87120-72-7 | Page 4 of 7 | Heterocyclic Building Blocks-piperidine

Caldwell, Richard D.’s team published research in Journal of Medicinal Chemistry in 2019 | CAS: 87120-72-7

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Acylation is one of the most important reactions of primary and secondary amines; a hydrogen atom is replaced by an acyl group (a group derived from an acid, such as RCOOH or RSO3H, by removal of ―OH, such as RC(=O)―, RS(O)2―, and so on). Reagents may be acid chlorides (RCOC1, RSO2C1), anhydrides ((RCO)2O), or even esters (RCOOR′); the products are amides of the corresponding acids.Safety of tert-Butyl 4-aminopiperidine-1-carboxylate

The author of 《Discovery of Evobrutinib: An Oral, Potent, and Highly Selective, Covalent Bruton’s Tyrosine Kinase (BTK) Inhibitor for the Treatment of Immunological Diseases》 were Caldwell, Richard D.; Qiu, Hui; Askew, Ben C.; Bender, Andrew T.; Brugger, Nadia; Camps, Montserrat; Dhanabal, Mohanraj; Dutt, Vikram; Eichhorn, Thomas; Gardberg, Anna S.; Goutopoulos, Andreas; Grenningloh, Roland; Head, Jared; Healey, Brian; Hodous, Brian L.; Huck, Bayard R.; Johnson, Theresa L.; Jones, Christopher; Jones, Reinaldo C.; Mochalkin, Igor; Morandi, Federica; Nguyen, Ngan; Meyring, Michael; Potnick, Justin R.; Santos, Dusica Cvetinovic; Schmidt, Ralf; Sherer, Brian; Shutes, Adam; Urbahns, Klaus; Follis, Ariele Viacava; Wegener, Ansgar A.; Zimmerli, Simone C.; Liu-Bujalski, Lesley. And the article was published in Journal of Medicinal Chemistry in 2019. Safety of tert-Butyl 4-aminopiperidine-1-carboxylate The author mentioned the following in the article:

Bruton’s tyrosine kinase (BTK) inhibitors such as ibrutinib hold a prominent role in the treatment of B cell malignancies. However, further refinement is needed to this class of agents, particularly in terms of adverse events (potentially driven by kinase promiscuity), which preclude their evaluation in nononcol. indications. Here, we report the discovery and preclin. characterization of evobrutinib, a potent, obligate covalent inhibitor with high kinase selectivity. Evobrutinib displayed sufficient preclin. pharmacokinetic and pharmacodynamic characteristics which allowed for in vivo evaluation in efficacy models. Moreover, the high selectivity of evobrutinib for BTK over epidermal growth factor receptor and other Tec family kinases suggested a low potential for off-target related adverse effects. Clin. investigation of evobrutinib is ongoing in several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus.tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Safety of tert-Butyl 4-aminopiperidine-1-carboxylate) was used in this study.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Villegas, Alondra’s team published research in Journal of Heterocyclic Chemistry in 2022 | CAS: 87120-72-7

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Halogenation, in which one or more hydrogen atoms of an amine is replaced by a halogen atom, occurs with chlorine, bromine, and iodine, as well as with some other reagents, notably hypochlorous acid (HClO). With primary amines the reaction proceeds in two stages, producing N-chloro- and N,N-dichloro-amines, RNHCl and RNCl2, respectively. With tertiary amines, an alkyl group may be displaced by a halogen.Application of 87120-72-7

In 2022,Villegas, Alondra; Satheeshkumar, Rajendran; Ballesteros-Casallas, Andres; Paulino, Margot; Castro, Alejandro; Espinosa-Bustos, Christian; Salas, Cristian O. published an article in Journal of Heterocyclic Chemistry. The title of the article was 《Convergent synthesis, drug target prediction, and docking studies of new 2,6,9-trisubstituted purine derivatives》.Application of 87120-72-7 The author mentioned the following in the article:

A set of new 2,6,9-trisubstituted purine derivatives were designed and synthesized from 6-chloro-2-fluoro-9-alkyl-9H-purine as the key starting material. These purines were synthesized via a multistep protocol and finally subjected to SNAr with various aminopiperidinyl salts. The structures of these compounds were established by substantiating them through spectral techniques like FT-IR, 1H-NMR, 13C-NMR, and 19F-NMR. In addition, for two purine derivatives, a reverse screening strategy based on ligand similarity (PharmMapper web server) resulted in a set of predicted protein target candidates. Interestingly, for both purines, the main potential target candidates belonged to key proteins involved within signaling pathways that are related to proliferation or survival of cancer cells. These proteins correspond mainly to enzymes and specifically kinases. To check if our purines could be ligands for two kinases involved in cancer, docking studies were performed. The results indicated that these purines fitted in the same cavity of crystalized inhibitors. Therefore, in this work we are developed new purine derivatives that could be good inhibitors of some kinases. In the experimental materials used by the author, we found tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Application of 87120-72-7)

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Li, Xing-Zi’s team published research in European Journal of Medicinal Chemistry in 2022 | CAS: 87120-72-7

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.Related Products of 87120-72-7

In 2022,Li, Xing-Zi; Jiang, Shi-You; Li, Guo-Qiang; Jiang, Qian-Ru; Li, Jue-Wan; Li, Chen-Chen; Han, Yu-Qin; Song, Bao-Liang; Ma, Xin-Ran; Qi, Wei; Qiu, Wen-Wei published an article in European Journal of Medicinal Chemistry. The title of the article was 《Synthesis of heterocyclic ring-fused analogs of HMG499 as novel degraders of HMG-CoA reductase that lower cholesterol》.Related Products of 87120-72-7 The author mentioned the following in the article:

HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in cholesterol de novo biosynthesis and its degradation may bring therapeutic benefits for the treatment of cardiovascular disease (CVD) and nonalcoholic steatohepatitis (NASH). Before, we disclosed compound HMG499 (I) as a potent HMGCR degrader, which could be a promising agent for treating CVD, however its side-effect of promoting cholesterol accumulation in cells should be eliminated before progression. Herein, a series of novel heterocyclic ring-fused analogs of HMG499 were synthesized and investigated for their activities of stimulating HMGCR degradation using a HMGCR (TM1-8)-GFP reporting system. Among them, the most active compound 29 (II) (QH536) showed an EC50 of 0.22μM in promoting HMGCR degradation, which was about 2 times more potent than HMG499 (EC50 = 0.43μM). Interestingly, 29 was different from HMG499, it had no side-effect of inducing cholesterol accumulation in cells. Mechanistic studies disclosed that 29 could significantly decrease statin-induced accumulation of HMGCR protein via ubiquitination and degradation of HMGCR through ubiquitin-proteasome pathway and inhibit the cholesterol biosynthesis in cells. Therefore, these heterocyclic ring-fused analogs could be used as promising leads for the development of new types of agents against CVD. Furthermore, 29 also lowered cholesterol levels and suppressed TGFβ1-induced proliferation of LX-2 hepatic stellate cells in a dose-dependent manner. In particular, 29 not only decreased the NASH associated fibrotic mRNA and protein expression of α-SMA, COL1A1, TIMP1 and TGFβ1 but also suppressed cholesterol levels and inflammatory genes of TNF-α, IL-6 an IL-1β in RAW264.7 macrophage cells, indicating that 29 may bring therapeutic benefit to treat NASH. The results came from multiple reactions, including the reaction of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Related Products of 87120-72-7)

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Holman, Samuel D. L.’s team published research in Chemistry – A European Journal in 2022 | CAS: 87120-72-7

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) 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).Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate

In 2022,Holman, Samuel D. L.; Wills, Alfie G.; Fazakerley, Neal J.; Poole, Darren L.; Coe, Diane M.; Berlouis, Leonard A.; Reid, Marc published an article in Chemistry – A European Journal. The title of the article was 《Electrochemical Synthesis of Isoxazolines: Method and Mechanism》.Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate The author mentioned the following in the article:

An electrochem. method for the green and practical synthesis of a broad range of substituted isoxazoline cores is presented. Both aryl and more challenging alkyl aldoximes are converted to the desired isoxazoline in an electrochem. enabled regio- and diastereoselective reaction with electron-deficient alkenes. Addnl., in-situ reaction monitoring methods compatible with electrochem. equipment have been developed in order to probe the reaction pathway. Supporting analyses from kinetic (time-course) modeling and d. functional theory support a stepwise, radical-mediated mechanism, and discounts hypothesised involvement of closed shell [3+2] cycloaddition pathways. The results came from multiple reactions, including the reaction of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate)

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Thu, Zaw Min’s team published research in Bioorganic & Medicinal Chemistry Letters in 2021 | CAS: 87120-72-7

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) 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.Application of 87120-72-7

Thu, Zaw Min; Sun, Jian; Ji, Jingwen; He, Lili; Ji, Jinbo; Iqbal, Zafar; Myo, Ko Ko; Gao, Yuanyu; Zhai, Lijuan; Mu, Yangxiu; Tang, Dong; Vidari, Giovanni; Yang, Haikang; Yang, Zhixiang published an article in 2021. The article was titled 《Synthesis and antibacterial evaluation of new monobactams》, and you may find the article in Bioorganic & Medicinal Chemistry Letters.Application of 87120-72-7 The information in the text is summarized as follows:

Monobactams play an important role in antibiotic drug discovery. Based on the structural characteristics of aztreonam and its biol. targets, six new monobactam derivatives were synthesized and their in vitro antibacterial activities were investigated. Some compounds showed higher activities against tested gram-neg. bacteria than that of parent aztreonam. Monobactam I exhibited the most potent activities, with MIC ranging from 0.25 to 2μg/mL against most bacteria. The experimental part of the paper was very detailed, including the reaction process of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Application of 87120-72-7)

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Thu, Zaw Min’s team published research in Bioorganic & Medicinal Chemistry Letters in 2021 | CAS: 87120-72-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Wang, Ruifeng’s team published research in European Journal of Medicinal Chemistry in 2020 | CAS: 87120-72-7

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Amines have a free lone pair with which they can coordinate to metal centers. Amine–metal bonds are weaker because amines are incapable of backbonding, but they are still important for sensing applications.While stronger than hydrogen bonds, amine–metal bonds are still weaker than both covalent and ionic bonds.Application of 87120-72-7

Application of 87120-72-7In 2020 ,《Design, synthesis, biological evaluation and molecular docking study of novel thieno[3,2-d]pyrimidine derivatives as potent FAK inhibitors》 was published in European Journal of Medicinal Chemistry. The article was written by Wang, Ruifeng; Yu, Sijia; Zhao, Xiangxin; Chen, Yixuan; Yang, Bowen; Wu, Tianxiao; Hao, Chenzhou; Zhao, Dongmei; Cheng, Maosheng. The article contains the following contents:

A series of 2,7-disubstituted thieno[3,2-d]pyrimidine derivatives I [R1 = 2-methoxy, 3-acetyl, 3-methylsulfonyl, etc.], II [R2 = methylcarbamoyl, piperidine-3-carbonylamino, diethoxyphosphorylmethyl, etc.], III [R3 = H, Me, ethoxy, etc.; R4 = H, fluoro, methyl; R5 = H, fluoro] and IV [R6 = pyrrolidin-3-yl, tetrahydro-2H-pyran-4-yl, piperidin-3-ylmethyl, etc.] were synthesized and evaluated as novel focal adhesion kinase (FAK) inhibitors. The novel 2,7-disubstituted thieno[3,2-d]pyrimidine scaffold was designed as a new kinase inhibitor platform that mimics the bioactive conformation of the well-known diaminopyrimidine motif. Most of the compounds potently suppressed the enzymic activities of FAK and potently inhibited the proliferation of U-87MG, A-549 and MDA-MB-231 cancer cell lines. Among these derivatives, the optimized compound III [R3 = R5 = H, R4 = fluoro] potently inhibited the enzyme (IC50 = 28.2 nM) and displayed stronger potency than TAE-226 in U-87MG, A-549 and MDA-MB-231 cells, with IC50 values of 0.16, 0.27, and 0.19μM, resp. Compound III [R3 = R5 = H, R4 = fluoro] also exhibited relatively less cytotoxicity (IC50 = 3.32μM) toward a normal human cell line, HK2. According to the flow cytometry results, compound III [R3 = R5 = H, R4 = fluoro] induced the apoptosis of MDA-MB-231 cells in a dose-dependent manner and effectively arrested MDA-MB-231 cells in G0/G1 phase. Further investigations revealed that compound III [R3 = R5 = H, R4 = fluoro] potently suppressed the migration of MDA-MB-231 cells. Collectively, these data support the further development of compound III [R3 = R5 = H, R4 = fluoro] as a lead compound for FAK-targeted anticancer drug discovery. In the experimental materials used by the author, we found tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Application of 87120-72-7)

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Goldberg, Frederick W.’s team published research in ACS Medicinal Chemistry Letters in 2022 | CAS: 87120-72-7

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Left-handed and right-handed forms (mirror-image configurations, known as optical isomers or enantiomers) are possible when all the substituents on the central nitrogen atom are different (i.e., the nitrogen is chiral). With amines, there is extremely rapid inversion in which the two configurations are interconverted.Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylate

In 2022,Goldberg, Frederick W.; Ting, Attilla K. T.; Beattie, David; Lamont, Gillian M.; Fallan, Charlene; Finlay, M. Raymond V.; Williamson, Beth; Schimpl, Marianne; Harmer, Alexander R.; Adeyemi, Oladipupo B.; Nordell, Par; Cronin, Anna S.; Vazquez-Chantada, Mercedes; Barratt, Derek; Ramos-Montoya, Antonio; Cadogan, Elaine B.; Davies, Barry R. published an article in ACS Medicinal Chemistry Letters. The title of the article was 《Optimization of hERG and Pharmacokinetic Properties for Basic Dihydro-8H-purin-8-one Inhibitors of DNA-PK》.Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylate The author mentioned the following in the article:

Series of neutral DNA-PKcs inhibitors were modified to incorporate a basic group, with the rationale that increasing the volume of distribution while maintaining good metabolic stability should increase the half-life. However, adding a basic group introduced hERG activity and basic compounds with modest hERG activity (IC50 = 10-15μM) prolonged QTc (time from the start of the Q wave to the end of the T wave, corrected by heart rate) in an anesthetized guinea pig cardiovascular model. Further optimization were necessary, including modulation of pKa, to identify I, which combines low hERG activity (IC50 = 75μM) with excellent kinome selectivity and favorable pharmacokinetic properties. In the experiment, the researchers used tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylate)

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Pyta, Krystian’s team published research in European Journal of Medicinal Chemistry in 2019 | CAS: 87120-72-7

Name: tert-Butyl 4-aminopiperidine-1-carboxylateIn 2019 ,《Synthesis, docking and antibacterial studies of more potent amine and hydrazone rifamycin congeners than rifampicin》 was published in European Journal of Medicinal Chemistry. The article was written by Pyta, Krystian; Janas, Anna; Szukowska, Monika; Pecyna, Paulina; Jaworska, Marcelina; Gajecka, Marzena; Bartl, Franz; Przybylski, Piotr. The article contains the following contents:

New rifamycin congeners with incorporated amine and hydrazone substituents leading to lipophilic and/or basic nature and altered rigidity of modified C(3) arm were synthesized and structurally characterized in detail. NMR spectroscopic studies at different temperatures indicate two types of structures of rifamycin congeners that are realized in solution: zwitterionic and non-ionic forms in dependence of the basicity of modified C(3) arm. The presence of rifamycin congeners in these two possible forms has a significant impact on the physico-chem. parameters such as lipophilicity (clogP) and water solubility and different binding mode of the C(3) arm of antibiotic at RNAP binding pocket (mol. target) leading to different antibacterial potency. The highest antibacterial potency against S. aureus (including MRSA and MLSB strains) and S. epidermidis strains, even higher than reference rifampicin and rifaximin antibiotics, was found for rifamycin congeners bearing at the C(3) arm relatively rigid and basic substituents (bipiperidine and guanidine groups). These modifications provide favorable docking mode and excellent water solubility resulting in high potency (MICs 0.0078 μg/mL what gives ∼ 8.5 nM), irresp. whether rifamycin congener is a tertiary amine or hydrazone. In turn, for a higher antibacterial potency of rifamycin congeners against E. faecalis strain (MICs 0.5 μg/mL that is 0.6 μM) as compared to Rif and Rifx, the most crucial factors are: bulkiness and the lipophilic character of the end of the C(3) rebuilt arm. The experimental part of the paper was very detailed, including the reaction process of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Name: tert-Butyl 4-aminopiperidine-1-carboxylate)

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Lee, Kin Sing Stephen’s team published research in Bioorganic & Medicinal Chemistry in 2020 | CAS: 87120-72-7

《Preparation and evaluation of soluble epoxide hydrolase inhibitors with improved physical properties and potencies for treating diabetic neuropathic pain》 was written by Lee, Kin Sing Stephen; Ng, Jen C.; Yang, Jun; Hwang, Sung-Hee; Morisseau, Christophe; Wagner, Karen; Hammock, Bruce D.. Application of 87120-72-7This research focused onurea drug design preparation sEH inhibitor diabetic neuropathic pain; Drug design; Drug target residence time; Inhibitor; Neuropathic pain; Physical properties; Soluble epoxide hydrolase. The article conveys some information:

Soluble epoxide hydrolase (sEH), a novel therapeutic target for neuropathic pain, is a largely cytosolic enzyme that degrades epoxy-fatty acids (EpFAs), an important class of lipid signaling mols. Many inhibitors of sEH have been reported, and to date, the 1,3-disubstituted urea has the highest affinity reported for the sEH among the central pharmacophores evaluated. An earlier somewhat water soluble sEH inhibitor taken to the clinic for blood pressure control had mediocre potency (both affinity and kinetics) and a short in vivo half-life. We undertook a study to overcome these difficulties, but the sEH inhibitors carrying a 1,3-disubstituted urea often suffer poor phys. properties that hinder their formulation. In this report, we described new strategies to improve the phys. properties of sEH inhibitors with a 1,3-disubstituted urea while maintaining their potency and drug-target residence time (a complementary in vitro parameter) against sEH. To our surprise, we identified two structural modifications that substantially improve the potency and phys. properties of sEH inhibitors carrying a 1,3-disubstituted urea pharmacophore. Such improvements will greatly facilitate the movement of sEH inhibitors to the clinic. The experimental part of the paper was very detailed, including the reaction process of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Application of 87120-72-7)

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem