Day: November 24, 2022

C-Terminal Residue Optimization and Fragment Merging: Discovery of a Potent Peptide-Hybrid Inhibitor of Dengue Protease was written by Behnam, Mira A. M.;Nitsche, Christoph;Vechi, Sergio M.;Klein, Christian D.. And the article was included in ACS Medicinal Chemistry Letters in 2014.Related Products of 86069-86-5 The following contents are mentioned in the article:

Dengue virus protease is a promising target for the development of antiviral drugs. We describe here a two-step rational optimization that led to the discovery of the potent inhibitor 35 with nanomolar binding affinity at dengue protease serotype 2 (IC₅₀ = 0.6 渭M, K_i = 0.4 渭M). First, a large number of natural and non-natural amino acids were screened at the C-terminal position of the previously reported, canonical peptide sequence (Cap-Arg-Lys-Nle-NH₂). Compared to the reference compound 1 (Bz-Arg-Lys-Nle-NH₂, IC₅₀ = 13.3 渭M), a 4-fold higher inhibitory potential was observed with the incorporation of a C-terminal phenylglycine (compound 9, IC₅₀ = 3.3 渭M). Second, we applied fragment merging of 9 with the previously reported thiazolidinedione peptide hybrid 33 (IC₅₀ = 2.5 渭M). This approach led to the fusion of two inhibitor-fragments with micromolar affinity into a 20-fold more potent, competitive inhibitor of dengue protease. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Related Products 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 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 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.Related Products of 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

C-Terminal Residue Optimization and Fragment Merging: Discovery of a Potent Peptide-Hybrid Inhibitor of Dengue Protease was written by Behnam, Mira A. M.;Nitsche, Christoph;Vechi, Sergio M.;Klein, Christian D.. And the article was included in ACS Medicinal Chemistry Letters in 2014.Electric Literature of C21H21NO4 The following contents are mentioned in the article:

Dengue virus protease is a promising target for the development of antiviral drugs. We describe here a two-step rational optimization that led to the discovery of the potent inhibitor 35 with nanomolar binding affinity at dengue protease serotype 2 (IC₅₀ = 0.6 渭M, K_i = 0.4 渭M). First, a large number of natural and non-natural amino acids were screened at the C-terminal position of the previously reported, canonical peptide sequence (Cap-Arg-Lys-Nle-NH₂). Compared to the reference compound 1 (Bz-Arg-Lys-Nle-NH₂, IC₅₀ = 13.3 渭M), a 4-fold higher inhibitory potential was observed with the incorporation of a C-terminal phenylglycine (compound 9, IC₅₀ = 3.3 渭M). Second, we applied fragment merging of 9 with the previously reported thiazolidinedione peptide hybrid 33 (IC₅₀ = 2.5 渭M). This approach led to the fusion of two inhibitor-fragments with micromolar affinity into a 20-fold more potent, competitive inhibitor of dengue protease. 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. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. 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.Electric Literature of C21H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Neonicotine and isomeric pyridylpiperidines was written by Smith, C. R.. And the article was included in Journal of the American Chemical Society in 1931.Category: piperidines The following contents are mentioned in the article:

cf. C. A. 18, 2006. Details are given for the isolation of neonicotine (尾-pyridyl-伪-piperidine) (I) from the reaction product of C₅H₅N, Na and O; I b₇₇₅ 280-1掳 and yields a picrate, m. 213掳 (con.); this is probably not identical with nicotimine, isolated by Pictet and Rotschky (Ber. 34, 696(1901)) from the nicotine alkaloids. Reduction of I gives 伪,尾-dipiperidyl, b. 269-70掳. Reduction of 伪,尾-dipyridyl gives isoneonicotine (伪-pyridyl-尾-piperidine), b₇₆₀ 282掳, whose picrate m. 217-8掳 (corrected). 伪,伪-Pyridylpiperidyl, b₇₅₅ 265-6掳, whose picrate m. 187掳; the NO derivative is an oil. Isonicotine (纬,纬-pyridylpiperidine) b₇₆₀ 292掳; the picrate m. 215-8掳 (decomposition); the NO derivative m. 112掳. Nicotidine (尾,尾-pyridylpiperidine) b. 284-5掳; picrate m. about 206掳. 尾-Pyridyl-纬-piperidine yields a picrate, m. 240掳. The ease of reduction by Sn and HCl of the dipyridyls is in the order 纬,纬-, 尾,纬, 伪,伪- and 尾,尾, the first being the most easily reduced. This study involved multiple reactions and reactants, such as 3-(Piperidin-3-yl)pyridine (cas: 31251-28-2Category: piperidines).

3-(Piperidin-3-yl)pyridine (cas: 31251-28-2) 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. 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.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Combined Cardioprotective and Adipocyte Browning Effects Promoted by the Eutomer of Dual sEH/PPAR纬 Modulator was written by Hartmann, Markus;Bibli, Sofia-Iris;Tews, Daniel;Ni, Xiaomin;Kircher, Theresa;Kramer, Jan S.;Kilu, Whitney;Heering, Jan;Hernandez-Olmos, Victor;Weizel, Lilia;Scriba, Gerhard K. E.;Krait, Sulaiman;Knapp, Stefan;Chaikuad, Apirat;Merk, Daniel;Fleming, Ingrid;Fischer-Posovszky, Pamela;Proschak, Ewgenij. And the article was included in Journal of Medicinal Chemistry in 2021.Category: piperidines The following contents are mentioned in the article:

The metabolic syndrome (MetS) is a constellation of cardiovascular and metabolic symptoms involving insulin resistance, steatohepatitis, obesity, hypertension, and heart disease, and patients suffering from MetS often require polypharmaceutical treatment. PPAR纬 agonists are highly effective oral antidiabetics with great potential in MetS, which promote adipocyte browning and insulin sensitization. However, the application of PPAR纬 agonists in clinics is restricted by potential cardiovascular adverse events. We have previously demonstrated that the racemic dual sEH/PPAR纬 modulator RB394 (3) simultaneously improves all risk factors of MetS in vivo. In this study, we identify and characterize (R)-3 (I), the eutomer of 3. We provide structural rationale for mol. recognition of the eutomer. Furthermore, we could show that the dual sEH/PPAR纬 modulator is able to promote adipocyte browning and simultaneously exhibits cardioprotective activity which underlines its exciting potential in treatment of MetS. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Category: piperidines).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) 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 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.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Soluble epoxide hydrolase inhibitor, TPPU, increases regulatory T cells pathway in an arthritis model was written by Trindade-da-Silva, Carlos A.;Clemente-Napimoga, Juliana T.;Abdalla, Henrique B.;Rosa, Sergio Marcolino;Ueira-Vieira, Carlos;Morisseau, Christophe;Verri, Waldiceu A. Jr;Montalli, Victor Angelo Martins;Hammock, Bruce D.;Napimoga, Marcelo H.. And the article was included in FASEB Journal in 2020.Application of 1222780-33-7 The following contents are mentioned in the article:

Epoxyeicosatrienoic acids (EET) and related epoxy fatty acids (EpFA) are endogenous anti-inflammatory compounds, which are converted by the soluble epoxide hydrolase (sEH) to dihydroxylethersatrienoic acids (DHETs) with lessened biol. effects. Inhibition of sEH is used as a strategy to increase EET levels leading to lower inflammation. Rheumatoid arthritis is a chronic autoimmune disease that leads to destruction of joint tissues. This pathogenesis involves a complex interplay between the immune system, and environmental factors. Here, we investigate the effects of inhibiting sEH with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) on a collagen-induced arthritis model. The treatment with TPPU ameliorates hyperalgesia, edema, and decreases the expression of important pro-inflammatory cytokines of Th1 and Th17 profiles, while increasing Treg cells. Considering the challenges to control RA, this study provides robust data supporting that inhibition of the sEH is a promising target to treat arthritis. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Application of 1222780-33-7).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) 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. 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 of 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Divergent PGD₂ and leukotriene C₄ metabolite excretion following aspirin therapy: Ten patients with systemic mastocytosis was written by Butterfield, Joseph H.;Singh, Ravinder J.. And the article was included in Prostaglandins and Other Lipid Mediators in 2021.Electric Literature of C32H39NO4 The following contents are mentioned in the article:

Aspirin-exacerbated respiratory disease and some cases of chronic idiopathic urticaria are disorders in which increased baseline urinary excretion of leukotriene(LT)E4 further increases following aspirin administration. Increased urinary excretion of the metabolites of prostaglandin D2, 11尾-prostaglandin(PG)F2伪 and (2,3-dinor)-11尾-PGF2伪, have been documented in systemic mastocytosis (SM) and in mast cell activation syndrome (MCAS). Symptoms due to increased baseline and/or episodic release of PGD2 can be prevented with aspirin, an inhibitor of cyclooxygenase (COX)1 and COX2. Here by retrospective chart review we discovered 8 of 10 patients with SM in whom normalization of an elevated urinary (2,3-dinor)-11尾-PGF2伪 occurred with aspirin therapy also had a parallel increased excretion of LTE4 by an average of nearly 13-fold. How widespread this phenomenon occurs in SM is unknown; however, this occurrence needs to be considered when interpreting changes in these urinary mast cell mediator metabolites during aspirin therapy. 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: 83799-24-0Electric Literature of C32H39NO4).

2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. 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.Electric Literature of C32H39NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Evaluation of Synthetic FK506 Analogues as Ligands for the FK506-Binding Proteins 51 and 52 was written by Gopalakrishnan, Ranganath;Kozany, Christian;Gaali, Steffen;Kress, Christoph;Hoogeland, Bastiaan;Bracher, Andreas;Hausch, Felix. And the article was included in Journal of Medicinal Chemistry in 2012.COA of Formula: C21H21NO4 The following contents are mentioned in the article:

The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified 伪-ketoamide analog derived from FK506 and the first structure-activity relation anal. for FKBP51 and FKBP52 based on this compound In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was surprisingly tolerant to the stereochem. of the attached cyclohexyl substituents. The mol. basis for this tolerance was elucidated by x-ray cocrystallog. 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. 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.COA of Formula: C21H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Evaluation of Synthetic FK506 Analogues as Ligands for the FK506-Binding Proteins 51 and 52 was written by Gopalakrishnan, Ranganath;Kozany, Christian;Gaali, Steffen;Kress, Christoph;Hoogeland, Bastiaan;Bracher, Andreas;Hausch, Felix. And the article was included in Journal of Medicinal Chemistry in 2012.Safety of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified 伪-ketoamide analog derived from FK506 and the first structure-activity relation anal. for FKBP51 and FKBP52 based on this compound In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was surprisingly tolerant to the stereochem. of the attached cyclohexyl substituents. The mol. basis for this tolerance was elucidated by x-ray cocrystallog. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Safety 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. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Safety of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Soluble epoxide hydrolase inhibitor mediated analgesia lacks tolerance in rat models was written by Wagner, Karen M.;Atone, Jogen;Hammock, Bruce D.. And the article was included in Brain Research in 2020.Related Products of 1222780-33-7 The following contents are mentioned in the article:

Effectively treating chronic pain remains a therapeutic challenge in the clinic. Recent evidence has shown the inhibition of the soluble epoxide hydrolase (sEH) to be an effective strategy to limit chronic pain in preclin. models, horses and companion animals. Determining the safety of sEH inhibition in addition to this demonstrated efficacy is a critical step to the further development of sEH inhibitors (sEHI) as analgesics. Here we describe a comparison of the sEHI TPPU with other first in class analgesics for human chronic pain. We assess the development of tolerance to the analgesia mediated by TPPU with extended use. We also assess for CNS effects by measuring changes in motor control and functioning. The sEHI are multimodal analgesics that have demonstrated potent efficacy against chronic pain. They have previously been tested and show no reward potential using operant methods. The results of the current experiments show that they lack motor function effects and also lack the development of tolerance with extended dosing. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Related Products of 1222780-33-7).

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. 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.Related Products of 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Drug-Target Residence Time Affects in Vivo Target Occupancy through Multiple Pathways was written by Lee, Kin Sing Stephen;Yang, Jun;Niu, Jun;Ng, Connie J.;Wagner, Karen M.;Dong, Hua;Kodani, Sean D.;Wan, Debin;Morisseau, Christophe;Hammock, Bruce D.. And the article was included in ACS Central Science in 2019.Reference of 1222780-33-7 The following contents are mentioned in the article:

The drug discovery and development process is greatly hampered by difficulties in translating in vitro potency to in vivo efficacy. Recent studies suggest that the long-neglected drug-target residence time parameter complements classical drug affinity parameters (K_I, K_d, IC₅₀, or EC₅₀) and is a better predictor of in vivo efficacy. Compounds with a long drug-target residence time are often more efficacious in vivo. The impact, however, of the drug-target residence time on in vivo efficacy remains controversial due to difficulties in exptl. determining the in vivo target occupancy during drug treatment. To tackle this problem, an in vivo displacement assay was developed using soluble epoxide hydrolase as a biol. model. In this report, we exptl. demonstrated that drug-target residence time affects the duration of in vivo drug-target binding. In addition, the drug-target residence time plays an important role in modulating the rate of drug metabolism which also affects the efficacy of the drug. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Reference of 1222780-33-7).

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 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.Reference of 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem