Day: November 24, 2022

Identification of early intermediates of caspase activation using selective inhibitors and activity-based probes was written by Berger, Alicia B.;Witte, Martin D.;Denault, Jean-Bernard;Sadaghiani, Amir Masoud;Sexton, Kelly M. B.;Salvesen, Guy S.;Bogyo, Matthew. And the article was included in Molecular Cell in 2006.Synthetic Route of C21H21NO4 The following contents are mentioned in the article:

Caspases are cysteine proteases that are key effectors in apoptotic cell death. Currently, there is a lack of tools that can be used to monitor the regulation of specific caspases in the context of distinct apoptotic programs. We describe the development of highly selective inhibitors and active site probes and their applications to directly monitor executioner (caspase-3 and -7) and initiator (caspase-8 and -9) caspase activity. Specifically, these reagents were used to dissect the kinetics of caspase activation upon stimulation of apoptosis in cell-free extracts and intact cells. These studies identified a full-length caspase-7 intermediate that becomes catalytically activated early in the pathway and whose further processing is mediated by mature executioner caspases rather than initiator caspases. This form also shows distinct inhibitor sensitivity compared to processed caspase-7. Our data suggest that caspase-7 activation proceeds through a previously uncharacterized intermediate that is formed without cleavage of the intact zymogen. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Synthetic Route of C21H21NO4).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. 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.Synthetic Route of C21H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Identification of early intermediates of caspase activation using selective inhibitors and activity-based probes was written by Berger, Alicia B.;Witte, Martin D.;Denault, Jean-Bernard;Sadaghiani, Amir Masoud;Sexton, Kelly M. B.;Salvesen, Guy S.;Bogyo, Matthew. And the article was included in Molecular Cell in 2006.Name: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

Caspases are cysteine proteases that are key effectors in apoptotic cell death. Currently, there is a lack of tools that can be used to monitor the regulation of specific caspases in the context of distinct apoptotic programs. We describe the development of highly selective inhibitors and active site probes and their applications to directly monitor executioner (caspase-3 and -7) and initiator (caspase-8 and -9) caspase activity. Specifically, these reagents were used to dissect the kinetics of caspase activation upon stimulation of apoptosis in cell-free extracts and intact cells. These studies identified a full-length caspase-7 intermediate that becomes catalytically activated early in the pathway and whose further processing is mediated by mature executioner caspases rather than initiator caspases. This form also shows distinct inhibitor sensitivity compared to processed caspase-7. Our data suggest that caspase-7 activation proceeds through a previously uncharacterized intermediate that is formed without cleavage of the intact zymogen. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Name: (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 key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. 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.Name: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Brain-targeted chemical delivery of [Leu², Pip³]-TRH: synthesis and biological evaluation was written by Yoon, S.-H.;Wu, J.;Wu, W.-M.;Prokai, L.;Bodor, N.. And the article was included in Bioorganic & Medicinal Chemistry in 2000.COA of Formula: C21H21NO4 The following contents are mentioned in the article:

A chem. targeting system for [Leu², Pip³]-TRH (Gln,Leu,Pip) was synthesized in order to allow its specific delivery to the central nervous system (CNS). Sequential metabolism of the obtained ‘packaged’ chem. delivery system, (CDS), DHT-Pro-Pro-Gln-Leu-Pip-OCh, should yield a ‘locked-in’ precursor following the oxidative conversion of the dihydrotrigonellyl (DHT) to the trigonellyl (T⁺) moiety, followed by removal of the cholesteryl function and cleavage of the T⁺-Pro-Pro by prolyl endopeptidase. The antagonism of barbiturate-induced sleeping time was used to assess the activity of the CDS. The sleeping time after administration of vehicle and [Leu²]-TRH was 100.5卤6.3 min, and 78.2卤4.7 min, resp. The [Leu², Pip³]-TRH-CDS showed a significant decrease in sleeping time (58.2卤3.4 min) compared to the vehicle or [Leu²]-TRH. These results indicate successful brain delivery of the precursor construct, and an effective release of the active GlnLeuPip in the brain. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5COA of Formula: C21H21NO4).

(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. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.COA of Formula: C21H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Brain-targeted chemical delivery of [Leu², Pip³]-TRH: synthesis and biological evaluation was written by Yoon, S.-H.;Wu, J.;Wu, W.-M.;Prokai, L.;Bodor, N.. And the article was included in Bioorganic & Medicinal Chemistry in 2000.Synthetic Route of C21H21NO4 The following contents are mentioned in the article:

A chem. targeting system for [Leu², Pip³]-TRH (Gln,Leu,Pip) was synthesized in order to allow its specific delivery to the central nervous system (CNS). Sequential metabolism of the obtained ‘packaged’ chem. delivery system, (CDS), DHT-Pro-Pro-Gln-Leu-Pip-OCh, should yield a ‘locked-in’ precursor following the oxidative conversion of the dihydrotrigonellyl (DHT) to the trigonellyl (T⁺) moiety, followed by removal of the cholesteryl function and cleavage of the T⁺-Pro-Pro by prolyl endopeptidase. The antagonism of barbiturate-induced sleeping time was used to assess the activity of the CDS. The sleeping time after administration of vehicle and [Leu²]-TRH was 100.5卤6.3 min, and 78.2卤4.7 min, resp. The [Leu², Pip³]-TRH-CDS showed a significant decrease in sleeping time (58.2卤3.4 min) compared to the vehicle or [Leu²]-TRH. These results indicate successful brain delivery of the precursor construct, and an effective release of the active GlnLeuPip in the brain. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Synthetic Route of C21H21NO4).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N鈥揌 bond in an axial position, and the other in an equatorial position.Synthetic Route of C21H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

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.Electric Literature of C21H21NO4 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: 86069-86-5Electric Literature of C21H21NO4).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. 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.Electric Literature of C21H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

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