Tag: 200-300

《Synthesis and pharmacological evaluation of enantiomerically pure endo-configured KOR agonists with 2-azabicyclo[3.2.1]octane scaffold》 was published in Organic & Biomolecular Chemistry in 2021. These research results belong to Jonas, Hendrik; Aiello, Daniele; Frehland, Bastian; Lehmkuhl, Kirstin; Schepmann, Dirk; Koehler, Jens; Diana, Patrizia; Wuensch, Bernhard. Recommanded Product: (S)-1-tert-Butyl 2-ethyl 4-oxopiperidine-1,2-dicarboxylate The article mentions the following:

Conformationally restricted bicyclic KOR agonists 10 with an endo-configured amino moiety were synthesized to analyze the bioactive conformation of conformationally flexible KOR agonists such as 2-5. A seven-step synthesis starting with (S)-configured 4-oxopiperidine-2-carboxylate 13 was developed. cis- and trans-configured diesters 12 were obtained in a 3 : 1 ratio via hydrogenation of the α,β-unsaturated ester 14. After establishment of the bicyclic scaffold, a diastereoselective reductive amination of ketone 11 provided exclusively the endo-configured bicyclic amines 10a,b. The 3 : 1 mixtures of enantiomers were separated by chiral HPLC, resp., leading to enantiomerically pure KOR agonists (1S,5S,7R)-10a,b and (1R,5R,7S)-10a,b (ent-10a,b). The KOR affinity was determined in receptor binding studies with the radioligand [3H]U-69 593. The high KOR affinity of endo-configured amines 10a (Ki = 7 nM) and 10b (Ki = 13 nM) indicates that the dihedral angle of the KOR pharmacophoric element N(pyrrolidine)-C-C-N(phenylacetyl) of 42° is close to the bioactive conformation of more flexible KOR agonists. It should be noted that changing the configuration of potent and selective KOR agonists 10a and 10b led to potent and selective σ1 ligands (e.g. ent-10aKi(σ1) = 10 nM). The experimental process involved the reaction of (S)-1-tert-Butyl 2-ethyl 4-oxopiperidine-1,2-dicarboxylate(cas: 180854-44-8Recommanded Product: (S)-1-tert-Butyl 2-ethyl 4-oxopiperidine-1,2-dicarboxylate)

(S)-1-tert-Butyl 2-ethyl 4-oxopiperidine-1,2-dicarboxylate(cas: 180854-44-8) 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.Recommanded Product: (S)-1-tert-Butyl 2-ethyl 4-oxopiperidine-1,2-dicarboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Studies on synthesis and anticancer activity of selected N-(2-fluoroethyl)-N-nitrosoureas》 was published in Journal of Medicinal Chemistry in 1984. These research results belong to Johnston, Thomas P.; Kussner, Conrad L.; Carter, Ronald L.; Frye, Jerry L.; Lomax, Nancita R.; Plowman, Jacqueline; Narayanan, V. L.. Recommanded Product: Benzyl (2,6-dioxopiperidin-3-yl)carbamate The article mentions the following:

Aminolysis of FCH2CH2N(NO)CO2C6H4NO2-2 with H2NCH2CH2OH, 1α,2β,3α-2-amino-1,3-cyclohexanediol, cis-1,2-aminocyclohexanol, and 2-amino-2-deoxy-D-glucose gave the corresponding H2O-sol ureas, e.g., I. The H2O-insoluble glutarimide analog II was prepared by nitrosation of the corresponding urea. In trials with B16 melanoma and Lewis lung carcinoma the compounds were comparable to their Cl analogs as inhibitors; I seemed to be the most effective. In the experimental materials used by the author, we found Benzyl (2,6-dioxopiperidin-3-yl)carbamate(cas: 24666-55-5Recommanded Product: Benzyl (2,6-dioxopiperidin-3-yl)carbamate)

Benzyl (2,6-dioxopiperidin-3-yl)carbamate(cas: 24666-55-5) belongs to anime. In organic chemistry, amines are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (NH3), wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group (these may respectively be called alkylamines and arylamines; amines in which both types of substituent are attached to one nitrogen atom may be called alkylarylamines).Recommanded Product: Benzyl (2,6-dioxopiperidin-3-yl)carbamate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Quality Control of tert-Butyl 4-hydroxypiperidine-1-carboxylateIn 2020 ,《Structure-Activity Relationship for the Oxadiazole Class of Antibacterials》 was published in ACS Medicinal Chemistry Letters. The article was written by Boudreau, Marc A.; Ding, Derong; Meisel, Jayda E.; Janardhanan, Jeshina; Spink, Edward; Peng, Zhihong; Qian, Yuanyuan; Yamaguchi, Takao; Testero, Sebastian A.; O’Daniel, Peter I.; Leemans, Erika; Lastochkin, Elena; Song, Wei; Schroeder, Valerie A.; Wolter, William R.; Suckow, Mark A.; Mobashery, Shahriar; Chang, Mayland. The article contains the following contents:

