Tag: M.W=100-150

Dmitriev, L. B. published the artcileDemyanov reaction with 1-methyl-3-aminomethylpiperidine, Safety of (1-Methylpiperidin-3-yl)methanamine, the publication is Izvestiya Timiryazevskoi Sel’skokhozyaistvennoi Akademii (1968), 195-200, database is CAplus.

A solution of 5.1 g. 1-methyl-3-aminomethylpiperidine in 50 ml. H2O was neutralized with 10% H3PO4 to pH 5.5 and a solution of 4.2 g. NaNo2 in 50 ml. H2O added dropwise at 0-5°, the mixture kept 2 hrs. at 0-5° and overnight at room temperature, heated at 70° until all gas bubbles were eliminated, and worked up to give 8% Demyanov rearrangement products I-IV, but mainly V-IX. The influence of various temperatures and pH values on the direction of the reaction was not significant.

Izvestiya Timiryazevskoi Sel’skokhozyaistvennoi Akademii 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, Safety of (1-Methylpiperidin-3-yl)methanamine.

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

Wu, Yong-Jin published the artcileDevelopment of New Benzenesulfonamides As Potent and Selective Na_v1.7 Inhibitors for the Treatment of Pain, Computed Properties of 14613-37-7, the publication is Journal of Medicinal Chemistry (2017), 60(6), 2513-2525, database is CAplus and MEDLINE.

By taking advantage of certain features in piperidine (I), the authors developed a novel series of cyclohexylamine- and piperidine-based benzenesulfonamides as potent and selective Na_v1.7 inhibitors. However, 4-((((1S,4S)-4-aminocydohexyl)methyl)amino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide (24), one of the early analogs, failed to reduce phase 2 flinching in the mouse formalin test even at a dose of 100 mpk PO due to insufficient DRG exposure attributed to poor membrane permeability. Two analogs with improved membrane permeability showed much increased DRG concentrations at doses of 30 mpk PO but, confoundingly, only one of these was effective in the formalin test. More data are needed to understand the disconnect between efficacy and exposure relationships.

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 C12H10FeO4, Computed Properties of 14613-37-7.

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

Han, Si-yin published the artcileMaillard reaction of sisal hemp juice hydrolysate and its volatile composition, Recommanded Product: 1-Ethylpiperidin-3-ol, the publication is Shipin Gongye (Shanghai, China) (2014), 35(3), 14-17, database is CAplus.

Sisal hemp juice was hydrolyzed by muriatic acid, hydrolyzate obtained from that would have Maillard reaction, and volatile components of the Maillard reaction products were detected. A hydrolysis of sisal hemp juice by muriatic acid 6 mol/L, volume ratio of muriatic acid and sisal juice 4:1 and hydrolysis in 100 °C for 14 h leaded to a degree hydrolysis of 16.8%. The highest browning degree was measured in the hydrolyzate at pH 7 after incubation in 100 °C for 30 min. Under this condition the volatile components of these Maillard reaction products mainly included 8 categories via the detection of GC-MS, which were alc., aldehyde, ketone, acid, ester, phenol, alkene and furan, and it can be developed as a natural fumette for tobacco.

Shipin Gongye (Shanghai, China) 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, Recommanded Product: 1-Ethylpiperidin-3-ol.

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

Wu, Ting-Ting published the artcileDesign, synthesis and bioevaluation of novel substituted triazines as potential dual PI3K/mTOR inhibitors, Application In Synthesis of 39546-32-2, the publication is European Journal of Medicinal Chemistry (2020), 112637, database is CAplus and MEDLINE.

A series of novel substituted triazines bearing a benzimidazole scaffold I [R = morpholino, 4-methylpiperazin-1-yl, ((1S)-2-amino-1-methyl-2-oxo-ethyl)amino, etc.] were designed and synthesized based on the structures of known anti-cancer agents, namely gedatolisib and alpelisib. All the target compounds were screened for inhibitory activity against PI3Kα and mTOR kinases. Notably, most analogs exhibited IC₅₀ in the nanomolar range. Investigation of the isoenzyme selectivity indicated that the compounds exhibited remarkable inhibitory activity against PI3Kδ, especially compound I [R = 4-carbamoyl-1-piperidyl] showed an IC₅₀ value of 2.3 nM for PI3Kδ and moderate δ-isoenzyme selectivity over other class I PI3K isoforms and mTOR (with IC₅₀ values of 14.6, 34.0, 849.0 and 15.4 nM for PI3Kα, β, γ and mTOR, resp.). An in vitro MTT assay was conducted to assess the antiproliferative and cytotoxic effects of the prepared analogs. It was revealed that the compounds displayed significant inhibitory activities against the HCT116 human colon cancer cell line. Compound I [R = morpholino] showed 4.7-fold higher potency than the pos. control gedatolisib (0.3 vs. 1.4μM, IC₅₀ values). Phosphoblot studies demonstrated that I [R = morpholino, (2R)-2-carbamoylpyrrolidin-1-yl] could significantly suppress the PI3K/Akt/mTOR signaling pathway at 10μM. Moreover, analogs I [R = morpholino, (2S)-2-carbamoylpyrrolidin-1-yl, (2R)-2-carbamoylpyrrolidin-1-yl] displayed better stability in artificial gastric fluids than gedatolisib, while I [R = morpholino] was indicated not very stable in rat liver microsomes, and may occur phase I metabolic transformations.

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 C9H8BrNO4, Application In Synthesis of 39546-32-2.

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

Meng, Genyi published the artcileModular click chemistry libraries for functional screens using a diazotizing reagent, Safety of (1-Methylpiperidin-3-yl)methanamine, the publication is Nature (London, United Kingdom) (2019), 574(7776), 86-89, database is CAplus and MEDLINE.

Alkyl and aryl azides were prepared from the corresponding primary alkyl and aryl amines by reaction with fluorosulfonyl azide generated in situ from a fluorosulfonylimidazolium triflate and sodium azide, expanding access to azides and both to the 1,2,3-triazoles derived from them and to functional screens employing them. The method allowed the preparation of a library of >1000 azides from the corresponding amines; the azide library underwent copper-catalyzed azide-alkyne cycloaddition reactions to yield a library of >1000 1,2,3-triazoles.

Nature (London, United Kingdom) 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, Safety of (1-Methylpiperidin-3-yl)methanamine.

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

Lefebvre, Carole-Anne published the artcileSynthesis of novel substituted pyrimidine derivatives bearing a sulfamide group and their in vitro cancer growth inhibition activity, COA of Formula: C6H12N2O, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(2), 299-302, database is CAplus and MEDLINE.

The synthesis of two series of novel substituted pyrimidine derivatives bearing a sulfamide group have been described and their in vitro cancer growth inhibition activities have been evaluated against three human tumor cell lines (HT-29, M21, and MCF7). In general, growth inhibition activity has been enhanced by the introduction of a bulky substituent on the aromatic ring with the best compound having GI₅₀ < 6 μM for all the human tumor cell lines. The MCF7 selective compounds were evaluated on four addnl. human invasive breast ductal carcinoma cell lines (MDA-MB-231, MDA-MB-468, SKBR3, and T47D) and were selective against T47D cell line in all cases except one, suggesting a potential antiestrogen activity.

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, COA of Formula: C6H12N2O.

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

Mathison, Ian W. published the artcileNew compounds. N,N-dimethyl-[3-(1-alkylpiperidy)]carbamates, potential cholinesterase inhibitors, COA of Formula: C7H15NO, the publication is Journal of Pharmaceutical Sciences (1973), 62(1), 158-60, database is CAplus and MEDLINE.

Ten 1-alkylpiperidinyl carbamates [I, R = Me, Et, Me(CH2), n = 2-8] were prepared by condensation of 1-alkyl-3-hydroxypiperidines with Me2NCOCl or by treatment of the hydroxy compound with Cl2CO followed by Me2NH.

Journal of Pharmaceutical Sciences 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, COA of Formula: C7H15NO.

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

Steiner, Gerd published the artcileTricyclic epines. Novel (E)- and (Z)-11H-dibenz[b,e]azepines as potential central nervous system agents. Variation of the basic side chain, Name: (1-Methylpiperidin-3-yl)methanamine, the publication is Journal of Medicinal Chemistry (1986), 29(10), 1877-88, database is CAplus and MEDLINE.

Dibenzazepinylideneacetonitriles I (R = alkylamino, aminoalkoxy; R¹ = H, Me, Cl; R² = H, Cl) were prepared and their pharmacol. activities were determined The introduction of the cyanomethylene group into the 11-position of the 11H-dibenz[b,e]azepine framework was carried out by a Wittig-Horner reaction under mild conditions. The (E),(Z) isomers were separated by fractional crystallization, assignment being achieved by X-ray anal. I (R = 4-methyl-1-piperazinyl, R¹ = R² = H; R¹ = 3-Me 3-Cl, R² = H; R¹ = H, R² = 8-Cl) show neuroleptic activity 2-7 times that of clozapine. The screening included tests for sedative and anticholinergic activity in mice, apomorphine and tryptamine antagonism in rats, and muscle-relaxing activity in rabbits. The divergence in the activity profile in the case of the separated (E),(Z) isomers has been observed as an interesting new aspect: the (Z) isomers show a significantly higher sedative and muscle-relaxant activity, whereas the (E) isomers possess a higher anticholinergic efficacy and somewhat greater apomorphine antagonism. Broad changes in the basic side chain were made in order to investigate structure-activity relationships. The important geometrical parameters for the mols., obtained by X-ray anal., were compared with the corresponding features in dopamine agonists and antagonists.

