Category: piperidines

Liu, Gang; Campbell, Brian T.; Holladay, Mark W.; Ford Pulido, Julia M.; Hua, Helen; Gitnick, Dana; Gardner, Michael F.; James, Joyce; Breider, Mike A.; Brigham, Daniel; Belli, Barbara; Armstrong, Robert C.; Treiber, Daniel K. published their research in ACS Medicinal Chemistry Letters on December 13 ,2012. The article was titled 《Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases》.Quality Control of 1-Cyclopropylpiperidin-4-ol The article contains the following contents:

A series of potent, selective platelet-derived growth factor receptor-family kinase inhibitors was optimized starting from a globally selective lead mol. 4 through structural modifications aimed at improving the physiochem. and pharmacokinetic properties, as exemplified by 18b. Further clearance reduction via per-methylation of the α-carbons of a solubilizing piperidine nitrogen resulted in advanced leads 22a and 22b. Results from a mouse tumor xenograft, a collagen-induced arthritis model, and a 7 day rat in vivo tolerability study culminated in the selection of compound 22b (AC710) as a preclin. development candidate. In the experiment, the researchers used 1-Cyclopropylpiperidin-4-ol(cas: 851847-62-6Quality Control of 1-Cyclopropylpiperidin-4-ol)

1-Cyclopropylpiperidin-4-ol(cas: 851847-62-6) belongs to piperidines. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions. Quality Control of 1-Cyclopropylpiperidin-4-ol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Huang, Xixian; Zhu, Nengwu; Wei, Xiaorong; Ding, Yang; Ke, Yixin; Wu, Pingxiao; Liu, Zehua published their research in Journal of Hazardous Materials on December 5 ,2020. The article was titled 《Mechanism Insight into Efficient Peroxydisulfate activation by Novel Nano Zero-valent Iron Anchored yCo3O4 (nZVI/yCo3O4) Composites》.SDS of cas: 826-36-8 The article contains the following contents:

Novel nano zero-valent iron anchored bio-matrix supported Co3O4 (nZVI/yCo3O4) composites were fabricated for tetracycline (TC) efficient degradation by activating peroxydisulfate (PS). The systematical characterizations verified that the nZVI/yCo3O4 composites with magnetism have higher surface area than yCo3O4 and pure Co3O4, contributing to more accessible active sites. Various catalytic parameters (nZVI mass ratio, leached ions, initial pH, catalyst dosage, PS concentration and coexisting anions) were thoroughly investigated. In nZVI/yCo3O4/PS system, 97.6%, 93.4% and 77.3% TC were degraded within 15 min at pH 3.0, 6.0 and 9.0, resp. Based on four successive degradation runs, the excellent mineralization rate and reusability of nZVI/yCo3O4 composites were mainly benefited from the suppressed metals leaching. The PS activated mechanisms were proposed as non-radicals (1O2) dominated pattern at acidic conditions and radicals (SO•-4) predominant pattern at alk. environment, which may be highly related to the electron donating capacity of nZVI at different pH and the M(n+1)+/Mn+ redox cycling between Fe or Co metal. The plausible degradation routes of TC were presented based on the detected intermediates. Overall, the synthesized heterogeneous nZVI/yCo3O4 composites can efficiently active PS at a wide pH range, and further broaden the application of Co-based catalysts in PS activation. After reading the article, we found that the author used Triacetonamine(cas: 826-36-8SDS of cas: 826-36-8)

Triacetonamine(cas: 826-36-8) 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: 826-36-8

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Bey, Philippe; Vevert, Jean Paul published their research in Journal of Organic Chemistry on August 1 ,1980. The article was titled 《Stereospecific alkylation of the Schiff base ester of alanine with 2-substituted-(E)- and -(Z)-vinyl bromides. An efficient synthesis of 2-methyl-(E)-3,4-didehydroglutamic acid, a potent substrate-induced irreversible inhibitor of L-glutamate-1-decarboxylase》.HPLC of Formula: 24666-55-5 The article contains the following contents:

Vinylation of PhCH:NCHMeCO2Me (I) by (E)- or (Z)-RCH:CHBr (R = CO2Me, CONH2, CN) in THF containing LiN(CHMe2)2 proceeded stereospecifically to give RCH:CHCMe(N:CHPh)CO2Me with retention of configuration of the double bond. Thus, I was vinylated with (E)-MeO2CCH:CHBr to give (E)-MeO2CCH:CHCMe(N:CHPh)CO2Me, which was hydrolyzed by aqueous HCl for 24 h at 60° to give the title dehydroglutamic acid. In the experimental materials used by the author, we found Benzyl (2,6-dioxopiperidin-3-yl)carbamate(cas: 24666-55-5HPLC of Formula: 24666-55-5)

Benzyl (2,6-dioxopiperidin-3-yl)carbamate(cas: 24666-55-5) belongs to anime. Nitrous acid converts secondary amines (aliphatic or aromatic) to N-nitroso compounds (nitrosamines): R2NH + HNO2 → R2N―NO. Some nitrosamines are potent cancer-inducing substances, and their possible formation is a serious consideration when nitrites, which are salts of nitrous acid, are present in foods or pharmaceutical preparations. Tertiary amines give rise to nitrosamines more slowly; an alkyl group is eliminated as an aldehyde or ketone, along with nitrous oxide, N2O.HPLC of Formula: 24666-55-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Reference of 2-(Piperidin-4-yl)ethanolIn 2012 ,《Synthesis and structure-activity relationship of fused-pyrimidine derivatives as a series of novel GPR119 agonists》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Negoro, Kenji; Yonetoku, Yasuhiro; Moritomo, Ayako; Hayakawa, Masahiko; Iikubo, Kazuhiko; Yoshida, Shigeru; Takeuchi, Makoto; Ohta, Mitsuaki. The article conveys some information:

A series of fused-pyrimidine derivatives has been discovered as potent and orally active GPR119 agonists. A combination of the fused-pyrimidine structure and 4-chloro-2,5-difluorophenyl group provided the 5,7-dihydrothieno[3,4-d]pyrimidine 6,6-dioxide derivative I as a highly potent GPR119 agonist. Further optimization of the amino group at the 4-position in the pyrimidine ring led to the identification of 2-{1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxido-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl]piperidin-4-yl}acetamide (II) as an advanced analog. Compound II was found to have extremely potent agonistic activity and improved glucose tolerance at 0.1 mg/kg po in mice. The authors consider compound II and its analogs to have clear utility in exploring the practicality of GPR119 agonists as potential therapeutic agents for the treatment of type 2 diabetes mellitus. In the experiment, the researchers used 2-(Piperidin-4-yl)ethanol(cas: 622-26-4Reference of 2-(Piperidin-4-yl)ethanol)

2-(Piperidin-4-yl)ethanol(cas: 622-26-4) have been used as an intermediate in the synthetic preparation of cellular-active allosteric inhibitors of FAKReference of 2-(Piperidin-4-yl)ethanol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Recommanded Product: 87120-72-7In 2021 ,《2,4,5-Trisubstituted Pyrimidines as Potent HIV-1 NNRTIs: Rational Design, Synthesis, Activity Evaluation, and Crystallographic Studies》 appeared in Journal of Medicinal Chemistry. The author of the article were Kang, Dongwei; Ruiz, Francesc X.; Sun, Yanying; Feng, Da; Jing, Lanlan; Wang, Zhao; Zhang, Tao; Gao, Shenghua; Sun, Lin; De Clercq, Erik; Pannecouque, Christophe; Arnold, Eddy; Zhan, Peng; Liu, Xinyong. The article conveys some information:

There is an urgent unmet medical need for novel human immunodeficiency virus type 1 (HIV-1) inhibitors that are effective against a variety of NNRTI-resistance mutations. We report our research efforts aimed at discovering a novel chemotype of anti-HIV-1 agents with improved potency against a variety of NNRTI-resistance mutations in this paper. Structural modifications of the lead K-5a2 led to the identification of a potent inhibitor 16c. 16c yielded highly potent anti-HIV-1 activities and improved resistance profiles compared with the approved drug etravirine. The co-crystal structure revealed the key role of the water networks surrounding the NNIBP for binding and for resilience against resistance mutations, while suggesting further extension of 16c toward the NNRTI-adjacent site as a lead development strategy. Furthermore, 16c demonstrated favorable pharmacokinetic and safety properties, suggesting the potential of 16c as a promising anti-HIV-1 drug candidate. The experimental process involved the reaction of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Recommanded Product: 87120-72-7)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Aniline, ethanolamines, and several other amines are major industrial commodities used in making rubber, dyes, pharmaceuticals, and synthetic resins and fibres and for a host of other applications. Most of the numerous methods for the preparation of amines may be broadly divided into two groups: (1) chemical reduction (replacement of oxygen with hydrogen atoms in the molecule) of members of several other classes of organic nitrogen compounds and (2) reactions of ammonia or amines with organic compounds.Recommanded Product: 87120-72-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Recommanded Product: 1-Methyl-4-piperidoneIn 2019 ,《Cocrystals and Salts of 3,5-Bis(pyridinylmethylene)piperidin-4-one with Aromatic Poly-Carboxylates and Resorcinols: Influence of Stacking Interactions on Solid-State Luminescence Properties》 appeared in Australian Journal of Chemistry. The author of the article were Das, Debarati; Biradha, Kumar. The article conveys some information:

Two bis-pyridyl-substituted α,β-unsaturated ketones form complexes with carboxylic acids and resorcinol derivatives The neutral acid-acid homosynthon was observed in only one complex out of the five acid-bis-pyridyl containing complexes studied here, while the -COO-···HOOC- synthon is dominant as it was observed in four complexes. The carboxylates self-assembled to form discrete dimeric, anionic, 1-dimensional chains and also exhibited mixed ionic H bonds. However, resorcinol derivatives displayed O-H···N H bonding to form tetrameric aggregates of bis-pyridyl ketone mols. and resp. co-formers, while 3,5-dihydroxy HOBz (DHBA) mols. formed 1-dimensional chains by clipping two mols. of ketones with three DHBA mols. Such clipping by the resorcinol derivatives promoted continuous π-π stacking interactions. Consequently, these materials emitted at higher wavelengths compared with the parent bis-pyridyl-substituted α,β-unsaturated ketones. After reading the article, we found that the author used 1-Methyl-4-piperidone(cas: 1445-73-4Recommanded Product: 1-Methyl-4-piperidone)

1-Methyl-4-piperidone(cas: 1445-73-4) 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.Recommanded Product: 1-Methyl-4-piperidone

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Kang, Dongwei; Sun, Yanying; Feng, Da; Gao, Shenghua; Wang, Zhao; Jing, Lanlan; Zhang, Tao; Jiang, Xiangyi; Lin, Hao; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong published an article in Journal of Medicinal Chemistry. The title of the article was 《Development of Novel Dihydrofuro[3,4-d]pyrimidine Derivatives as HIV-1 NNRTIs to Overcome the Highly Resistant Mutant Strains F227L/V106A and K103N/Y181C》.Product Details of 87120-72-7 The author mentioned the following in the article:

Here, we report the design, synthesis, structure-activity relationship studies, antiviral activity, enzyme inhibition, and druggability evaluation of dihydrofuro[3,4-d]pyrimidine derivatives as a potent class of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Compounds 14b (I) (EC50 = 5.79-28.3 nM) and 16c (II) (EC50 = 2.85-18.0 nM) exhibited superior potency against a panel of HIV-1-resistant strains. Especially, for the changeling mutations F227L/V106A and K103N/Y181C, both compounds exhibited remarkably improved activity compared to those of etravirine and rilpivirine. Moreover, 14b and 16c showed moderate RT enzyme inhibition (IC50 = 0.14-0.15 μM), which demonstrated that they acted as HIV-1 NNRTIs. Furthermore, 14b and 16c exhibited favorable pharmacokinetic and safety properties, making them excellent leads for further development. After reading the article, we found that the author used tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Product Details of 87120-72-7)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Milder oxidation, using reagents such as NaOCl, can remove four hydrogen atoms from primary amines of the type RCH2NH2 to form nitriles (R―C≡N), and oxidation with reagents such as MnO2 can remove two hydrogen atoms from secondary amines (R2CH―NHR′) to form imines (R2C=NR′). Tertiary amines can be oxidized to enamines (R2C=CHNR2) by a variety of reagents.Product Details of 87120-72-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Kroth, Heiko; Oden, Felix; Molette, Jerome; Schieferstein, Hanno; Gabellieri, Emanuele; Mueller, Andre; Berndt, Mathias; Sreenivasachary, Nampally; Serra, Andreia Monica; Capotosti, Francesca; Schmitt-Willich, Heribert; Hickman, David; Pfeifer, Andrea; Dinkelborg, Ludger; Stephens, Andrew published an article in 2021. The article was titled 《PI-2620 Lead Optimization Highlights the Importance of Off-Target Assays to Develop a PET Tracer for the Detection of Pathological Aggregated Tau in Alzheimer′s Disease and Other Tauopathies》, and you may find the article in Journal of Medicinal Chemistry.Recommanded Product: 109384-19-2 The information in the text is summarized as follows:

The first candidate PI-2014 was tested in healthy controls and subjects with Alzheimer′s disease (AD). As PI-2014 displayed off-target binding to monoamine oxidase A (MAO-A), a new lead with improved binding to Tau and decreased MAO-A binding was required. For compound optimization, Tau binding assays based on both human AD brain homogenate and Tau-paired helical filaments were employed. Furthermore, two MAO-A screening assays based on (1) human-recombinant MAO-A and (2) displacement of 2-fluoro-ethyl-harmine from mouse brain homogenate were employed. Removing the N-Me group from the tricyclic core resulted in compounds displaying improved Tau binding. For the final round of optimization, the cyclic amine substituents were replaced by pyridine derivatives PI-2620 (2-(2-fluoropyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine) emerged as a best candidate displaying high Tau binding, low MAO-A binding, high brain uptake, and fast and complete brain washout. Furthermore, PI-2620 showed Tau binding on brain sections from corticobasal degeneration, progressive supranuclear palsy, and Pick′s disease. The experimental process involved the reaction of tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Recommanded Product: 109384-19-2)

tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas:109384-19-2) is a 4-hydroxypyridine with a boc protecting group used in the preparation of neurologically active agents and other pharmaceutical compounds.Recommanded Product: 109384-19-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Jin, Tingting; Xu, Lei; Wang, Peipei; Hu, Xiaobei; Zhang, Runyuan; Wu, Zhiqi; Du, Wenxin; Kan, Weijuan; Li, Kun; Wang, Chang; Zhou, Yubo; Li, Jia; Liu, Tao published an article in 2021. The article was titled 《Discovery and Development of a Potent, Selective, and Orally Bioavailable CHK1 Inhibitor Candidate: 5-((4-((3-Amino-3-methylbutyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)picolinonitrile》, and you may find the article in Journal of Medicinal Chemistry.Electric Literature of C10H20N2O2 The information in the text is summarized as follows:

Checkpoint kinase 1 (CHK1) plays an important role in the DNA damage response pathway, being a potential anti-cancer drug target. In this study, we used a strategy for trifluoromethyl substitution to obtain orally bioavailable CHK1 inhibitors to overcome the limitations of lead compound 1, which can only be administered i.v. After detailed investigation, we identified compound 6c as an oral CHK1 inhibitor, which demonstrated a considerably higher plasma exposure in mice. Compound 6c also showed good kinase selectivity. Moreover, it exhibited a significant antiproliferative effect in MV-4-11 cells singly and a synergistic effect in combination with gemcitabine in HT-29, A549, and RPMI-8226 cells. Addnl., compound 6c could inhibit tumor growth in the MV-4-11 xenograft mouse model. The combination of 6c and gemcitabine exhibited synergistic effect in the HT-29 xenograft mouse model. Thus, compound 6c was found to be a selective and oral potential anticancer CHK1 inhibitor. After reading the article, we found that the author used 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. 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.Electric Literature of C10H20N2O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

The author of 《Identification of dihydrofuro[3,4-d]pyrimidine derivatives as novel HIV-1 non-nucleoside reverse transcriptase inhibitors with promising antiviral activities and desirable physicochemical properties》 were Kang, Dongwei; Zhang, Heng; Wang, Zhao; Zhao, Tong; Ginex, Tiziana; Luque, Francisco Javier; Yang, Yang; Wu, Gaochan; Feng, Da; Wei, Fenju; Zhang, Jian; De Clercq, Erik; Pannecouque, Christophe; Chen, Chin Ho; Lee, Kuo-Hsiung; Murugan, N. Arul; Steitz, Thomas A.; Zhan, Peng; Liu, Xinyong. And the article was published in Journal of Medicinal Chemistry in 2019. Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylate The author mentioned the following in the article:

To address drug resistance to HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs), a series of novel diarylpyrimidine (DAPY) derivatives targeting “”tolerant region I”” and “”tolerant region II”” of the NNRTIs binding pocket (NNIBP) were designed utilizing a structure-guided scaffold-hopping strategy. The dihydrofuro[3,4-d]pyrimidine derivatives I and II proved to be exceptionally potent against a wide range of HIV-1 strains carrying single NNRTI-resistant mutations (EC50 = 0.9-8.4 nM), which were remarkably superior to that of etravirine III. Meanwhile, both compounds exhibited comparable activities with III toward the virus with double mutations F227L+V106A and K103N+Y181C. Furthermore, the most active compound I showed favorable pharmacokinetic properties with an oral bioavailability of 30.96% and a half-life of 11.1 h, which suggested that I is worth further investigation as a novel NNRTI to circumvent drug resistance. In the experiment, the researchers used tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylate)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Large quantities of aliphatic amines are made synthetically. The most widely used industrial method is the reaction of alcohols with ammonia at a high temperature, catalyzed by metals or metal oxide catalysts (e.g., nickel or copper). Mixtures of primary, secondary, and tertiary amines are thereby produced.Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem