Category: piperidines

Luxenburger, Andreas published the artcileDiscovery of AL-GDa62 as a Potential Synthetic Lethal Lead for the Treatment of Gastric Cancer, Related Products of piperidines, the publication is Journal of Medicinal Chemistry (2021), 64(24), 18114-18142, database is CAplus and MEDLINE.

Diffuse gastric cancer and lobular breast cancer are aggressive malignancies that are frequently associated with inactivating mutations in the tumor suppressor gene CDH1. Synthetic lethal (SL) vulnerabilities arising from CDH1 dysfunction represent attractive targets for drug development. Recently, SLEC-11 (1) emerged as a SL lead in E-cadherin-deficient cells. Here, we describe our efforts to optimize 1. Overall, 63 analogs were synthesized and tested for their SL activity toward isogenic mammary epithelial CDH1-deficient cells (MCF10A-CDH1^-/-). Among the 26 compounds with greater cytotoxicity, AL-GDa62 (3)(I) was four-times more potent and more selective than 1 with an EC₅₀ ratio of 1.6. Furthermore, 3 preferentially induced apoptosis in CDH1^-/- cells, and Cdh1^-/- mammary and gastric organoids were significantly more sensitive to 3 at low micromolar concentrations Thermal proteome profiling of treated MCF10A-CDH1^-/- cell protein lysates revealed that 3 specifically inhibits TCOF1, ARPC5, and UBC9. In vitro, 3 inhibited SUMOylation at low micromolar concentrations

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 C7H16N2, Related Products of piperidines.

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

Marchand-Brynaert, Jacqueline published the artcileDesign and synthesis of functionalized oxaziridines as topological analogs of penicillins, SDS of cas: 35661-58-6, the publication is Israel Journal of Chemistry (1989), 29(2-3), 247-55, database is CAplus.

Oxaziridines were examined as potential alkylating inhibitors of bacterial serine D,D-peptidases. Structures were designed to mimic known β-lactam antibiotics taking into account stereoelectronic requirements for a nucleophilic attack on a 3-membered ring. Novel oxaziridines, e.g., I (R = CO₂CMe₃, fluorenylmethyloxycarbonyl, COCH₂Ph, COCH₂OPh; R¹ = Me, allyl, SiPh₂CMe₃), with functionalized side chains were prepared They showed poor antibacterial activity in vitro, perhaps, as a result of their low chem. stability.

Israel Journal of Chemistry 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, SDS of cas: 35661-58-6.

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

Marchand-Brynaert, Jacqueline published the artcileDesign and Synthesis of Functionalized Oxaziridines as Topological Analogs of Penicillins, Product Details of C19H21N, the publication is Israel Journal of Chemistry (2013), 29(2-3), 247-255, database is CAplus.

Oxaziridines were examined as potential alkylating inhibitors of bacterial serine D,D-peptidases. Structures were designed to mimic known β-lactam antibiotics taking into account stereoelectronic requirements for a nucleophilic attack on a three-membered ring. Novel oxaziridines equipped with functionalized side chains were prepared They showed poor antibacterial activities in vitro, perhaps as a result of their low chem. stability.

Israel Journal of Chemistry 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

Heald, Robert published the artcileNoncovalent Mutant Selective Epidermal Growth Factor Receptor Inhibitors: A Lead Optimization Case Study, Category: piperidines, the publication is Journal of Medicinal Chemistry (2015), 58(22), 8877-8895, database is CAplus and MEDLINE.

Because of their increased activity against activating mutants, first-generation epidermal growth factor receptor (EGFR) kinase inhibitors have had remarkable success in treating non-small-cell lung cancer (NSCLC) patients, but acquired resistance, through a secondary mutation of the gatekeeper residue, means that clin. responses only last for 8-14 mo. Addressing this unmet medical need requires agents that can target both of the most common double mutants: T790M/L858R (TMLR) and T790M/del(746-750) (TMdel). Herein we describe how a noncovalent double mutant selective lead compound was optimized using a strategy focused on the structure-guided increase in potency without added lipophilicity or reduction of three-dimensional character. Following successive rounds of design and synthesis it was discovered that cis-fluoro substitution on 4-hydroxy- and 4-methoxypiperidinyl groups provided synergistic, substantial, and specific potency gain through direct interaction with the enzyme and/or effects on the proximal ligand oxygen atom. Further development of the fluorohydroxypiperidine series resulted in the identification of a pair of diastereomers that showed 50-fold enzyme and cell based selectivity for T790M mutants over wild-type EGFR (wtEGFR) in vitro and pathway knock-down in an in vivo xenograft model.

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, Category: piperidines.

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

Ball, Matthew published the artcileDevelopment of a Manufacturing Route to Avibactam, a β-Lactamase Inhibitor, Quality Control of 1416134-49-0, the publication is Organic Process Research & Development (2016), 20(10), 1799-1805, database is CAplus.

Process development work to provide an efficient, robust, and cost-effective manufacturing route to avibactam, a β-lactamase inhibitor is presented herewith. Aspects of this optimization work include the counterintuitive introduction of a protecting group to effect a difficult urea formation and the use of controlled feed hydrogenation conditions to facilitate an elegant one pot debenzylation and sulfation reaction. Overall, the com. process delivers avibactam in much improved yield with significant reduction in the environmental footprint.

Organic Process Research & Development published new progress about 1416134-49-0. 1416134-49-0 belongs to piperidines, auxiliary class Piperidine,Chiral,Amine,Benzene,Amide, name is (2S,5R)-5-((Benzyloxy)amino)piperidine-2-carboxamide, and the molecular formula is C13H19N3O2, Quality Control of 1416134-49-0.

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

Owens, Timothy D. published the artcileDiscovery of Reversible Covalent Bruton′s Tyrosine Kinase Inhibitors PRN473 and PRN1008 (Rilzabrutinib), Quality Control of 1971920-73-6, the publication is Journal of Medicinal Chemistry (2022), 65(7), 5300-5316, database is CAplus and MEDLINE.

Bruton′s tyrosine kinase (BTK), a Tec family tyrosine kinase, is critical in immune pathways as an essential intracellular signaling element, participating in both adaptive and immune responses. Currently approved BTK inhibitors are irreversible covalent inhibitors and limited to oncol. indications. Herein, we describe the design of covalent reversible BTK inhibitors and the discoveries of PRN473 (11) and rilzabrutinib (PRN1008, 12). These compounds have exhibited potent and durable inhibition of BTK, in vivo efficacy in rodent arthritis models, and clin. efficacy in canine pemphigus foliaceus. Compound 11 has completed phase 1 trials as a topical agent, and 12 is in phase 3 trials for pemphigus vulgaris and immune thrombocytopenia.

Journal of Medicinal Chemistry 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, Quality Control of 1971920-73-6.

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

Boy, Songuel published the artcileSynthesis, Spectroscopic Analysis, and in Vitro/in Silico Biological Studies of Novel Piperidine Derivatives Heterocyclic Schiff-Mannich Base Compounds, HPLC of Formula: 39546-32-2, the publication is Chemistry & Biodiversity (2021), 18(12), e2100433, database is CAplus and MEDLINE.

In the present study, 3-substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (S1-8) were synthesized by treating 4-hydroxybenzaldehyde (B) with eight different 3-substitued-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones (T1-8) in acetic acid medium, sep. The synthesized Schiff bases (S) were reacted with formaldehyde and secondary amine such as 4-piperidinecarboxyamide to afford novel heterocyclic bases. 3-Substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (T) were treated with 4-piperidinecarboxyamide in the presence of formaldehyde to synthesize eight new 1-(4-piperidinecarboxyamide-1-yl-methyl)-3-substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (M1-8). The structure characterization of compounds was carried out using 1H-NMR, IR, HR-MS, and 13C-NMR spectroscopic methods. The inhibitory properties of the newly synthesized compounds were calculated against the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione S-transferase (GST) enzymes. Ki values were calculated in the range of 20.06±3.11-36.86±6.17 μM for GST, 17.87±2.91-30.53±4.25 μM for AChE, 9.08±0.69-20.02±2.88 μM for BChE, resp., Besides, IC50 values were also calculated Best binding scores of -inhibitors against used enzymes were calculated as -12.095 kcal/mol, -12.775 kcal/mol, and -9.336 kcal/mol, resp. While 5-oxo-triazole piperidine-4-carboxamide moieties have a critical role in the inhibition of AChE and GST enzymes, hydroxy benzyl moiety is important for BChE enzyme inhibition.

Chemistry & Biodiversity 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, HPLC of Formula: 39546-32-2.

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

Ekholm, Filip S. published the artcileStudies Related to Norway Spruce Galactoglucomannans: Chemical Synthesis, Conformation Analysis, NMR Spectroscopic Characterization, and Molecular Recognition of Model Compounds, Product Details of C11H15NOS, the publication is Chemistry – A European Journal (2012), 18(45), 14392-14405, database is CAplus and MEDLINE.

Galactoglucomannan (GGM) is a polysaccharide mainly consisting of mannose, glucose, and galactose. GGM is the most abundant hemicellulose in the Norway spruce (Picea abies), but is also found in the cell wall of flax seeds, tobacco plants, and kiwi fruit. Although several applications for GGM polysaccharides have been developed in pulp and paper manufacturing and the food and medical industries, attempts to synthesize and study distinct fragments of this polysaccharide have not been reported previously. Herein, the synthesis of one of the core trisaccharide units of GGM together with a less-abundant tetrasaccharide fragment is described. In addition, detailed NMR spectroscopic characterization of the model compounds, comparison of the spectral data with natural GGM, investigation of the acetyl-group migration phenomena that takes place in the polysaccharide by using small model compounds, and a binding study between the tetrasaccharide model fragment and a galactose-binding protein (the toxin viscumin) are reported.

Chemistry – A European Journal 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, Product Details of C11H15NOS.

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

Reich, Daniel S. published the artcileSafety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial, Recommanded Product: (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, the publication is Lancet Neurology (2021), 20(9), 729-738, database is CAplus and MEDLINE.

Tolebrutinib is an oral, CNS-penetrant, irreversible inhibitor of Bruton’s tyrosine kinase, an enzyme expressed in B lymphocytes and myeloid cells including microglia, which are major drivers of inflammation in multiple sclerosis. We aimed to determine the dose-response relationship between tolebrutinib and the reduction in new active brain MRI lesions in patients with relapsing multiple sclerosis. We did a 16-wk, phase 2b, randomised, double-blind, placebo-controlled, crossover, dose-finding trial at 40 centers (academic sites, specialty clinics, and general neurol. centers) in ten countries in Europe and North America. Eligible participants were adults aged 18-55 years with diagnosed relapsing multiple sclerosis (either relapsing-remitting or relapsing secondary progressive multiple sclerosis), and one or more of the following criteria: at least one relapse within the previous year, at least two relapses within the previous 2 years, or at least one active gadolinium-enhancing brain lesion in the 6 mo before screening. Exclusion criteria included a diagnosis of primary progressive multiple sclerosis or a diagnosis of secondary progressive multiple sclerosis without relapse. We used a two-step randomisation process to randomly assign eligible participants (1:1) to two cohorts, then further randomly assign participants in each cohort (1:1:1:1) to four tolebrutinib dose groups (5, 15, 30, and 60 mg administered once daily as an oral tablet). Cohort 1 received tolebrutinib for 12 wk, then matched placebo (ie, identical looking tablets) for 4 wk; cohort 2 received 4 wk of placebo followed by 12 wk of tolebrutinib. Participants and investigators were masked for dose and tolebrutinib-placebo administration sequence; investigators, study team members, and study participants did not have access to unmasked data. MRI scans were done at screening and every 4 wk over 16 wk. The primary efficacy endpoint was the number of new gadolinium-enhancing lesions detected on the scan done after 12 wk of tolebrutinib treatment (assessed at week 12 for cohort 1 and week 16 for cohort 2), relative to the scan done 4 wk previously, and compared with the lesions accumulated during 4 wk of placebo run-in period in cohort 2. Efficacy data were analyzed in a modified intention-to-treat population, using a two-step multiple comparison procedure with modeling anal. Safety was assessed for all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03889639), EudraCT (2018-003927-12), and WHO (U1111-1220-0572), and has been completed. Between May 14, 2019, and Jan 2, 2020, we enrolled and randomly assigned 130 participants to tolebrutinib: 33 to 5 mg, 32 to 15 mg, 33 to 30 mg, and 32 to 60 mg. 129 (99) completed the treatment regimen and 126 were included in the primary anal. At treatment week 12, there was a dose-dependent reduction in the number of new gadolinium-enhancing lesions (mean [SD] lesions per patient: placebo, 1·03 [2·50]; 5 mg, 1·39 [3·20]; 15 mg, 0·77 [1·48]; 30 mg, 0·76 [3·31]; 60 mg, 0·13 [0·43]; p=0·03). One serious adverse event was reported (one patient in the 60 mg group was admitted to hospital because of a multiple sclerosis relapse). The most common non-serious adverse event during tolebrutinib treatment was headache (in one [3] of 33 in the 5 mg group; three [9] of 32 in the 15 mg group; one [3] of 33 in the 30 mg group; and four [13] of 32 in the 60 mg group). No safety-related discontinuations or treatment-related deaths occurred.12 wk of tolebrutinib treatment led to a dose-dependent reduction in new gadolinium-enhancing lesions, the 60 mg dose being the most efficacious, and the drug was well tolerated. Reduction of acute inflammation, combined with the potential to modulate the immune response within the CNS, provides a scientific rationale to pursue phase 3 clin. trials of tolebrutinib in patients with relapsing and progressive forms of multiple sclerosis.Sanofi.

Lancet Neurology 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, Recommanded Product: (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

Takahashi, Yusuke published the artcileSynthesis of Biaryls Having a Piperidylmethyl Group Based on Space Integration of Lithiation, Borylation, and Suzuki-Miyaura Coupling, Safety of 1-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperidine, the publication is European Journal of Organic Chemistry (2020), 2020(5), 618-622, database is CAplus.

In a flow microreactor, aryllithiums bearing a piperidylmethyl group were generated using nBuLi by precise residence time control and effective temperature control, and then selectively borylated with boronic esters such as 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (BpinOiPr) and tri-Me borate B(OMe)₃ by fast mixing. Moreover, the direct integration with Suzuki-Miyaura cross coupling were successfully achieved to obtain nitrogen-containing biaryl compounds The present method could be applied for the straightforward synthesis of the key intermediate of a bioactive component bearing a piperidylmethyl-biphenyl framework.

European Journal of Organic 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 C13H16O2, Safety of 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