A structure-activity relationship (SAR) for the oxadiazole class of antibacterials was evaluated by syntheses of 72 analogs and determination of the minimal-inhibitory concentrations (MICs) against the ESKAPE panel of bacteria. Selected compounds were further evaluated for in vitro toxicity, plasma protein binding, pharmacokinetics (PK), and a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) infection. Oxadiazole 72c shows potent in vitro antibacterial activity, exhibits low clearance, a high volume of distribution, and 41% oral bioavailability, and shows efficacy in mouse models of MRSA infection. In the experiment, the researchers used tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Quality Control of tert-Butyl 4-hydroxypiperidine-1-carboxylate)

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.Quality Control of tert-Butyl 4-hydroxypiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylateIn 2019 ,《Design, synthesis, cytotoxicity and 3D-QSAR analysis of new 3,6-disubstituted-1,2,4,5-tetrazine derivatives as potential antitumor agents》 appeared in Arabian Journal of Chemistry. The author of the article were Canete-Molina, Alvaro; Espinosa-Bustos, Christian; Gonzalez-Castro, Marcos; Faundez, Mario; Mella, Jaime; Tapia, Ricardo A.; Cabrera, Alan R.; Brito, Ivan; Aguirre, Adam; Salas, Cristian O.. The article conveys some information:

Two new series of 3-substituted-6-(2,5-dimethylpyrazol-1-yl)-1,2,4,5-tetrazines I [Ar = Ph, 3,5-dimethylphenyl, 2-naphthyl, etc.] and II [R = Ph, 4-NO2-C6H4, 2-pyridyl, etc.], and analyzed them for a potential role as antitumor agents were reported. Twenty-two compounds were obtained, and four mol. structures were determined by X-ray diffraction anal. Using flow cytometry and MTT assay, potential action on cell toxicity was determined for each of the compounds for four cancer cell lines. The potency and selectivity demonstrated by these compounds were dependent on the cancer cell line, where the following compounds were found the most promising agents against certain cell lines: compounds I [Ar = 2-naphthyl, 3-chlorophenyl] for HL-60 cells, and I [Ar = Ph, 3,5-dimethylphenyl] on HCT116 cells, I [Ar = 4-CN-C6H4] on Hela cells and II [R = 2-(3-trifluoromethyl)pyridyl] on H1975 cells. The action exerted by these compounds was comparable to the well-known cancer treatment drug etoposide and higher than vatalanib. To arrive at the structural requirements for activity on each cell line, a SAR and 3D-QSAR anal. was carried out. From the 3D-QSAR models, steric and electronic features were identified in the aromatic centers, and were key components for cytotoxic activity on HL-60 cell lines. The cytometry results suggested that some tetrazine derivatives induced apoptosis on HCT116 cells. In addition to this study using tert-Butyl 4-aminopiperidine-1-carboxylate, there are many other studies that have used tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate) was used in this study.

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Primary amines having a tertiary alkyl group (R3CNH2) are difficult to prepare with most methods but are made industrially by the Ritter reaction. In this method a tertiary alcohol reacts with hydrogen cyanide (HCN) in the presence of a concentrated strong acid; a formamide, RNH―CHO, is formed first, which then undergoes hydrolysis.Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Liu, Wenwu; Liu, Xin; Liu, Wenjie; Gao, Yaping; Wu, Limeng; Huang, Yaoguang; Chen, Huanhua; Li, Deping; Zhou, Lijun; Wang, Nan; Xu, Zihua; Jiang, Xiaowen; Zhao, Qingchun published an article in 2022. The article was titled 《Discovery of novel β-carboline derivatives as selective AChE inhibitors with GSK-3β inhibitory property for the treatment of Alzheimer’s disease》, and you may find the article in European Journal of Medicinal Chemistry.Electric Literature of C10H20N2O2 The information in the text is summarized as follows:

The natural product harmine, a representative β-carboline alkaloid from the seeds of Peganum harmala L. (Zygophyllaceae), possesses a broad spectrum of biol. activities. In this study, a novel series of harmine derivatives containing N-benzylpiperidine moiety were identified for the treatment of Alzheimer’s disease (AD). The results showed that all the derivatives possessed significant anti-acetylcholinesterase (AChE) activity and good selectivity over butyrylcholinesterase (BChE). In particular, compound ZLWH-23 exhibited potent anti-AChE activity (IC50 = 0.27μM) and selective BChE inhibition (IC50 = 20.82μM), as well as acceptable glycogen synthase kinase-3 (GSK-3β) inhibition (IC50 = 6.78μM). Mol. docking studies and mol. dynamics simulations indicated that ZLWH-23 could form stable interaction with AChE and GSK-3β. Gratifyingly, ZLWH-23 exhibited good selectivity for GSK-3β over multi-kinases and very low cytotoxicity towards SH-SY5Y, HEK-293T, HL-7702, and HepG2 cell lines. Importantly, ZLWH-23 displayed efficient reduction against tau hyperphosphorylation on Ser-396 site in Tau (P301L) 293T cell model. Collectively, harmine-based derivatives could be considered as possible drug leads for the development of AD therapies. The results came from multiple reactions, including the reaction of 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

Safety of (R)-1-tert-Butyl 3-ethyl piperidine-1,3-dicarboxylateOn September 25, 2006 ,《Asymmetric hydrogenation of pyridines: enantioselective synthesis of nipecotic acid derivatives》 was published in European Journal of Organic Chemistry. The article was written by Lei, Aiwen; Chen, Mao; He, Minsheng; Zhang, Xumu. The article contains the following contents:

An asym. hydrogenation process of 3-substituted pyridine derivatives has been developed with the use of a Rh-TangPhos complex as the catalyst. The whole process consists of an efficient partial hydrogenation of nicotinate and a subsequent highly enantioselective, Rh-catalyzed, homogeneous hydrogenation. A series of chiral nipecotic acid derivatives have been synthesized.(R)-1-tert-Butyl 3-ethyl piperidine-1,3-dicarboxylate(cas: 194726-40-4Safety of (R)-1-tert-Butyl 3-ethyl piperidine-1,3-dicarboxylate) was used in this study.

(R)-1-tert-Butyl 3-ethyl piperidine-1,3-dicarboxylate(cas: 194726-40-4) 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.Safety of (R)-1-tert-Butyl 3-ethyl piperidine-1,3-dicarboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Application of 118511-81-2On May 23, 2013, Mattsson, Cecilia; Andreasson, Theresa; Waters, Nicholas; Sonesson, Clas published an article in Journal of Medicinal Chemistry. The article was 《Systematic in Vivo Screening of a Series of 1-Propyl-4-arylpiperidines against Dopaminergic and Serotonergic Properties in Rat Brain: A Scaffold-Jumping Approach [Erratum to document cited in CA157:687548]》. The article mentions the following:

Tables 1 through 3, Figure 2, and Figure 4 contained an incorrect structure for compound 14; the corrected structure and several related corrections to the text and Supporting Information are provided. On page 9741, lines 23-30, 31, and 34 of the right hand column contained incorrect text; the corrected text is given. The experimental part of the paper was very detailed, including the reaction process of 1-(Piperidin-4-yl)-1H-indole(cas: 118511-81-2Application of 118511-81-2)

1-(Piperidin-4-yl)-1H-indole(cas: 118511-81-2) belongs to piperidines. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions. Application of 118511-81-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Straightforward access to N-trifluoromethyl amides, carbamates, thiocarbamates and ureas》 was written by Scattolin, Thomas; Bouayad-Gervais, Samir; Schoenebeck, Franziska. HPLC of Formula: 87120-72-7This research focused ontrifluoromethyl amide carbamate thiocarbamate ureas. The article conveys some information:

Amides and related carbonyl derivatives are of central importance across the phys. and life sciences1,2. As a key biol. building block, the stability and conformation of amides affect the structures of peptides and proteins as well as their biol. function. In addition, amide-bond formation is one of the most frequently used chem. transformations3,4. Given their ubiquity, a technol. that is capable of modifying the fundamental properties of amides without compromising on stability may have considerable potential in pharmaceutical, agrochem. and materials science. In order to influence the phys. properties of organic mols.-such as solubility, lipophilicity, conformation, pKa and (metabolic) stability-fluorination approaches have been widely adopted5-7. Similarly, site-specific modification with isosteres and peptidomimetics8, or in particular by N-methylation9, has been used to improve the stability, phys. properties, bioactivities and cellular permeabilities of compounds However, the N-trifluoromethyl carbonyl motif-which combines both N-methylation and fluorination approaches-has not yet been explored, owing to a lack of efficient methodol. to synthesize it. Here the authors report a straightforward method to access N-trifluoromethyl analogs of amides and related carbonyl compounds The strategy relies on the operationally simple preparation of bench-stable carbamoyl fluoride building blocks, which can be readily diversified to the corresponding N-CF3 amides, carbamates, thiocarbamates and ureas. This method tolerates rich functionality and stereochem., and the authors present numerous examples of highly functionalized compounds-including analogs of widely used drugs, antibiotics, hormones and polymer units. The results came from multiple reactions, including the reaction of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7HPLC of Formula: 87120-72-7)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Amines can be classified according to the nature and number of substituents on nitrogen. Aliphatic amines contain only H and alkyl substituents. Aromatic amines have the nitrogen atom connected to an aromatic ring.Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine (NClH2).HPLC of Formula: 87120-72-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Convenient, benign and scalable synthesis of 2- and 4-substituted benzylpiperidines》 was written by Agai, Bela; Proszenyak, Agnes; Tarkanyi, Gabor; Vida, Laszlo; Faigl, Ferenc. Electric Literature of C13H20ClNO And the article was included in European Journal of Organic Chemistry on August 27 ,2004. The article conveys some information:

A short, scalable and environmentally benign synthesis of 2- and 4-substituted benzylpiperidines, e.g. I, has been developed. The method is based on the temperature-programmed consecutive deoxygenation and heteroaromatic ring saturation of aryl(pyridin-2-yl)- and aryl(pyridin-4-yl)methanols and aryl(pyridin-4-yl)methanones in the presence of Pd/C catalyst. The crucial roles of the temperature, the acidity and the substrate structure in the change of selectivity have been demonstrated by isolation of several substituted aryl(piperidine)methanols. The carbinols and ketones were prepared from com. available pyridinecarbaldehydes or 4-cyanopyridine and substituted bromobenzenes via organometallic intermediates. The results came from multiple reactions, including the reaction of 4-(3-Methoxybenzyl)piperidine hydrochloride(cas: 149986-58-3Electric Literature of C13H20ClNO)

4-(3-Methoxybenzyl)piperidine hydrochloride(cas: 149986-58-3) belongs to piperidines. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions. Electric Literature of C13H20ClNO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Cox, Christopher D.; Coleman, Paul J.; Breslin, Michael J.; Whitman, David B.; Garbaccio, Robert M.; Fraley, Mark E.; Buser, Carolyn A.; Walsh, Eileen S.; Hamilton, Kelly; Schaber, Michael D.; Lobell, Robert B.; Tao, Weikang; Davide, Joseph P.; Diehl, Ronald E.; Abrams, Marc T.; South, Vicki J.; Huber, Hans E.; Torrent, Maricel; Prueksaritanont, Thomayant; Li, Chunze; Slaughter, Donald E.; Mahan, Elizabeth; Fernandez-Metzler, Carmen; Yan, Youwei; Kuo, Lawrence C.; Kohl, Nancy E.; Hartman, George D. published an article in Journal of Medicinal Chemistry. The title of the article was 《Kinesin Spindle Protein (KSP) Inhibitors. 9. Discovery of (2S)-4-(2,5-Difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (MK-0731) for the Treatment of Taxane-Refractory Cancer》.Recommanded Product: 405057-75-2 The author mentioned the following in the article:

Inhibition of kinesin spindle protein (KSP) is a novel mechanism for treatment of cancer with the potential to overcome limitations associated with currently employed cytotoxic agents. Herein, we describe a C2-hydroxymethyl dihydropyrrole KSP inhibitor (11) that circumvents hERG channel binding and poor in vivo potency, issues that limited earlier compounds from our program. However, introduction of the C2-hydroxymethyl group caused 11 to be a substrate for cellular efflux by P-glycoprotein (Pgp). Utilizing knowledge garnered from previous KSP inhibitors, we found that β-fluorination modulated the pKa of the piperidine nitrogen and reduced Pgp efflux, but the resulting compound (14) generated a toxic metabolite in vivo. Incorporation of fluorine in a strategic, metabolically benign position by synthesis of an N-methyl-3-fluoro-4-(aminomethyl)piperidine urea led to compound 30 that has an optimal in vitro and metabolic profile. Compound 30 (MK-0731) was recently studied in a phase I clin. trial in patients with taxane-refractory solid tumors. The experimental part of the paper was very detailed, including the reaction process of 1-Cbz-4-Methylaminopieridine(cas: 405057-75-2Recommanded Product: 405057-75-2)

1-Cbz-4-Methylaminopieridine(cas: 405057-75-2) belongs to anime. To avoid the problem of multiple alkylation, methods have been devised for “blocking” substitution so that only one alkyl group is introduced. The Gabriel synthesis is one such method; it utilizes phthalimide, C6H4(CO)2NH, whose one acidic hydrogen atom has been removed upon the addition of a base such as KOH to form a salt.Recommanded Product: 405057-75-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem