Month: November 2022

Macrocyclic FKBP51 Ligands Define a Transient Binding Mode with Enhanced Selectivity was written by Voll, Andreas M.;Meyners, Christian;Taubert, Martha C.;Bajaj, Thomas;Heymann, Tim;Merz, Stephanie;Charalampidou, Anna;Kolos, Juergen;Purder, Patrick L.;Geiger, Thomas M.;Wessig, Pablo;Gassen, Nils C.;Bracher, Andreas;Hausch, Felix. And the article was included in Angewandte Chemie, International Edition in 2021.Application In Synthesis of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

Subtype selectivity represents a challenge in many drug discovery campaigns. A typical example is the FK506 binding protein 51 (FKBP51), which has emerged as an attractive drug target. The most advanced FKBP51 ligands of the SAFit class are highly selective vs. FKBP52 but poorly discriminate against the homologs and off-targets FKBP12 and FKBP12.6. During a macrocyclization pilot study, we observed that many of these macrocyclic analogs have unanticipated and unprecedented preference for FKBP51 over FKBP12 and FKBP12.6. Structural studies revealed that these macrocycles bind with a new binding mode featuring a transient conformation, which is disfavored for the small FKBPs. Using a conformation-sensitive assay we show that this binding mode occurs in solution and is characteristic for this new class of compounds The discovered macrocycles are non-immunosuppressive, engage FKBP51 in cells, and block the cellular effect of FKBP51 on IKK伪. Our findings provide a new chem. scaffold for improved FKBP51 ligands and the structural basis for enhanced selectivity. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Application In Synthesis of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Application In Synthesis of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Identification of the Key Residue of Calcitonin Gene Related Peptide (CGRP) 27-37 to Obtain Antagonists with Picomolar Affinity at the CGRP Receptor was written by Lang, Manja;De Pol, Silvia;Baldauf, Carsten;Hofmann, Hans-Joerg;Reiser, Oliver;Beck-Sickinger, Annette G.. And the article was included in Journal of Medicinal Chemistry in 2006.Application In Synthesis of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

Calcitonin gene related peptide (CGRP) plays an important role in the CNS and in the cardiovascular system. To identify high-affinity antagonists in competitive binding studies, the authors identified a novel radioactive tracer, [³H-propionyl-K²⁴]-h伪CGRP 8-37, which was labeled in solution by a recently developed strategy using photolabile protecting groups at reactive side chains. This tracer was shown to be as potent as com. available ¹²⁵I-tracers for the determination of agonists and to have increased sensitivity for antagonists. The authors applied it to investigate the predicted turn structures centered at Pro²⁹ and Pro³⁴. The substitution at positions 29 and 34 by turn-inducing amino acid mimetica showed that these turns are highly diverse. At position 29, a hydrophobic residue is preferred that constricts the secondary structure, whereas position 34 is required to stabilize the conformation of the backbone. All high-affinity analogs showed antagonistic properties with potency similar to CGRP 8-37. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Application In Synthesis of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Several piperidine alkaloids isolated from natural herbs, were found to exhibit antiproliferation and antimetastatic effects on various types of cancers both in vitro and in vivo for example Piperine, Evodiamine, Matrine, Berberine and Tetrandine.Application In Synthesis of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Identification of the Key Residue of Calcitonin Gene Related Peptide (CGRP) 27-37 to Obtain Antagonists with Picomolar Affinity at the CGRP Receptor was written by Lang, Manja;De Pol, Silvia;Baldauf, Carsten;Hofmann, Hans-Joerg;Reiser, Oliver;Beck-Sickinger, Annette G.. And the article was included in Journal of Medicinal Chemistry in 2006.Computed Properties of C21H21NO4 The following contents are mentioned in the article:

Calcitonin gene related peptide (CGRP) plays an important role in the CNS and in the cardiovascular system. To identify high-affinity antagonists in competitive binding studies, the authors identified a novel radioactive tracer, [³H-propionyl-K²⁴]-h伪CGRP 8-37, which was labeled in solution by a recently developed strategy using photolabile protecting groups at reactive side chains. This tracer was shown to be as potent as com. available ¹²⁵I-tracers for the determination of agonists and to have increased sensitivity for antagonists. The authors applied it to investigate the predicted turn structures centered at Pro²⁹ and Pro³⁴. The substitution at positions 29 and 34 by turn-inducing amino acid mimetica showed that these turns are highly diverse. At position 29, a hydrophobic residue is preferred that constricts the secondary structure, whereas position 34 is required to stabilize the conformation of the backbone. All high-affinity analogs showed antagonistic properties with potency similar to CGRP 8-37. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Computed Properties of C21H21NO4).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Computed Properties of C21H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Modified Peptide Inhibitors of the Keap1-Nrf2 Protein-Protein Interaction Incorporating Unnatural Amino Acids was written by Georgakopoulos, Nikolaos D.;Talapatra, Sandeep K.;Gatliff, Jemma;Kozielski, Frank;Wells, Geoff. And the article was included in ChemBioChem in 2018.Formula: C21H21NO4 The following contents are mentioned in the article:

Noncovalent inhibitors of the Keap1-Nrf2 protein-protein interaction (PPI) have therapeutic potential in a range of disease states including neurodegenerative diseases (Parkinson鈥瞫 and Alzheimer鈥瞫 diseases), chronic obstructive pulmonary disease and various inflammatory conditions. By stalling Keap1-mediated ubiquitination of Nrf2, such compounds can enhance Nrf2 transcriptional activity and activate the expression of a range of genes with antioxidant response elements in their promoter regions. Keap1 inhibitors based on peptide and small-mol. templates have been identified. In this paper we develop the structure-activity relationships of the peptide series and identify a group of ligands incorporating unnatural amino acids that demonstrate improved binding affinity in fluorescence polarisation, differential scanning fluorimetry and isothermal titration calorimetry assays. These modified peptides have the potential for further development into peptidomimetic chem. probes to explore the role of Nrf2 in disease and as potential lead structures for drug development. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Formula: C21H21NO4).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. Piperidine derivatives bearing a masked aldehyde function in the 蔚-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Formula: C21H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Modified Peptide Inhibitors of the Keap1-Nrf2 Protein-Protein Interaction Incorporating Unnatural Amino Acids was written by Georgakopoulos, Nikolaos D.;Talapatra, Sandeep K.;Gatliff, Jemma;Kozielski, Frank;Wells, Geoff. And the article was included in ChemBioChem in 2018.Reference of 86069-86-5 The following contents are mentioned in the article:

Noncovalent inhibitors of the Keap1-Nrf2 protein-protein interaction (PPI) have therapeutic potential in a range of disease states including neurodegenerative diseases (Parkinson鈥瞫 and Alzheimer鈥瞫 diseases), chronic obstructive pulmonary disease and various inflammatory conditions. By stalling Keap1-mediated ubiquitination of Nrf2, such compounds can enhance Nrf2 transcriptional activity and activate the expression of a range of genes with antioxidant response elements in their promoter regions. Keap1 inhibitors based on peptide and small-mol. templates have been identified. In this paper we develop the structure-activity relationships of the peptide series and identify a group of ligands incorporating unnatural amino acids that demonstrate improved binding affinity in fluorescence polarisation, differential scanning fluorimetry and isothermal titration calorimetry assays. These modified peptides have the potential for further development into peptidomimetic chem. probes to explore the role of Nrf2 in disease and as potential lead structures for drug development. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Reference of 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Reference of 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Chemical Optimization of New Ligands of the Low-Density Lipoprotein Receptor as Potential Vectors for Central Nervous System Targeting was written by Malcor, Jean-Daniel;Payrot, Nadine;David, Marion;Faucon, Aude;Abouzid, Karima;Jacquot, Guillaume;Floquet, Nicolas;Debarbieux, Franck;Rougon, Genevieve;Martinez, Jean;Khrestchatisky, Michel;Vlieghe, Patrick;Lisowski, Vincent. And the article was included in Journal of Medicinal Chemistry in 2012.Formula: C21H21NO4 The following contents are mentioned in the article:

Drug delivery to the central nervous system is hindered by the presence of physiol. barriers such as the blood-brain barrier. To accomplish the task of nutrient transport, the brain endothelium is endowed with various transport systems, including receptor-mediated transcytosis (RMT). This system can be used to shuttle therapeutics into the central nervous system (CNS) in a noninvasive manner. Therefore, the low-d. lipoprotein receptor (LDLR) is a relevant target for delivering drugs. From an initial phage display biopanning, a series of peptide ligands for the LDLR was optimized leading to size reduction and improved receptor binding affinity with the identification of peptide 22 and its analogs. Further real-time biphoton microscopy experiments on living mice demonstrated the ability of peptide 22 to efficiently and quickly cross CNS physiol. barriers. This validation of peptide 22 led the authors to explore its binding on the extracellular LDLR domain from an NMR-oriented structural study and docking experiments This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Formula: C21H21NO4).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Formula: C21H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Chemical Optimization of New Ligands of the Low-Density Lipoprotein Receptor as Potential Vectors for Central Nervous System Targeting was written by Malcor, Jean-Daniel;Payrot, Nadine;David, Marion;Faucon, Aude;Abouzid, Karima;Jacquot, Guillaume;Floquet, Nicolas;Debarbieux, Franck;Rougon, Genevieve;Martinez, Jean;Khrestchatisky, Michel;Vlieghe, Patrick;Lisowski, Vincent. And the article was included in Journal of Medicinal Chemistry in 2012.Application In Synthesis of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

Drug delivery to the central nervous system is hindered by the presence of physiol. barriers such as the blood-brain barrier. To accomplish the task of nutrient transport, the brain endothelium is endowed with various transport systems, including receptor-mediated transcytosis (RMT). This system can be used to shuttle therapeutics into the central nervous system (CNS) in a noninvasive manner. Therefore, the low-d. lipoprotein receptor (LDLR) is a relevant target for delivering drugs. From an initial phage display biopanning, a series of peptide ligands for the LDLR was optimized leading to size reduction and improved receptor binding affinity with the identification of peptide 22 and its analogs. Further real-time biphoton microscopy experiments on living mice demonstrated the ability of peptide 22 to efficiently and quickly cross CNS physiol. barriers. This validation of peptide 22 led the authors to explore its binding on the extracellular LDLR domain from an NMR-oriented structural study and docking experiments This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Application In Synthesis of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. Piperidine derivatives are being utilized in different ways as anticancer, antiviral, antimalarial, antimicrobial, antifungal, antihypertension, analgesic, anti-inflammatory, anti-Alzheimer, antipsychotic and/or anticoagulant agents.Application In Synthesis of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Optimization of the 4-anilinoquin(az)oline scaffold as epidermal growth factor receptor (EGFR) inhibitors for chordoma utilizing a toxicology profiling assay platform was written by Bieberich, Andrew A.;Laitinen, Tuomo;Maffuid, Kaitlyn;Fatig, Raymond O. III;Torrice, Chad D.;Morris, David C.;Crona, Daniel J.;Asquith, Christopher R. M.. And the article was included in Scientific Reports in 2022.Reference of 83799-24-0 The following contents are mentioned in the article:

The 4-anilinoquin(az)oline is a well-known kinase inhibitor scaffold incorporated in clin. inhibitors including gefitinib, erlotinib, afatinib, and lapatinib, all of which have previously demonstrated activity against chordoma cell lines in vitro. We screened a focused array of compounds based on the 4-anilinoquin(az)oline scaffold against both U-CH1 and the epidermal growth factor receptor (EGFR) inhibitor resistant U-CH2. To prioritize the hit compounds for further development, we screened the compound set in a multiparameter cell health toxicity assay. The de-risked compounds were then screened against a wider panel of patient derived cell lines and demonstrated low micromolar efficacy in cells. We also investigated the properties that gave rise to the toxophore markers, including the structural and electronic features, while optimizing for EGFR in-cell target engagement. These de-risked leads present a potential new therapeutic avenue for treatment of chordomas and new chem. tools and probe compound 45 (UNC-CA359) to interrogate EGFR mediated disease phenotypes. This study involved multiple reactions and reactants, such as 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0Reference of 83799-24-0).

2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Reference of 83799-24-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Inhibitory Effects of Cranberry Juice and Its Components on Intestinal OATP1A2 and OATP2B1: Identification of Avicularin as a Novel Inhibitor was written by Morita, Tokio;Akiyoshi, Takeshi;Tsuchitani, Toshiaki;Kataoka, Hiroki;Araki, Naoya;Yajima, Kodai;Katayama, Kazuhiro;Imaoka, Ayuko;Ohtani, Hisakazu. And the article was included in Journal of Agricultural and Food Chemistry in 2022.Recommanded Product: 83799-24-0 The following contents are mentioned in the article:

Organic anion-transporting polypeptide (OATP) 1A2 and OATP2B1 mediate the intestinal absorption of drugs. This study aimed to identify fruit juices or fruit juice components that inhibit OATPs and assess the risk of associated food-drug interactions. Inhibitory potency was assessed by examining the uptake of [³H]estrone 3-sulfate and [³H]fexofenadine into HEK293 cells expressing OATP1A2 or OATP2B1. In vivo experiments were conducted using mice to evaluate the effects of cranberry juice on the pharmacokinetics of orally administered fexofenadine. Of eight examined fruit juices, cranberry juice inhibited the functions of both OATPs most potently. Avicularin, a component of cranberry juice, was identified as a novel OATP inhibitor. It exhibited IC₅₀ values of 9.0 and 37渭M for the inhibition of estrone 3-sulfate uptake mediated by OATP1A2 and OATP2B1, resp. A pharmacokinetic experiment revealed that fexofenadine exposure was significantly reduced (by 50%) by cranberry juice. Cranberry juice may cause drug interactions with OATP substrates. This study involved multiple reactions and reactants, such as 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0Recommanded Product: 83799-24-0).

2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising 伪-glucosidase inhibitors. The former are analogs of DNJ with an improved 伪-glucosidase inhibitory profile than that of DNJ. Boisson et al.Recommanded Product: 83799-24-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Eicosanoid regulation of debris-stimulated metastasis was written by Deng, Jianjun;Yang, Haixia;Haak, Victoria M.;Yang, Jun;Kipper, Franciele C.;Barksdale, Chantal;Hwang, Sung Hee;Gartung, Allison;Bielenberg, Diane R.;Subbian, Selvakumar;Ho, Koc-Kan;Ye, Xiang;Fan, Daidi;Sun, Yongkui;Hammock, Bruce D.;Panigrahy, Dipak. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2021.Synthetic Route of C16H20F3N3O3 The following contents are mentioned in the article:

Cancer therapy reduces tumor burden via tumor cell death (debris), which can accelerate tumor progression via the failure of inflammation resolution Thus, there is an urgent need to develop treatment modalities that stimulate the clearance or resolution of inflammation-associated debris. Here, we demonstrate that chemotherapy-generated debris stimulates metastasis by up-regulating soluble epoxide hydrolase (sEH) and the prostaglandin E2 receptor 4 (EP4). Therapy-induced tumor cell debris triggers a storm of proinflammatory and proangiogenic eicosanoid-driven cytokines. Thus, targeting a single eicosanoid or cytokine is unlikely to prevent chemotherapy-induced metastasis. Pharmacol. abrogation of both sEH and EP4 eicosanoid pathways prevents hepato-pancreatic tumor growth and liver metastasis by promoting macrophage phagocytosis of debris and counterregulating a protumorigenic eicosanoid and cytokine storm. Therefore, stimulating the clearance of tumor cell debris via combined sEH and EP4 inhibition is an approach to prevent debris-stimulated metastasis and tumor growth. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Synthetic Route of C16H20F3N3O3).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Piperidine derivatives bearing a masked aldehyde function in the 蔚-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Synthetic Route of C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem