Heterocyclic Building Blocks-piperidine

In 2022,Xue, Ding; Xu, Yibin; Kyani, Armita; Roy, Joyeeta; Dai, Lipeng; Sun, Duxin; Neamati, Nouri published an article in Journal of Medicinal Chemistry. The title of the article was 《Discovery and Lead Optimization of Benzene-1,4-disulfonamides as Oxidative Phosphorylation Inhibitors》.Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate The author mentioned the following in the article:

Inhibition of oxidative phosphorylation (OXPHOS) is a promising therapeutic strategy for select cancers that are dependent on aerobic metabolism Here, we report the discovery, optimization, and structure-activity relationship (SAR) study of a series of novel OXPHOS inhibitors. The hit compound, benzene-1,4-disulfonamide 1 (I), was discovered in a phenotypic screen selective for cytotoxicity in a galactose-containing medium. Our multi-parameter optimization campaign led to the discovery of 65 (DX3-235)(II), showing nanomolar inhibition of complex I function and ATP production in a galactose-containing medium resulting in significant cytotoxicity. Importantly, 64 (DX3-234)(III), a close analog of 65, is well tolerated in mice and shows significant single agent efficacy in a Pan02 syngeneic pancreatic cancer model, suggesting that highly potent and selective OXPHOS inhibitors can be useful for the treatment of pancreatic cancer. In the part of experimental materials, we found many familiar compounds, such as tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Reduction of nitro compounds, RNO2, by hydrogen or other reducing agents produces primary amines cleanly (i.e., without a mixture of products), but the method is mostly used for aromatic amines because of the limited availability of aliphatic nitro compounds. Reduction of nitriles and oximes (R2C=NOH) also yields primary amines.Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Application In Synthesis of 1-Methyl-4-piperidoneIn 2020 ,《Screening and Phenotypical Characterization of Schistosoma mansoni Histone Deacetylase 8 (SmHDAC8) Inhibitors as Multistage Antischistosomal Agents》 was published in ACS Infectious Diseases. The article was written by Saccoccia, Fulvio; Brindisi, Margherita; Gimmelli, Roberto; Relitti, Nicola; Guidi, Alessandra; Saraswati, A. Prasanth; Cavella, Caterina; Brogi, Simone; Chemi, Giulia; Butini, Stefania; Papoff, Giuliana; Senger, Johanna; Herp, Daniel; Jung, Manfred; Campiani, Giuseppe; Gemma, Sandra; Ruberti, Giovina. The article contains the following contents:

Schistosomiasis (also known as bilharzia) is a neglected tropical disease caused by platyhelminths of the genus Schistosoma. The disease is endemic in tropical and subtropical areas of the world where water is infested by the intermediate parasite host, the snail. More than 800 million people live in endemic areas and more than 200 million are infected and require treatment. Praziquantel (PZQ) is the drug of choice for schistosomiasis treatment and transmission control being safe and very effective against adult worms of all the clin. relevant Schistosoma species. Unfortunately, it is ineffective on immature, juvenile worms, therefore it does not prevent reinfection. Moreover, the risk of development and spread of drug resistance strains due to the wide use of a single drug in such a large population represents a serious threat. Therefore, research aimed to identifying novel drugs to be used alone or in combination with PZQ are needed. Histone deacetylase 8 (HDAC8) from the parasite Schistosoma mansoni is a class I zinc-dependent HDAC which is abundantly expressed in all stages of its life cycle, thus representing an interesting target for drug discovery. Through virtual screening and phenotypical characterization of selected hits, the authors discovered two main chem. classes of compounds characterized by the presence of a hydroxamate-based metal binding group coupled to a spiroindoline or a tricyclic thieno[3,2-b]indole core as capping groups. Some of the compounds of both classes were deeply investigated and showed to impair viability of larval, juvenile, and adult schistosomes, to impact egg production in vitro and/or to induce morphol. alterations of the adult schistosome reproductive systems. Noteworthy, all of them inhibit the recombinant form of SmHDAC8 enzyme in vitro. Overall, the authors identified very interesting scaffolds paving the way to the development of effective antischistosomal agents. In the experimental materials used by the author, we found 1-Methyl-4-piperidone(cas: 1445-73-4Application In Synthesis of 1-Methyl-4-piperidone)

1-Methyl-4-piperidone(cas: 1445-73-4) is a member of piperidine. Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Hence, continuous efforts have been made to develop convenient methods to prepare piperidine derivatives.Application In Synthesis of 1-Methyl-4-piperidone

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《3,6-Diamino-7,8-dihydroisoquinoline-4-carbonitrile derivatives: unexpected facile synthesis, full-color-tunable solid-state emissions and mechanofluorochromic activities》 was published in Organic Chemistry Frontiers in 2021. These research results belong to Zhang, Xinyu; Wang, Dan; Shen, Hao; Wang, Shuxian; Zhou, Yunbing; Lei, Yunxiang; Gao, Wenxia; Liu, Miaochang; Huang, Xiaobo; Wu, Huayue. Related Products of 39546-32-2 The article mentions the following:

A series of novel 3,6-diamino-7,8-dihydroisoquinoline-4-carbonitrile (DDIC) derivatives I [R = Bn, R1 = Me; R2 = Ph, 4-FC6H4, 2-thienyl, etc.; RR1 = (CH2)4, (CH2)5, (CH2)2CH(CH3)(CH2)2, etc.] were prepared from dicyanomethylene-4H-pyran derivatives and secondary amines by a mechanism of ring-opening and sequential ring-closing reactions. This reaction had the advantages of readily available materials, simple operations, mild reaction conditions, a broad substrate scope and good yields. The DDIC derivatives displayed solid-state fluorescence with the emission wavelengths covering the whole visible light range and the solid-state emissions were demonstrated to be ascribed to the twisted mol. conformations and loose stacking modes by crystal structural anal. Among the compounds, 9aa exhibited a bathochromic mechanofluorochromic (MFC) phenomenon from blue to cyan due to increased mol. conjugation upon grinding, whereas 3aj and 3ka exhibited hypsochromic MFC activities with the color changing from orange to green and red to orange, resp., because of decreased mol. conjugation, revealing that full-color-tunable emissions could also be realized by mechanofluorochromism. Furthermore, MFC-active mols. could be used in the field of encryption of important image or text information. Addnl., 3ka was demonstrated to emit single-mol. white fluorescence in organic solvents through the regulation of the concentration The unexpected discovery of the DDIC derivatives provided a new possibility for the design and synthesis of novel isoquinoline-based fluorescent materials with excellent performance in the solid state. The experimental process involved the reaction of Piperidine-4-carboxamide(cas: 39546-32-2Related Products of 39546-32-2)

Piperidine-4-carboxamide(cas: 39546-32-2) belongs to anime. Many important products require amines as part of their syntheses. Methylamine is utilized in the production of the analgesic meperidine (trade name Demerol) and the photographic developer Metol (trademark), and dimethylamine is used in the synthesis of the antihistamine diphenhydramine (trade name Benadryl), the solvent dimethylformamide (DMF), and the rocket propellant 1,1-dimethylhydrazine. The synthesis of the insect repellent N,N-diethyl-m-toluamide (DEET) incorporates diethylamine while that of the synthetic fibre Kevlar requires aromatic amines.Related Products of 39546-32-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Enzyme-catalyzed hydrolysis of N-benzyloxycarbonyl-cis-2,6-(acetoxymethyl)piperidine. A facile route to optically active piperidines》 was written by Chenevert, Robert; Dickman, Michael. SDS of cas: 59234-40-1 And the article was included in Tetrahedron: Asymmetry on August 31 ,1992. The article conveys some information:

The first enzymic asymmetrization of a piperidine system is reported. Hydrolysis of N-benzyloxycarbonyl-cis-2,6-(acetoxymethyl)piperidine in the presence of Aspergillus niger lipase gave the corresponding 2R,6S monoacetate in good chem. yield and very high optical purity (ee ≥ 98%). In the experiment, the researchers used many compounds, for example, Cis-piperidine-2,6-dicarboxylic acid(cas: 59234-40-1SDS of cas: 59234-40-1)

Cis-piperidine-2,6-dicarboxylic acid(cas: 59234-40-1) is a member of piperidine. Piperidine is ubiquitous structural motif widely occurred in diverse synthetically and naturally occurring bioactive molecules. Piperidines are an immensely important class of compounds medicinally: the piperidine ring is the most common heterocyclic subunit among FDA approved drugs.SDS of cas: 59234-40-1

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Quality Control of Cis-piperidine-2,6-dicarboxylic acidOn November 30, 1985 ,《The characterization of the specific binding of [3H]-N-acetylaspartylglutamate to rat brain membranes》 appeared in Journal of Neuroscience. The author of the article were Koller, Kerry J.; Coyle, Joseph T.. The article conveys some information:

3H-labeled N-acetylaspartylglutamate (NAAG) [3106-85-2] bound saturably and reversibly to rat brain crude synaptosomal membranes. Optimal binding occurred in Tris-HCl buffer, pH 7.2, at 37°, using previously frozen, preincubated membranes. Saturation experiments revealed an apparent dissociation constant of 383 nm and a Bmax of 31 pmol/mg protein. [3H]NAAG specific binding was displaceable by serine-O-sulfate  [626-69-7], quisqualate  [52809-07-1], ibotenate  [2552-55-8], and glutamate  [56-86-0], with Ki values in the nanomolar range, whereas the amino-phosphono analogs displaced [3H]NAAG in the micromolar range. No specific binding was found in peripheral tissues. Within the central nervous system, the thalamus exhibited the greatest amount of binding, whereas binding was lowest in cortex. Ca2+ enhanced the specific binding, whereas Na+ caused a concentration-dependent inhibition. It appears that [3H]NAAG labels an acidic amino acid receptor site designated A-4, which recognizes the antagonist, 2-amino-4-phosphonobutyric acid, and this receptor may mediate the neurophysiol. effects of endogenous NAAG. After reading the article, we found that the author used Cis-piperidine-2,6-dicarboxylic acid(cas: 59234-40-1Quality Control of Cis-piperidine-2,6-dicarboxylic acid)

Cis-piperidine-2,6-dicarboxylic acid(cas: 59234-40-1) is a member of piperidine. Piperidine-containing compounds are also frequently employed in synthesis as ligands or auxiliaries. Accordingly, many efforts have been devoted to the development of novel methods for the synthesis of these compounds over the years.Quality Control of Cis-piperidine-2,6-dicarboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Safety of Methyl 2-(1-methylpiperidin-4-yl)acetateOn May 3, 1985 ,《Synthetic applications of 2-cyano-1,2,3,6-tetrahydropyridines. 2. Synthesis of isodasycarpidone and related systems, the ervitsine skeleton and its benzo analog》 appeared in Journal of Organic Chemistry. The author of the article were Bosch, Joan; Rubiralta, Mario; Domingo, Antonio; Bolos, Jordi; Linares, Ana; Minguillon, Cristina; Amat, Mercedes; Bonjoch, Josep. The article conveys some information:

The synthesis of isodasycarpidone (I, R = Me, R1 = Et, R2 = H) N-demethylisodasycaripdone (I, R = H, R1 = Et, R2 = H) and their epi derivatives I (R = Me, R1 = H, R2 = Et; R = R1 = H, R2 = Et) is described. The condensation of an appropriate 2-cyano-1,2,3,6-tetrahydropyridine with indole and the conjugate addition of diethylcopper(I) magnesium bromide to the resulting α,β-unsaturated esters constitute the key steps of this synthesis. A similar condensation from methyl-2-cyano-1-methyl-1,2,3,6-tetrahydropyridine-4-acetate and indolylmagnesium iodide or (m-methoxyphenyl)magnesium bromide, followed by catalytic hydrogenation, hydrolysis, and cyclization by polyphosphoric acid establishes synthetic routes to the tetracyclic framework (II) of the indole alkaloid ervitsine and its benzo analog III. The experimental process involved the reaction of Methyl 2-(1-methylpiperidin-4-yl)acetate(cas: 95533-25-8Safety of Methyl 2-(1-methylpiperidin-4-yl)acetate)

Methyl 2-(1-methylpiperidin-4-yl)acetate(cas: 95533-25-8) is a member of piperidine. Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Hence, continuous efforts have been made to develop convenient methods to prepare piperidine derivatives.Safety of Methyl 2-(1-methylpiperidin-4-yl)acetate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Spivak, Charles E.; Waters, James A.; Aronstam, Robert S. published an article in Molecular Pharmacology. The title of the article was 《Binding of semirigid nicotinic agonists to nicotinic and muscarinic receptors》.COA of Formula: C8H15NO2 The author mentioned the following in the article:

Isoarecolone methiodide (1-methyl-4-acetyl-1,2,3,6-tetrahydropyridine methiodide) was previously shown to be among the most potent agonists tested at the frog neuromuscular junction. Because nicotinic receptors from different sources vary in their selectivities, isoarecolone methiodide as well as 19 addnl. congeners, most of which were also previously tested at the frog neuromuscular junction, were studied in binding assays. Torpedo nobiliana was the tissue source for nicotinic receptors. Two types of experiments were conducted. The first evaluated the affinities of the agonists (including acetylcholine and carbamylcholine) for the recognition site by allowing the agonists to compete for that site with 125I-α-bungarotoxin. The inhibition potencies obtained correlated strongly (Spearman’s correlation coefficient, -0.91) with the potency obtained at the frog neuromuscular junction. The second type of experiment evaluated the agonists for their ability to activate the receptor. The binding of [3H]perhydrohistrionicotoxin, which was employed as an indicator of the activation of the receptor, was measured in the presence of each of the agonists. Isoarecolone methiodide was the most potent of all. A few of the agonists (partial agonists) were incapable of fully enhancing this binding. For the full agonists, the concentration that produced half of the maximum binding of [3H]perhydrohistrionicotoxin was defined as the EC50. The correlation coefficient (Spearman’s) for EC50 vs. potency at the frog neuromuscular junction was -0.73, indicating innate differences between Torpedo and frog receptors. In addition, these compounds were treated for their affinity at muscarinic receptors from rat brain. Competition experiments were carried out using [3H]N-methylscopolamine. The affinity of isoarecolone methiodide was only about 7-fold lower than that of acetylcholine and less than 2-fold lower than that of carbamylcholine. In contrast, 1-methyl-4-acetylpiperazine methiodide was much more selective for nicotinic receptors. Its activity was similar to isoarecolone methiodide at the nicotinic receptor, but it was among the weakest compounds in its affinity for the muscarinic receptor. The experimental process involved the reaction of Methyl 1-methylpiperidine-3-carboxylate(cas: 1690-72-8COA of Formula: C8H15NO2)

Methyl 1-methylpiperidine-3-carboxylate(cas: 1690-72-8) is a member of piperidine. Piperidine-containing compounds are also frequently employed in synthesis as ligands or auxiliaries. Accordingly, many efforts have been devoted to the development of novel methods for the synthesis of these compounds over the years.COA of Formula: C8H15NO2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2018,Demuth, Jiri; Kucera, Radim; Kopecky, Kamil; Havlinova, Zuzana; Libra, Antonin; Novakova, Veronika; Miletin, Miroslav; Zimcik, Petr published 《Efficient synthesis of a wide-range absorbing azaphthalocyanine dark quencher and its application to dual-labeled oligonucleotide probes for quantitative real-time polymerase chain reactions》.Chemistry – A European Journal published the findings.Category: piperidines The information in the text is summarized as follows:

Unsym. dialkylamino-substituted zinc azaphthalocyanine (AzaPc) exhibits unique spectral and photophys. properties for dark quenchers of fluorescence in DNA hybridization probes. The panchromatic light absorption of AzaPc from 300 nm up to at least 700 nm and its lack of fluorescence make it an ideal candidate for a universal dark quencher. To prove this exptl., oligodeoxyribonucleotide probes were labeled at the 3′-end by this AzaPc and at the 5′-end by a fluorophore used in the polymerase chain reaction (PCR)-i.e., fluorescein, CAL Fluor Red 610, and Cy5. AzaPc showed a significantly higher quenching efficiency compared to the com. available dark quenchers (BHQ-1, BHQ-2, BBQ-650) in a developed model of TaqMan PCR assay. The AzaPc-labeled probe proved to also be useful in a practical PCR assay for the quantification of the SLCO2B1 transporter gene expression. The constructed calibration curves indicated linearity in the range from 102 to 107 of target copies. After reading the article, we found that the author used 2-(Piperidin-4-yl)ethanol(cas: 622-26-4Category: piperidines)

2-(Piperidin-4-yl)ethanol(cas: 622-26-4) can be used to synthese ursolic acid derivatives, spiroimidazolidinone NPC1L1 inhibitors, neurokinin-2 receptor antagonists, antagonists for inhibition of platelet aggregation.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2019,ACS Central Science included an article by Lee, Kin Sing Stephen; Yang, Jun; Niu, Jun; Ng, Connie J.; Wagner, Karen M.; Dong, Hua; Kodani, Sean D.; Wan, Debin; Morisseau, Christophe; Hammock, Bruce D.. Electric Literature of C10H20N2O2. The article was titled 《Drug-Target Residence Time Affects in Vivo Target Occupancy through Multiple Pathways》. The information in the text is summarized as follows:

The drug discovery and development process is greatly hampered by difficulties in translating in vitro potency to in vivo efficacy. Recent studies suggest that the long-neglected drug-target residence time parameter complements classical drug affinity parameters (KI, Kd, IC50, or EC50) and is a better predictor of in vivo efficacy. Compounds with a long drug-target residence time are often more efficacious in vivo. The impact, however, of the drug-target residence time on in vivo efficacy remains controversial due to difficulties in exptl. determining the in vivo target occupancy during drug treatment. To tackle this problem, an in vivo displacement assay was developed using soluble epoxide hydrolase as a biol. model. In this report, we exptl. demonstrated that drug-target residence time affects the duration of in vivo drug-target binding. In addition, the drug-target residence time plays an important role in modulating the rate of drug metabolism which also affects the efficacy of the drug. In the experimental materials used by the author, we found tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Electric Literature of C10H20N2O2)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. The methylamines occur in small amounts in some plants. Many polyfunctional amines (i.e., those having other functional groups in the molecule) occur as alkaloids in plants—for example, mescaline, 2-(3,4,5-trimethoxyphenyl)ethylamine; the cyclic amines nicotine, atropine, morphine, and cocaine; and the quaternary salt choline, N-(2-hydroxyethyl)trimethylammonium chloride, which is present in nerve synapses and in plant and animal cells.Electric Literature of C10H20N2O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Structure activity relationship analysis of antiproliferative cyclic C5-curcuminoids without DNA binding: Design, synthesis, lipophilicity and biological activity》 was published in Journal of Molecular Structure in 2020. These research results belong to Huber, Imre; Rozmer, Zsuzsanna; Gyongyi, Zoltan; Budan, Ferenc; Horvath, Peter; Kiss, Eszter; Perjesi, Pal. Product Details of 1445-73-4 The article mentions the following:

The chem. susceptibility of the β-diketone linker between the two aromatic rings in the structure of curcumin to hydrolysis and metabolism has made it crucial to investigate structurally modified analogs of curcumin without such shortcomings. The synthesis of twenty cyclic C5-curcuminoids, I (R = NO2, Cl, H, MeO, NMe2, X = CHMe, NH, NMe, CHOH), is described in this study in order to gain more insight into their anticancer structure-activity relationship (SAR). The design of their synthesis included four different cyclanones and five substituted aromatic aldehydes to form four, five-membered subgroups. These model compounds were evaluated in vitro for antiproliferative activity in an XTT cell viability assay against MCF-7 human non-invasive breast adenocarcinoma cancer cells and Jurkat human T lymphocyte leukemia cells in five different concentrations (10 nM, 100 nM, 1μM, 10μM and 20μM). The majority of the compounds investigated have shown remarkable cytotoxicity with IC50 values in the range of 120 nM and 2μM with very high relative toxicity values to curcumin. The SAR conclusions are drawn and summarized. A method was developed and applied in a TLC based exptl. logP measurement, which is new for such C5-curcuminoids. The logP data and structural modifications have shown a strong correlation. The correlation of these exptl. logP and the corresponding IC50 values of the model-compounds were calculated according to the Pearson and Kendall correlation coefficient and showed weak concordance. The physicochem. behaviors of the majority of these compounds are in good accordance with Lipinski’s rule. The most promising compound is I (R = NO2, X = NH), which is the most active (IC50 = 0.12-0.32μM) and most potent (80 times of curcumin) compound with the lowest lipophilicity (exptl. logP = 3.22), which is important also from a pharmacokinetic point of view. The anal. of exptl. logP and computed ClogP values have revealed good agreement. These cyclic C5-curcuminoids in contrast to curcumin do not bind to natural DNA based on their CD spectra. The results came from multiple reactions, including the reaction of 1-Methyl-4-piperidone(cas: 1445-73-4Product Details of 1445-73-4)

1-Methyl-4-piperidone(cas: 1445-73-4) is a member of piperidine. Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Hence, continuous efforts have been made to develop convenient methods to prepare piperidine derivatives.Product Details of 1445-73-4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem