Heterocyclic Building Blocks-piperidine

《Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors》 was published in Journal of Medicinal Chemistry in 2020. These research results belong to Schade, Markus; Merla, Beatrix; Lesch, Bernhard; Wagener, Markus; Timmermanns, Simone; Pletinckx, Katrien; Hertrampf, Torsten. Computed Properties of C10H19NO3 The article mentions the following:

Pharmacol. inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization. In addition to this study using tert-Butyl 4-hydroxypiperidine-1-carboxylate, there are many other studies that have used tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Computed Properties of C10H19NO3) was used in this study.

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.Computed Properties of C10H19NO3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《A Buchwald-Hartwig Protocol to Enable Rapid Linker Exploration of Cereblon E3-Ligase PROTACs**》 was written by Hayhow, Thomas G.; Borrows, Rachel E. A.; Diene, Coura R.; Fairley, Gary; Fallan, Charlene; Fillery, Shaun M.; Scott, James S.; Watson, David W.. Product Details of 622-26-4 And the article was included in Chemistry – A European Journal in 2020. The article conveys some information:

A palladium-catalyzed Buchwald-Hartwig amination for lenalidomide-derived aryl bromides was optimized using high throughput experimentation (HTE) to afford isoindolyl amines I [R1 = H, Me; R2 = n-Bu, Ph, 2-MeC6H4, etc.; R1R2 = (CH2)2O(CH2)2, (CH2)2CH(CH2OH)(CH2)2, (CH2)2N(Boc)(CH2)2, etc.]. The substrate scope of the optimized conditions was evaluated for a range of alkyl- and aryl- amines and functionalised aryl bromides. The methodol. allowed access to new cereblon-based bifunctional proteolysis targeting chimeras with a reduced step count and improved yields. The results came from multiple reactions, including the reaction of 2-(Piperidin-4-yl)ethanol(cas: 622-26-4Product Details of 622-26-4)

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.Product Details of 622-26-4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Zhang, Zhuming; Connolly, Peter J.; Lim, Heng Keang; Pande, Vineet; Meerpoel, Lieven; Teleha, Christopher; Branch, Jonathan R.; Ondrus, Janine; Hickson, Ian; Bush, Tammy; Luistro, Leopoldo; Packman, Kathryn; Bischoff, James R.; Ibrahim, Salam; Parrett, Christopher; Chong, Yolanda; Gottardis, Marco M.; Bignan, Gilles published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Discovery of JNJ-63576253: A Clinical Stage Androgen Receptor Antagonist for F877L Mutant and Wild-Type Castration-Resistant Prostate Cancer (mCRPC)》.Related Products of 109384-19-2 The article contains the following contents:

Persistent androgen receptor (AR) activation drives therapeutic resistance to second-generation AR pathway inhibitors and contributes to the progression of advanced prostate cancer. One resistance mechanism is point mutations in the ligand binding domain of AR that can transform antagonists into agonists. The AR F877L mutation, identified in patients treated with enzalutamide or apalutamide, confers resistance to both enzalutamide and apalutamide. Compound 4 (JNJ-pan-AR) was identified as a pan-AR antagonist with potent activity against wild-type and clin. relevant AR mutations including F877L. Metabolite identification studies revealed a latent bioactivation pathway associated with 4. Subsequent lead optimization of 4 led to amelioration of this pathway and nomination of 5 (JNJ-63576253) as a clin. stage, next-generation AR antagonist for the treatment of castration-resistant prostate cancer (CRPC). The results came from multiple reactions, including the reaction of tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Related Products of 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.Related Products of 109384-19-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Zhou, Yu; Li, Xiaoguang; Chen, Kerong; Ba, Qian; Zhang, Xu; Li, Jingquan; Wang, Jinfang; Wang, Hui; Liu, Hong published their research in European Journal of Medicinal Chemistry in 2021. The article was titled 《Structural optimization and biological evaluation for novel artemisinin derivatives against liver and ovarian cancers》.Application In Synthesis of 2-(Piperidin-4-yl)ethanol The article contains the following contents:

An increasing number of artemisinin (ARS) and its derivatives have been reported for their potential therapeutic value of human cancer. However, their therapeutic potencies are limited owing to their poor pharmacokinetic profiles. Our previous studies showed that lead compound I originated from incorporating the pharmacophore of the approved chemotherapeutic agent melphalan into the basic skeleton of artemisinin with a succinic linker exhibited an excellent toxicity to human ovarian cancer cells and low cytotoxicity to normal cells. The mechanism studies demonstrated that it inhibited the growth and proliferation of ovarian cancer cells and resulted in S-phase arrest, apoptosis and inhibition of migration. Meanwhile, it exhibited excellent antitumor activities in animal models. Herein, further structure optimization for this lead compound I was performed and nineteen novel derivatives were designed and synthesized. Several compounds demonstrated powerful cytotoxic effects against human liver cancer and ovarian cancer cell lines, with their IC50s below 0.86μM against Hep3B and A2780 cell lines, which are superior to that of I. Four compounds were selected to further evaluate their antitumor activities in in vitro and in vivo ovarian and liver cancer models; the results indicated that compound II exhibited the best therapeutic effect, not only effectively inhibiting the growth of 7404 xenograft and Huh7 xenograft, but also presenting a good dose-dependent inhibition toward the growth of A2780 xenograft. Overall, based on these pos. results, these novel chem. structures may provide a new inspiration for the discovery of novel antitumor agents originated from artemisinin scaffolds.2-(Piperidin-4-yl)ethanol(cas: 622-26-4Application In Synthesis of 2-(Piperidin-4-yl)ethanol) was used in this study.

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.Application In Synthesis of 2-(Piperidin-4-yl)ethanol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Nguyen, Huy H.; Tahirovic, Yesim A.; Truax, Valarie M.; Wilson, Robert J.; Jecs, Edgars; Miller, Eric J.; Kim, Michelle B.; Akins, Nicholas S.; Xu, Lingjie; Jiang, Yi; Wang, Tao; Sum, Chi S.; Cvijic, Mary E.; Schroeder, Gretchen M.; Wilson, Lawrence J.; Liotta, Dennis C. published an article in 2021. The article was titled 《Amino-Heterocycle Tetrahydroisoquinoline CXCR4 Antagonists with Improved ADME Profiles via Late-Stage Buchwald Couplings》, and you may find the article in ACS Medicinal Chemistry Letters.COA of Formula: C10H20N2O2 The information in the text is summarized as follows:

This work surveys a variety of diamino-heterocycles as an isosteric replacement for the piperazine substructure of our previously disclosed piperarinyl-tetrahydroisoquinoline containing CXCR4 antagonists. A late-stage Buchwald coupling route was developed for rapid access to final compounds from com. building blocks. Among 13 analogs in this study, compound 31 (I) embodying an aza-piperazine linkage was found to have the best overall profile with potent CXCR4 inhibitory activity and favorable in vitro absorption, distribution, metabolism, and excretion (ADME) properties. An anal. of the calculated physiochem. parameters (ROF, cLogD) and the exptl. ADME attributes of the analogs lead to the selection of 31 for pharmacokinetic studies in mice. Compared with the clin. compound AMD11070, compound 31 has no CYP450 3A4 or 2D6 inhibition, higher metabolic stability and PAMPA permeability, greatly improved physiochem. parameters, and superior oral bioavailability (%F = 24). A binding rationale for 31 within CXCR4 was elucidated from docking and mol. simulation studies. The experimental process involved the reaction of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7COA of Formula: C10H20N2O2)

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).COA of Formula: C10H20N2O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Xu, Xi; Chang, Xiujin; Huang, Jingxuan; Zhang, Di; Wang, Min; Jing, Tian; Zhuang, Yu; Kou, Junping; Qiu, Zhixia; Wang, Jubo; Li, Zhiyu; Bian, Jinlei published an article in European Journal of Medicinal Chemistry. The title of the article was 《Discovery of novel glutaminase 1 allosteric inhibitor with 4-piperidinamine linker and aromatic heterocycles》.Related Products of 87120-72-7 The author mentioned the following in the article:

Glutaminase 1 (GLS1) is overexpressed in multiple types of malignant tumors and is viewed as a promising target in cancer therapy. Thus, the discovery for small-mol. GLS1 inhibitors is urgent. Based on the authors’ previous study of compound I, a potent GLS1 allosteric inhibitor yet with a limited metabolic stability, a structure-based optimization was carried out, with a series of novel GLS1 allosteric inhibitors rationally designed, synthesized and biol. evaluated. Such endeavor has culminated in the identification of compound II, a promising GLS1 allosteric inhibitor with a 4-piperidinamine linker and aromatic heterocycles. Compound II displayed robust GLS1 binding affinity, superior liver microsome metabolic stability, and moderate anti-tumor activity (TGI: 47.5%) in HCT116 xenograft model with no considerable toxicity in vivo. The mechanism underlying the anti-proliferative effect of compound II on HCT116 cells was studied, revealing that the compound blocked the glutamine metabolism, induced the production of ROS, and triggered apoptosis. These findings merit further investigation of compound II as a targeted cancer therapeutic. The experimental part of the paper was very detailed, including the reaction process of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Related Products of 87120-72-7)

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.Related Products of 87120-72-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

HPLC of Formula: 1445-73-4In 2020 ,《Propargylated monocarbonyl curcumin analogues: synthesis, bioevaluation and molecular docking study》 appeared in Medicinal Chemistry Research. The author of the article were Nagargoje, Amol A.; Akolkar, Satish V.; Subhedar, Dnyaneshwar D.; Shaikh, Mubarak H.; Sangshetti, Jaiprakash N.; Khedkar, Vijay M.; Shingate, Bapurao B.. The article conveys some information:

Abstract: In the current exptl. study, we have synthesized new monocarbonyl curcumin analogs bearing propargyl ether moiety in their structure and evaluated for in vitro antifungal and radical scavenging activity. The antifungal activity was carried out against five human pathogenic fungal strains such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger and Cryptococcus neoformans. Most of the curcumin analogs displayed excellent to moderate fungicidal activity when compared with standard drug Miconazole. Also, synthesized analogs exhibited potential radical scavenging activity as compared with standard antioxidant Butylated hydroxyl toluene (BHT). Based on biol. data, structure-activity relationship (SAR) were also discussed. Furthermore, in silico computational study was carried out to know binding interactions of synthesized analogs in the active sites of enzyme sterol 14α-demethylase (CYP51). [graphic not available: see fulltext] In addition to this study using 1-Methyl-4-piperidone, there are many other studies that have used 1-Methyl-4-piperidone(cas: 1445-73-4HPLC of Formula: 1445-73-4) was used in this study.

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.HPLC of Formula: 1445-73-4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Electric Literature of C6H11NOIn 2021 ,《In Situ-Doped Superacid in the Covalent Triazine Framework Membrane for Anhydrous Proton Conduction in a Wide Temperature Range from Subzero to Elevated Temperature》 was published in ACS Applied Materials & Interfaces. The article was written by Huang, Wenbo; Li, Bin; Wu, Yue; Zhang, Ying; Zhang, Wenxiang; Chen, Shuhui; Fu, Yu; Yan, Tong; Ma, Heping. The article contains the following contents:

Synthesis of solid-state proton-conducting membranes with low activation energy and high proton conductivity under anhydrous conditions is a great challenge. Here, we show a simple and convenient way to prepare covalent triazine framework membranes (CTF-Mx) with acid in situ doping for anhydrous proton conduction in a wide temperature range from subzero to elevated temperature (160 °C). The low proton dissociation energy and continuous hydrogen bond network in CTF-Mx make the membrane achieve high proton conductivity from 1.21×10-3 S cm-1 (-40 °C) to 2.08×10-2 S cm-1 (160 °C) under anhydrous conditions. Mol. dynamics and proton relaxation time analyses reveal proton hopping at low activation energies with greatly enhanced mobility in the CTF membranes. After reading the article, we found that the author used 1-Methyl-4-piperidone(cas: 1445-73-4Electric Literature of C6H11NO)

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.Electric Literature of C6H11NO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Correlation Study Between Biochemical and Molecular Pathways of Trichoderma harzianum Recombinant Strains on Plant Growth and Health》 was written by Eslahi, Negin; Kowsari, Mojegan; Zamani, Mohammad Reza; Motallebi, Mostafa. Application In Synthesis of Triacetonamine And the article was included in Journal of Plant Growth Regulation on April 30 ,2022. The article conveys some information:

The genus of Trichoderma are mostly found in soil. Trichoderma species are known as probiotic with biocontrol and biofertilizer activity. They are producers of secondary metabolites like volatile organic compounds (VOCs) with antifungal, antibacterial, and growth promoter properties. Trichoderma VOCs can induce resistance to plant pathogens leading to improved plant growth and health. In this study, we compared the performance of Trichoderma harzianum recombinant strains (T13 and T15), containing chimeric chit42 with Chitin Binding Domain (ChBD) and wild-type (Tw) strain on plant growth promotion. To achieve this goal, the ability of strains in plant growth-promoting (production of IAA and siderophore) and fungal gene expression involved in biocontrol and biofertilizer activity, as well as, VOCs from T. harzianum strains (wild-type and recombinants) by headspace gas chromatog.-mass spectrometry (GC-SPME) have been investigated. In addition, bean seeds were exposed to the T. harzianum strains in a shared atm. In addition to growth indexes (root fresh and dry weight, root length, and lateral root number), expression of root growth-related genes was measured by qTR-PCR. The results showed that recombinant strains had increased ability to produce IAA and siderophore. In addition, T. harzianum genes expression anal. demonstrated an upregulation in biocontrol and biofertilizer-associated genes in T13 and T15 strains. VOCs profile of strains revealed a total of 11, 57, and 29 metabolites from the Tw, T15, and T13, resp. Most of the VOCs produced from T13 and T15 had growth enhancement and biocontrol activity, resp., on the plant. The diversity of VOCs from T. harzianum recombinant strains (T13 and T15) involved in growth-promoting and biocontrol activity, was higher than the Tw strain. These compounds might work synergistically to promote growth, and enhance biocontrol and antifungal activity, and thus, recombinant strains with higher diversity of VOCs might be more effective than Tw. Plant phenotypic characterization and root genes expression showed that the recombinant strains, T13 particularly, were effective in growth-promoting compared to the Tw strain. In this study, we observed a pos. correlation among the production of secondary metabolite and mol. pathways of recombinant strains on plant growth activity. This finding can create a link between basic and applied studies in agriculture. The experimental process involved the reaction of Triacetonamine(cas: 826-36-8Application In Synthesis of Triacetonamine)

Triacetonamine(cas: 826-36-8) 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.Application In Synthesis of Triacetonamine

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Discovery of novel xanthine compounds targeting DPP-IV and GPR119 as anti-diabetic agents》 was written by Li, Gang; Huan, Yi; Yuan, Baokun; Wang, Jin; Jiang, Qian; Lin, Ziyun; Shen, Zhufang; Huang, Haihong. Computed Properties of C7H15NOThis research focused onxanthine derivative preparation GPR119 DPPIV targeting diabetes; DPP-IV; Dual ligands; GPR119; Merged pharmacophores; Xanthine derivatives. The article conveys some information:

A series of xanthine derivatives as potent dual ligands targeting DPP-IV and GPR119 was discovered through an approach of the merged pharmacophores of GPR119 agonists and DPP-IV inhibitor linagliptin. Systematic optimization of general structure 5 led to the identification of compound 20i with selective DPP-IV inhibition, good GPR119 agonism activity and favorable metabolic stability. Docking study was performed to elucidate the potent DPP-IV inhibition of 20i. Compound 20i may serve as a tool compound for further design of anti-diabetic drugs targeting both DPP-IV and GPR119. The experimental part of the paper was very detailed, including the reaction process of 2-(Piperidin-4-yl)ethanol(cas: 622-26-4Computed Properties of C7H15NO)

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 FAKComputed Properties of C7H15NO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem