Month: December 2022

Yousif, M. N. M. published the artcileSynthesis and Biological Activity of Triacetonamine, Name: 2,2,6,6-Tetramethylpiperidin-4-one, the publication is Russian Journal of General Chemistry (2020), 90(3), 460-469, database is CAplus.

A review. Various methods of synthesis of 2,2,6,6-tetramethylpiperidin-4-one (triacetonamine) derivatives start generally with acetone, phorone, piperidine N-oxides, piperidine alcs., and 4-dimethylamine piperidine derivatives Phys. properties of triacetonamine including d., b.p., flash point, and m.p. were determined Reactions of triacetonamine derivatives with various organic reagents were also summarized. Triacetonamine derivatives react via three functional groups including carbonyl, methylenes adjacent to the carbonyl group, and NH. Some other miscellaneous reactions and conformation of triacetonamine were described. Theor. models for the conformations of triacetonamine were developed by quantum and mol. mechanics methods. Triacetonamine demonstrated different types of biol. activities, such as antialzheimer, antifungal, antimicrobial, anti-HIV, anticancer, antioxidant, P38 kinase inhibitor, DNA labeling, antispasmodic, and psychotropic, and high ganglionic blocking.

Russian Journal of General Chemistry 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 C9H9BrO2, Name: 2,2,6,6-Tetramethylpiperidin-4-one.

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

Owens, Timothy D. published the artcilePhase 1 clinical trial evaluating safety, exposure and pharmacodynamics of BTK inhibitor tolebrutinib (PRN2246, SAR442168), Application of (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, the publication is Clinical and Translational Science (2022), 15(2), 442-450, database is CAplus and MEDLINE.

Bruton′s tyrosine kinase (BTK), expressed in B cells and cells of innate immunity, including microglia, is an essential signaling element downstream of the B-cell receptor and Fc-receptors. Tolebrutinib (PRN2246, SAR442168) is a potent BTK inhibitor that covalently binds the kinase, resulting in durable inhibition with the potential to target inflammation in the periphery and central nervous system (CNS). Tolebrutinib crosses the blood-brain barrier and potently inhibits BTK in microglial cells isolated from the CNS. A first-in-human randomized, double-blind, placebo-controlled study of tolebrutinib was conducted. The trial design consisted of five single ascending dose arms with oral administration of a single dose of 5, 15, 30, 60, and 120 mg (n = 6 per arm, n = 2 placebo), five multiple ascending dose arms with oral administration of 7.5, 15, 30, 60, and 90 mg (n = 8 per arm, n = 2 placebo) over 10 days, and one arm (n = 4) in which cerebral spinal fluid (CSF) exposure was measured 2 h after a single 120 mg dose. Tolebrutinib was well-tolerated in the study and all treatment-related treatment emergent adverse events were mild. Tolebrutinib was rapidly absorbed following oral administration with a rapid half-life of ∼ 2 h. Peripheral BTK occupancy was assessed at various timepoints by an ELISA-based readout using an irreversible probe. Assessments demonstrated extensive and prolonged peripheral BTK occupancy at steady-state with once daily doses as low as 7.5 mg. Further, CSF exposure was demonstrated 2 h after administration at 120 mg.

Clinical and Translational Science published new progress about 1971920-73-6. 1971920-73-6 belongs to piperidines, auxiliary class Other Aliphatic Heterocyclic,Piperidine,Alkenyl,Amine,Benzene,Ether,Inhibitor,Inhibitor, name is (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, and the molecular formula is C26H25N5O3, Application of (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one.

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

Crich, David published the artcile1-Benzenesulfinyl Piperidine/Trifluoromethanesulfonic Anhydride: A Potent Combination of Shelf-Stable Reagents for the Low-Temperature Conversion of Thioglycosides to Glycosyl Triflates and for the Formation of Diverse Glycosidic Linkages, HPLC of Formula: 4972-31-0, the publication is Journal of the American Chemical Society (2001), 123(37), 9015-9020, database is CAplus and MEDLINE.

The combination of 1-benzenesulfinyl piperidine (BSP) and trifluoromethanesulfonic anhydride (Tf₂O) forms a new, powerful, metal-free thiophile that can readily activate both armed and disarmed thio glycosides, via glycosyl triflates, in a matter of minutes at -60 °C in dichloromethane, in the presence of 2,4,6-tri-tert-butylpyrimidine (TTBP). The glycosyl triflates are rapidly and cleanly converted to glycosides, upon treatment with alcs., in good yield and selectivity.

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, HPLC of Formula: 4972-31-0.

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

Buehler, C. A. published the artcilePhysiologically active compounds. II. Hydrochlorides of aminoesters of substituted benzilic and glycolic acids, Synthetic Route of 13444-24-1, the publication is Journal of Organic Chemistry (1958), 1432-7, database is CAplus.

cf. C.A. 51, 17843h. Aminoester hydrochlorides of 39 substituted benzilic and glycolic acids were synthesized; 2 of them appear to be more active in exptl. animals than atropine in preventing mortality from an anticholinesterase compound, and 4 of them exhibit the highest anticholinergic activity. One compound previously reported offers some advantage over these as an anticholinergic. β-Aminoethyl chlorides were prepared by the procedures given in the previous paper. Tetrahydrofurfuryl alc. with SOCl₂ gave 73% tetrahydrofurfuryl chloride (I). I, NHEt₃, and NaI gave 53% N,N-diethyltetrahydrofurfurylamine (II). II was converted by HBr to 80% N-ethyl-3-hydroxypiperidine (III). III with SOCl₂ gave N-ethyl-3-chloropiperidine-HCl which with aqueous NaOH gave the free N-ethyl-3-chloropiperidine. The following RR’C(OH)CO₂(CH₂)_xR”.HCl were prepared by refluxing the proper benzilic acid with the aminoethyl chloride in dry iso-PrOH (R, R’, R”, Χ, % yield, and m.p. given): 2-MeC₆H₄, 2-MeC₆H₄, N-ethyl-3-piperidyl (IV), 0, 69, 186-7°; 3-MeC₆H₄, 3-MeC₆H₄, N-ethyl-3-piperidyl, 0, 81, 150-1°; 4-iso-PrC₆H₄, 4-iso-PrC₆H₄, Et₄N, 2, 64, 181-2°; 2-MeOC₆H₄, 2-MeOC₆H₄, Et₂N, 2, 65, 171-2°; 4-MeOC₆H₄, 4-MeOC₆H₄, Et₂N, 2, 77, 167-8.5°; 4-MeOC₆H₄, 4-MeOC₆H₄, pyrrolidino, 2, 92, 181-2°; 4-MeOC₆H₄, 4-MeOC₆H₄, pyrrolidino (MeBr derivative), 2, 53, 147-8°; 2,3-(MeO)₂C₆H₃, 2,3-(MeO)₂C₆H₃, Et₂N (V), 2, 83, 184-5°; 3,4-(MeO)₂C₆H₃, 3,4-(MeO)₂C₆H₃, Et₂N, 2, 79, 167.5-8.5°; 3,4-methylenedioxyphenyl, Ph, Et₂N (VI), 2, 73, 164-5.5°; 3-PhC₆H₄, Ph, Et₂N, 2, 73, 136-7°; 3-PhC₆H₄, Ph, Et₂N (VII), 2, 60, 178-9°; 4-PhC₆H₄, Ph, piperidyl, 2, 70, 189-90°; 4-PhC₆H₄, Ph, N-ethyl-3-piperidyl (VIII), 0, 65, 149-50°; 3-PhC₆H₄, 3-PhC₆H₄, Et₂N (IX), 2, 59, 158-9°; 3-PhC₆H₄, 3-PhC₆H₄, piperidino, 2, 68, 197-8°; 4-PhC₆H₄, 4-PhC₆H₄, Et₂N, 2, 72, 183-5°; 4-PhC₆H₄, 4-PhC₆H₄, piperidino (X), 2, 47, 192-3°; 4-PhC₆H₄, 4-PhC₆H₄, N-ethyl-3-piperidyl (XI), 0, 74, 190-1°. 2-Phenylbenzilic acid could be prepared neither by an analogous procedure from 2-bromobiphenyl through the action of 2-biphenylmagnesium iodide on isonitrosoacetophenone nor through a mixed benzoin condensation of BzH and 2-PhC₆H₄CHO (XIa). The Grignard reagent of 3-bromobiphenyl (XII) reacted with N-methylformanilide to form 3-phenylbenzaldehyde (XIII) which was subjected to the benzoin condensation to give 3,3′-diphenylbenzoin (XIV). XIV was oxidized with CuSO₄ in C₅H₅N to the corresponding benzil (XV) which on rearrangement with KOH gave 3,3′-diphenylbenzilic acid (XVI). 2,2′-Diphenylbenzilic acid could not be produced because of the failure of XIa to undergo the benzoin condensation. XII and Et phenylglyoxylate (XVII) were prepared by known methods. XII (23.4 g.) in 300 ml. Et₂O added dropwise to 2.51 g. Mg and Et₂O under N, the solution refluxed 2 hrs., the Grignard solution added dropwise to 17.8 g. XVII in 200 ml. Et₂O, the solution refluxed 2 hrs., 250 ml. dilute HCl added, the Et₂O layer separated, the H₂O portion extracted with more Et₂O, the extracts combined, and distilled gave 18 g. Et 3-phenylbenzilate (XVIII), b₁ 213-18°. XVIII (18 g.) in 30 ml. alc. refluxed 3 hrs. with 20 g. KOH in 100 ml. H₂O, diluted with H₂O, acidified, and the precipitate collected gave 11 g. 3-phenylbenzilic acid, m. 127-8° (C₆H₆). XII (23.4 g.) in 250 ml. Et₂O treated with 2.51 g. Mg, then 13.5 g. N-methylformanilide added during 2 hrs., stirred 1 hr., decomposed, and separated gave 14 g. XIII, b₂ 138-44°; 2,4-dinitrophenylhydrazone, m. 234-5°. XIII (8 g.), 3 g. KCN, 40 ml. H₂O, and 80 ml. alc. refluxed. 10 hrs., cooled, diluted with H₂O, extracted with Et₂O, dried, and distilled gave 6 g. orange oil. This oil, 14 g. CuSO₄, 100 ml. C₅H₅N, and 30 ml. H₂O refluxed 6 hrs., the mixture poured onto ice and H₂O, the liquid decanted, and the solid dissolved in alc. gave 2.7 g. XV, m. 119-20° (MeOH); quinoxaline, m. 156°. XV (8 g.) in 300 ml. Et₂O left 24 hrs. with frequent shaking with 4 g. Na in 50 ml. 95% alc. and 25 ml. absolute alc., the solution extracted with H₂O, the aqueous solution extracted with Et₂O, heated to 90°, and acidified gave 3 g. crude XVI, m. 155-7° (C₆H₆). RR’C(OH)CO₂CH₂CH₂NEt₂.HCl (XIX) were prepared by dissolving 0.01 mole corresponding benzilate in AcOH, hydrogenating at 3 atm. over 0.1 g. Pt catalyst until reduction was complete, removing the catalyst and AcOH, and crystallizing the solid to give pure XIX. The following XIX were thus prepared (R, R’, % yield, and m.p. given): C₆H₁₁, C₆H₁₁, 72, 258-9°; C₆H₁₁, C₆H₁₁, 35, 212-13°; 2-MeC₆H₁₀, C₆H₁₁, 76, 165-6.5°; 3-MeC₆H₁₀, C₆H₁₁, 86, 181-2°; 4-MeC₆H₁₀, C₆H₁₁ (XX), 87, 190.5-2.0°; 2-MeC₆H₁₀, 2-MeC₆H₁₀, 80, 163.5-4.5°; 2,3-Me₂C₆H₉, C₆H₁₁, 79, 174-5°; 2,4-Me₂C₆H₉, C₆H₁₁, 79, 155-6°; 2,6-Me₂C₆H₉, C₆H₁₁, 81, 181-2°; 3,4-Me₂C₆H₉, C₆H₁₁, 80, 177.5-8.5°; 3,5-Me₂C₆H₉, C₆H₁₁, 73, 171.5-3.0°; 3-MeC₆H₁₀, 3-MeC₆H₁₀, 84, 178.5-9.5°; 4-MeC₆H₁₀, 4-MeC₆H₁₀, 82, 187-8°; 2,3,5-Me₃C₆H₈, C₆H₁₁, 76, 193-4°; 3,4,5-Me₃C₆H₈, C₆H₁₁ (XXI), 90, 216.5-18.0°; 3,5-Me₂C₆H₉, 3,5-Me₂C₆H₉, 84, 183-4°; 4-iso-PrC₆H₁₀, 4-iso-PrC₆H₁₀, 84, 185-7°; 3-C₆H₁₁C₆H₁₀, C₆H₁₁, 43, 133-4°; 4-C₆H₁₁C₆H₁₀, C₆H₁₁, 74, 174.5-5.5°; 2,3,6-Me₃C₆H₈, C₆H₁₁, 76, 199-200°. The above method was used to prepare all of the above XIX except with the di-C₆H₁₁ member in which the unreduced ester was prepared by the method of Hill and Holmes (U.S. 2,294,770) wherein the Me ester was refluxed with the appropriate amino alc. These compounds were tested for anticholinesterase activity, blood pressure, gut, respiration, and eye effects. VII and VIII appeared to be more active than atropine in preventing mortality from an anticholesterase compound The most active anticholinergic compounds are VI, XX, and XXI. VI and XXI are surpassed in activity by a previously prepared compound; this compound has much more marked effects on blood pressure and respiration than any of the 4 new compounds Compounds effective in dilating the pupil of the eye without significant irritant action are IV, V, VI, VIII, X, and XI. 3-PhC₆H₄CPh(OH)CO₂(CH₂)₂NEt₂.HCl and IX, which resemble V and VI in being diethylaminoethanol derivatives, are as active as the latter 2 compounds in dilating the pupil, but are definitely irritating.

Journal of Organic 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, Synthetic Route of 13444-24-1.

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

Meerovich, Igor published the artcileDirect solid-phase peptide synthesis on chitosan microparticles for targeting tumor cells, Quality Control of 35661-58-6, the publication is Journal of Drug Delivery Science and Technology (2019), 101288, database is CAplus.

An EGFR-targeting peptide with Ala-Glu-Tyr-Leu-Arg sequence was assembled directly onto the surface of spray-dried chitosan microparticles using solid-phase peptide synthesis with Fmoc chem. Both targeted and scrambled peptides were cleaved from chitosan with enzymic digestion, isolated using reversed-phase HPLC, then identified with LC/MS/MS and amino acid anal. Particles with conjugated peptides and fluorescent-labeled were characterized for binding with A549 (cancer) and WI-26 VA4 (normal) lung cells using flow cytometry and confocal microscopy. The purity of peptide synthesis was in the range of 74-77%. The cell binding studies revealed that particles modified with the peptide bind to lung cancer cells 8.3 times higher than the normal lung cells. The binding potential of surface-modified targeted particles to the tumor cells was compared with scrambled and unmodified ones and was found to be significantly different. The binding was 7.3-7.5-fold higher than the scrambled and unmodified particles, resp. Modification of chitosan particles with direct assembly of Ala-Glu-Tyr-Leu-Arg peptide on their surface enhanced their targeting potential to lung cancer cells and could be used as a potential carrier for delivery and therapy. This approach can further be utilized for assembly of other short peptide ligands on micro- or nanoparticulate systems for tumor targeting.

Journal of Drug Delivery Science and Technology 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, Quality Control of 35661-58-6.

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

Rink, Hans published the artcileConversion of N^G-urethane protected arginine to ornithine in peptide solid-phase synthesis, Product Details of C19H21N, the publication is Tetrahedron Letters (1984), 25(6), 621-4, database is CAplus.

During solid-phase peptide synthesis, guanidino protection by adamantyloxycarbonyl (Adoc) or Me₃CO₂C (Boc) groups does not effectively prevent guanidino acylation and subsequent partial conversion of arginine residues to ornithine residues when strongly basic conditions are used to remove α-amino protecting groups. Thus, Z-Phe-Ser(CMe₃)-Leu-Ser(CMe₃)-Lys(Boc)-Ile-Phe-Gln-Glu(OCMe₃)-Arg(Adoc)₂-Leu-Arg(Adoc)₂-Arg(Adoc)₂-Lys(Boc)-Glu(OCMe₃)-OCH₂-resin (I, Z = PhCH₂O₂C, CH₂-resin = acid-labile p-benzyloxybenzyl alc. resin) was prepared by the solid-phase method using 9-fluorenyloxycarbonyl (Fmoc) amino acids and then I was cleaved and deblocked to give Z-Phe-Ser-Leu-Ser-Lys-Ile-Phe-Gln-Glu-X-Leu-Orn-Arg-Lys-Glu-OH (X = Orn, Arg). The above arginine to ornithine conversion was confirmed by the following model reactions. Boc-Arg(Adoc)₂-OMe was treated with (Fmoc-Phe)₂O to give arginine II, which was Fmoc-deblocked by piperidine/DMF to give Boc-Orn(Adoc)-OMe, fluorene III, and imidazolinone IV.

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, Product Details of C19H21N.

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

Vystorop, I. V. published the artcileRegioselective Synthesis, Structure, and Chemosensitizing Antitumor Activity of Cyclic Hydroxamic Acid Based on DL-Valine, Product Details of C9H17NO, the publication is Russian Journal of Bioorganic Chemistry (2021), 47(3), 757-764, database is CAplus.

The reaction of DL-valine hydroxamic acid with triacetonamine proceeds as the N,N’-regioselective condensation to form (±)-1-hydroxy-3-isopropyl-7,7,9,9-tetramethyl-1,4,8-triazaspiro[4,5]decan-2-one. A study of the antimetastatic and antitumor activities of the resulting hydroxamic acid in vivo by the combined therapy with a cytostatic of the alkylation type on a model of exptl. transplanted mouse melanoma B16 showed that the compound is capable of increasing the sensitivity of the tumor to the known antitumor drug cyclophosphamide applied at a subtherapeutic dose. The chemosensitizing activity of hydroxamic acid combined with cyclophosphamide led to an almost twofold increase in the antitumor effect of the cytostatic and a marked decrease in the number of metastases, which showed up as an increase in the metastasis inhibition index (MII) to 74%.

Russian Journal of Bioorganic Chemistry 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 C10H15ClO3S, Product Details of C9H17NO.

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

Luo, Zonghua published the artcileSynthesis and Evaluation of Multi-Target-Directed Ligands against Alzheimer’s Disease Based on the Fusion of Donepezil and Ebselen, COA of Formula: C6H12N2O, the publication is Journal of Medicinal Chemistry (2013), 56(22), 9089-9099, database is CAplus and MEDLINE.

Benzylpiperidinylalkyl benzoisoselenazolones I [R = H, MeO; R¹ = H, Cl, F, MeO; X = (CH₂)_n; n = 1-4] were prepared as donepezil-ebselen hybrids for potential use as anti-Alzheimer’s disease agents. I (R = R¹ = MeO; n = 2) was one of the most potent acetylcholinesterase inhibitors of the compounds tested (IC₅₀ values of 0.042 μM for Electrophorus electricus acetylcholinesterase and 0.097 μM for human acetylcholinesterase) and was found to be a strong butyrylcholinesterase inhibitor with an IC₅₀ value of 1.586 μM, to possess rapid H₂O₂ and peroxynitrite scavenging activity and glutathione peroxidase-like activity (ν₀ = 123.5 μM min^-1), and to be a substrate of mammalian thioredoxin reductase. I (R = R¹ = MeO; n = 2) showed no acute toxicity at doses of up to 2000 mg/kg; by comparing its permeation in an artificial blood-brain barrier permeation assay, I (R = R¹ = MeO; n = 2) was expected to be able to penetrate the central nervous system.

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, COA of Formula: C6H12N2O.

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

Mamros, Audrey N. published the artcileOxidation of primary and secondary alcohols by 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate in aqueous media, Product Details of C11H21BF4N2O2, the publication is ARKIVOC (Gainesville, FL, United States) (2011), 23-33, database is CAplus.

The water-soluble oxidant 4-(acetylamino)-2,2,6,6-tetramethyl-1-oxopiperidinium tetrafluoroborate oxidized primary and secondary aliphatic, primary allylic, and primary and secondary benzylic alcs. to the corresponding aldehydes and ketones in aqueous media in good to excellent yields.

ARKIVOC (Gainesville, FL, 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, Product Details of C11H21BF4N2O2.

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

Crich, David published the artcileInfluence of the O3 Protecting Group on Stereoselectivity in the Preparation of C-Mannopyranosides with 4,6-O-Benzylidene Protected Donors, Synthetic Route of 4972-31-0, the publication is Journal of Organic Chemistry (2010), 75(24), 8383-8391, database is CAplus and MEDLINE.

α-C-Glucopyranosides and mannopyranosides are obtained in 65-85% yields from 4,6-O-benzylidene-protected glucosyl and mannosyl thioglycosides bearing ester functionality at the 3-O-position by a coupling reaction with C-nucleophiles on activation with di-Ph sulfoxide, 2,4,6-tri-tert-butylpyrimidine, and trifluoromethanesulfonic anhydride.

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, Synthetic Route of 4972-31-0.

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