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 C25H23NO4, Name: (1-Methylpiperidin-3-yl)methanamine.

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

Biel, John H. published the artcileAntispasmodics. I. Substituted acetic acid esters of 1-alkyl-3-hydroxypiperidine, Product Details of C7H15NO, the publication is Journal of the American Chemical Society (1952), 1485-8, database is CAplus.

A modification of the method of Paul and Tchelitcheff (C.A. 40, 3757.9) for the preparation of 1-alkyl-3-hydroxypiperidines from furfural (I) or tetrahydrofurfural (II) gave consistently high yields of the alcs. The substituted acetates of the alcs. were potent acetylcholine antagonists. 3-Hydroxypyridine diphenylacetate (III) showed no spasmolytic properties. Tetrahydrofurfuryl chloride (36.0 g.), 68.0 g. Et₂NH, 90.0 g. NaI, and 150 cc. absolute EtOH heated 3 days in a citrate bottle on the steam bath, the mixture filtered, the filtrate evaporated, the residue in water acidified with dilute HCl and extracted with Et₂O, the aqueous phase saturated with KOH, and extracted with Et₂O yielded 25.4 g. N,N-diethyltetrahydrofurfurylamine (IV), b. 64-5°. Reductive aminolysis of I over Raney Ni at 70-90° yielded 71% N-ethyltetrahydrofurfurylamine (V). V (87.0 g.) or 106 g. IV in 54 cc. AcOH at 100-5° treated with 110 g. HBr during 2 h., the mixture neutralized with concentrated KOH below 30°, 350 g. KOH in 300 cc. water added, the mixture distilled, the distillate saturated with KOH and extracted with Et₂O yielded 70 g. N-ethyl-3-hydroxypiperidine (VI), b₁₅ 92-4°; benzoate m. 199-200°. 3-Hydroxypyridine (VII).HCl (39.1 g.) in 250 cc. absolute EtOH hydrogenated at 60 lb. H over 2.2 g. PtO₂ gave 9.0 g. 3-hydroxypiperidine (VIII), m. 61-3°; piperidine-HCl, m. 249-50°. VIII (3.8 g.), 2.3 g. KOH, and 5.9 g. EtI in absolute EtOH refluxed 18 h., cooled, filtered, the filtrate acidified with concentrated HCl, concentrated to dryness in vacuo, the residue dissolved in water and extracted with Et₂O and the aqueous phase saturated with KOH and extracted with Et₂O yielded 4.0 g. VI b₁₅ 93-5°. N-Methyl-3-hydroxypiperidine (IX) prepared in 70% yield from N-methyltetrahydrofurfurylamine b₁₅ 80-2°. VIII (9.0 g.), 13.1 g. 88% HCO₂H, and 8.9 g. 37% HCHO refluxed 24 h. yielded 7.0 g. IX, b₁₅ 81°. PhCH₂CN (117 g.) added during 10 min. to 44.0 g. NaNH₂ in 150 cc. C₆H₆, the mixture refluxed 3 h., 163.0 g. bromocyclohexane in 150 cc. C₆H₆ added at a rate that maintained reflux, the mixture refluxed 8 h., cooled, 250 cc. water added, and the C₆H₆ layer distilled yielded 150 g. α-cyclohexylbenzylnitrile (X), b_0.2 mm. 128-30°, m. 56-8°. Hydrolysis of X yielded 92% phenylcyclohexylacetic acid (XI), m. 153-4°. Ph₂C(OH)CO₂H (22.8 g.) in 150 cc. AcOH at 100° hydrogenated at 60 lb. over PtO₂ yielded 12.7 g. phenylcyclohexylglycolic acid (XII), m. 161-3°. The method of Hoffmann and Schellenberg (C.A. 41, 3074g) yielded 28% phenylcyclopentylglycolic acid (XIII), m. 147-8°. VII (9.5 g.), 23.6 g. Ph₂CHCOCl (XIV), and 50 cc. pyridine refluxed 8 h., the mixture chilled, poured into 600 cc. ice water, the aqueous mixture extracted with Et₂O, the Et₂O evaporated, and the ester distilled in vacuo yielded 26.0 g. III, b_0.5 188-90°; HCl salt (XV), m. 151-2°. XV (26.0 g.) hydrogenated at 60 lb. over 0.5 g. PtO₂, the mixture filtered, the filtrate concentrated in vacuo, the residue in 300 cc. Et₂O refluxed 1 h., filtered, the solid dissolved in water, the solution saturated with KOH, extracted with Et₂O (yielding 3 g. piperidine), the Et₂O filtrate concentrated to dryness, the residue (15 g.) in 200 cc. petr. ether refluxed 1 h., filtered hot [yielding 6.6 g. Ph₂CHCO₂H (XVI), m. 146-8°], and the filtrate cooled yielded 6.0 g. Ph₂CHCO₂Et (XVII), m. 60-60.5°. XVI with LiAlH₄ yielded 77% Ph₂CHCH₂OH, m. 58-9°. XIV and excess NaOEt in absolute EtOH heated a few min. and poured into ice water yielded 80% XVII, m. 59-60°. III (5.0 g.) and 15.0 g. MeI in Et₂O let stand 2 wk in the dark yielded 2.1 g. methiodide, m. 126-8°. N-Alkyl-3-piperidyl esters. Procedure A: XIV (46.0 g.), 25.8 g. VI, and 100 cc. pyridine refluxed 4 h., poured into 800 cc. ice water, the aqueous phase extracted with Et₂O and the extracts evaporated yielded 52.0 g. N-ethyl-3-piperidyl diphenylacetate-HCl. Procedure B: Ph₂C(OH)CO₂H (47.0 g.), 30.5 g. N-ethyl-3-chloropiperidine, and 130 cc. iso-PrOH refluxed 72 h., the solvent removed in vacuo, the residue poured into 200 cc. ice water, acidified with concentrated HCl, extracted with Et₂O, the aqueous layer made alk. with 12 g. NaOH and extracted with Et₂O yielded 49.0 g. N-ethyl-3-piperidyl benzilate-HCl (XVIII), m. 189-90°. Procedure C: The Et ester of XII (21.0 g.), 17.0 g. IX, 0.3 g. Na, and 100 cc. xylene heated at 165° in an oil bath (water and xylene slowly distilled) during 16 h., water, IX, and xylene removed in vacuo, the residue in water acidified with HCl, the aqueous layer extracted with Et₂O, made alk. with KOH, and extracted with Et₂O yielded 3.6 g. N-methyl-3-piperidyl 1-phenylcyclohexylcarboxylate HCl salt, m. 215-16°. XVIII (3.76 g.), and 16.0 g. KOH in alc. refluxed 24 h. yielded 1.2 g. VI, b₁₂ 86-8°; benzoate-HCl, m. 198-9°. Other RCO₂R’ (R’ = 1-ethyl-3-piperidyl) prepared are (R, b.p./mm., salt, and its m.p. given): Ph₂CH, 191-2°/0.18, HCl, 195-6° (MeBr salt, m. 168-9°); Ph(C₆H₁₁)CH, 172-4°/0.55, HCl, 214-16° (MeBr salt, m. 126-7°); Ph₂COH, 207-8°/0.50, HCl, 187-8° (MeBr salt, m. 179-80°); Ph(C₆H₁₁)COH, 166-7°/0.5, HCl, 215-17°; 9-fluorene, -, HCl 226-7°;9-xanthene, -, HCl, 226-7°. Ph₂CHCO₂R (R = 1-methyl-3-piperidyl) b_0.16 173-5° (HCl salt, m. 193-4°).

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 C7H15NO, Product Details of C7H15NO.

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

Rzasa, Robert M. published the artcileSynthesis and preliminary biological evaluation of potent and selective 2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors with improved solubility, Safety of Piperidine-4-carboxamide, the publication is Bioorganic & Medicinal Chemistry (2014), 22(23), 6570-6585, database is CAplus and MEDLINE.

We report the discovery of a novel series of 2-(3-alkoxy-1-azetidinyl) quinolines as potent and selective PDE10A inhibitors. Structure-activity studies improved the solubility (pH 7.4) and maintained high PDE10A activity compared to initial lead compound 3, with select compounds demonstrating good oral bioavailability. X-ray crystallog. studies revealed two distinct binding modes to the catalytic site of the PDE10A enzyme. An ex vivo receptor occupancy assay in rats demonstrated that this series of compounds covered the target within the striatum.

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, Safety of Piperidine-4-carboxamide.

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