yield followed by selective removal of temporary protective groups. Undesired formation of α-glycosides at the introduction of β-(1→3)-branches into gentio-oligosaccharides was found to be suppressed by use of a thiophilic reagent system, BSP (1-benzenesulfinyl piperidine)-Tf₂O, giving the heptaglucoside in only four glycosylation steps.

Organic & Biomolecular 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 C28H18O4, Application of 1-(Phenylsulfinyl)piperidine.

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

Yang, Shyh-Ming published the artcile4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: Urea-based analogs, SDS of cas: 1032229-33-6, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(24), 6773-6776, database is CAplus and MEDLINE.

A new series of urea-based, 4-bicyclic heteroaryl-piperidine derivatives as potent SCD1 inhibitors is described. The structure-activity relationships focused on bicyclic heteroarenes and aminothiazole-urea portions are discussed. A trend of dose-dependent decrease in body weight gain in diet-induced obese (DIO) mice is also demonstrated.

Bioorganic & Medicinal Chemistry Letters 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 C14H14, SDS of cas: 1032229-33-6.

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

Dai, Liang published the artcileGut Microbiota and Related Metabolites Were Disturbed in Ulcerative Colitis and Partly Restored After Mesalamine Treatment, Category: piperidines, the publication is Frontiers in Pharmacology (2020), 620724, database is CAplus and MEDLINE.

Mesalamine has been well used in the improvement of ulcerative colitis (UC) in clinics, however, the underlying mechanisms were not well illustrated. To explore its efficacy from the perspective of gut microbiota and related metabolites, we employed 16S rRNA sequencing and metabolomics approaches in stool samples across 14 normal healthy controls (NC group), 10 treatment-naïve UC patients (UC group) and 14 UC patients responded to mesalamine treatment (mesalamine group). We noted that the gut microbiota diversity and community composition were remarkably perturbed in UC group and partially restored by mesalamine treatment. The relative abundance of 192 taxa in genus level were significantly changed in UC group, and 168 genera were significantly altered after mesalamine intervention. Meanwhile, a total of 127 metabolites were significantly changed in UC group and 129 metabolites were significantly altered after mesalamine treatment. Importantly, we observed that many candidates including 49 genera (such as Escherichia-shigella, Enterococcus and Butyricicoccus) and 102 metatoblites (such as isoleucine, cholic acid and deoxycholic acid) were reversed by mesalamine. Spearman correlation anal. revealed that most of the candidates were significantly correlated with Mayo score of UC, and the relative abundance of specific genera were significant correlated with the perturbation of metabolites. Pathway anal. demonstrated that genera and metabolites candidates were enriched in many similar mol. pathways such as amino acid metabolism and secondary metabolites biosynthesis. Importantly, ROC curve anal. identified a gut microbiota signature composed of five genera including Escherichia-Shigella, Streptococcus, Megamonas, Prevotella_9 and [Eubacterium] _coprostanoligenes _group which might be used to distinguish UC group from both NC and mesalamine group. In all, our results suggested that mesalamine might exert a beneficial role in UC by modulating gut microbiota signature with correlated metabolites in different pathways, which may provide a basis for developing novel candidate biomarkers and therapeutic targets of UC.

Frontiers in Pharmacology published new progress about 826-36-8. 826-36-8 belongs to piperidines, auxiliary class Natural product, name is 2,2,6,6-Tetramethylpiperidin-4-one, and the molecular formula is C9H17NO, Category: piperidines.

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

Ito, Masahiro published the artcileDiscovery of 3-Benzyl-1-(trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors, Safety of (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, the publication is Journal of Medicinal Chemistry (2018), 61(17), 7710-7728, database is CAplus and MEDLINE.

Cyclin-dependent kinase 12 (CDK12) plays a key role in the coordination of transcription with elongation and mRNA processing. CDK12 mutations found in tumors and CDK12 inhibition sensitize cancer cells to DNA-damaging reagents and DNA-repair inhibitors. This suggests that CDK12 inhibitors are potential therapeutics for cancer that may cause synthetic lethality. Here, we report the discovery of 3-benzyl-1-(trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea derivatives as novel and selective CDK12 inhibitors. Structure-activity relationship studies of a HTS hit, structure-based drug design, and conformation-oriented design using the Cambridge Structural Database afforded the optimized compound 2, which exhibited not only potent CDK12 (and CDK13) inhibitory activity and excellent selectivity but also good physicochem. properties. Furthermore, 2 inhibited the phosphorylation of Ser2 in the C-terminal domain of RNA polymerase II and induced growth inhibition in SK-BR-3 cells. Therefore, 2 represents an excellent chem. probe for functional studies of CDK12 and could be a promising lead compound for drug discovery.

Journal of Medicinal Chemistry 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, Safety of (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.

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

Yamada, Takeshi published the artcileDialkyl-phosphates as stereo-directing protecting groups in oligosaccharide synthesis, Category: piperidines, the publication is Angewandte Chemie, International Edition (2006), 45(45), 7575-7578, database is CAplus and MEDLINE.

Double duty: A phosphoric ester at the C2 position in glycosyl donors directs the glycosylation to occur selectively at the anomeric carbon atom with complete 1,2-trans selectivity. Since the phosphoric ester can be removed to give the hydroxy function, this group serves as a stereo-directing protecting group in oligosaccharide synthesis.

Angewandte Chemie, International Edition 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 C7H8BBrO3, Category: piperidines.

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

Clapham, Bruce published the artcileUse of a scintillant-containing macroporous resin in both solid phase synthesis and subsequent on-bead scintillation-based analysis, Related Products of piperidines, the publication is Tetrahedron Letters (2000), 41(13), 2257-2260, database is CAplus.

A chem.-functionalized scintillant-containing divinylbenzene-2,5-diphenyl-4-vinyloxazole-4-ethylstyrene-4-vinylbenzyl chloride copolymer macroporous resin was used successfully in a two stage solid phase organic synthesis. The second step in this synthesis involved the covalent attachment of a tritiated acetate group to the resin. The resultant radiolabeled scintillant-containing resin beads scintillate spontaneously and with high efficiency due to the close proximity of the tritium atoms to the scintillant mols. within the beads.

Tetrahedron Letters published new progress about 35661-58-6. 35661-58-6 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-((9H-Fluoren-9-yl)methyl)piperidine, and the molecular formula is C19H21N, Related Products of piperidines.

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