Day: February 22, 2023

Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA₂) was written by Woolford, Alison J.-A.;Day, Philip J.;Beneton, Veronique;Berdini, Valerio;Coyle, Joseph E.;Dudit, Yann;Grondin, Pascal;Huet, Pascal;Lee, Lydia Y. W.;Manas, Eric S.;McMenamin, Rachel L.;Murray, Christopher W.;Page, Lee W.;Patel, Vipulkumar K.;Potvain, Florent;Rich, Sharna J.;Sang, Yingxia;Somers, Don O.;Trottet, Lionel;Wan, Zehong;Zhang, Xiaomin. And the article was included in Journal of Medicinal Chemistry in 2016.Computed Properties of C14H17NO3 This article mentions the following:

Lp-PLA₂ has been explored as a target for a number of inflammation associated diseases, including cardiovascular disease and dementia. This article describes the discovery of a new fragment derived chemotype that interacts with the active site of Lp-PLA₂. The starting fragment hit was discovered through an x-ray fragment screen and showed no activity in the bioassay (IC₅₀ > 1 mM). The fragment hit was optimized using a variety of structure-based drug design techniques, including virtual screening, fragment merging, and improvement of shape complementarity. A novel series of Lp-PLA₂ inhibitors was generated with low lipophilicity and a promising pharmacokinetic profile. In the experiment, the researchers used many compounds, for example, Benzyl 4-formylpiperidine-1-carboxylate (cas: 138163-08-3Computed Properties of C14H17NO3).

Benzyl 4-formylpiperidine-1-carboxylate (cas: 138163-08-3) 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. 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.Computed Properties of C14H17NO3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Cellulose dissolution in aqueous NaOH-ZnO: effect of pulp pretreatment at macro and molecular levels was written by Vaisanen, Saija;Kosonen, Harri;Ristolainen, Matti;Vuorinen, Tapani. And the article was included in Cellulose (Dordrecht, Netherlands) in 2021.Synthetic Route of C11H21N2O2 This article mentions the following:

This paper discusses the effect of hydrolytic pretreatments on pulp dissolution in the aqueous NaOH-ZnO solvent system. Eight samples were studied. They consisted of a never-dried softwood kraft pulp that was hydrolyzed under seven different conditions as well as the pulp without hydrolysis as a reference The dissolution of the pulps was evaluated both at the macro level as well as at the mol. level based on their reactivity with 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxo-piperidium (4-AcNH-TEMPO+). The fiber properties (i.e. the extent of fibrillation, amount of fines and fiber width, coarseness, and length) as well as the chem. composition (hemicellulose and cellulose contents) and the viscosity of the pulps was investigated. The results show that hydrolysis at medium consistency (10%) was successful in increasing the solubility of cellulose. Hydrolysis at high consistency (50%), on the other hand, increased the solubility only to some extent. With extended treatment time the fibers formed aggregates and their dissolution became poor. This phenomenon could be overcome by mech. refining the fibers after the hydrolysis. Moreover, comparison of the viscosity of the pulp over the degree of oxidation revealed that the viscosity needed to decrease below ca. 400 mL/g in order for the outer layers of the fibers to dissolve. Finally, when pulps with similar viscosities where compared against each other, the ones with the higher glucomannan contents formed gels over time. In the experiment, the researchers used many compounds, for example, 4-Acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (cas: 14691-89-5Synthetic Route of C11H21N2O2).

4-Acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (cas: 14691-89-5) 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 bearing a masked aldehyde function in the 蔚-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Synthetic Route of C11H21N2O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Three-Component Coupling of Aldehydes, 2-Aminopyridines, and Diazo Esters via Rhodium(III)-Catalyzed Imidoyl C-H Activation: Synthesis of Pyrido[1,2-a]pyrimidin-4-ones was written by Hoang, Gia L.;Zoll, Adam J.;Ellman, Jonathan A.. And the article was included in Organic Letters in 2019.Formula: C14H17NO3 This article mentions the following:

Imines formed in situ from 2-aminopyridines and aldehydes undergo Rh(III)-catalyzed imidoyl C-H activation and coupling with diazo esters to give pyrido[1,2-a]pyrimidin-4-ones. Aromatic and enolizable aliphatic aldehydes were both effective substrates, and a broad range of functional groups were incorporated at different sites on the heterocyclic products. In addition, methoxy and dimethylamino functionalities could be directly installed on the pyrimidine ring by employing tri-Me orthoformate or N,N-dimethylformamide di-Me acetal in place of the aldehyde, resp. In the experiment, the researchers used many compounds, for example, Benzyl 4-formylpiperidine-1-carboxylate (cas: 138163-08-3Formula: C14H17NO3).

Benzyl 4-formylpiperidine-1-carboxylate (cas: 138163-08-3) 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.Formula: C14H17NO3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase was written by Eldrup, Anne B.;Soleymanzadeh, Fariba;Farrow, Neil A.;Kukulka, Alison;De Lombaert, Stephane. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2010.Synthetic Route of C11H14FNO This article mentions the following:

Inhibition of sEH is hypothesized to lead to an increase in epoxyeicosatrienoic acids resulting in the potentiation of their anti-inflammatory and vasodilatory effects. In an effort to explore sEH inhibition as an avenue for the development of vasodilatory and cardio- or renal-protective agents, a lead identified through high-throughput screening was optimized, guided by the determination of a solid state co-structure with sEH. Replacement of potential toxicophores was followed by optimization of cell-based potency and ADME properties to provide a new class of functionally potent sEH inhibitors with attractive in vitro metabolic profiles and high and sustained plasma exposures after oral administration in the rat. In the experiment, the researchers used many compounds, for example, 4-(4-Fluorophenoxy)piperidine (cas: 3413-28-3Synthetic Route of C11H14FNO).

4-(4-Fluorophenoxy)piperidine (cas: 3413-28-3) 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. 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.Synthetic Route of C11H14FNO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Quinazoline-based hydroxamic acid derivatives as dual histone methylation and deacetylation inhibitors for potential anticancer agents was written by Zheng, Haoting;Dai, Qiuzi;Yuan, Zigao;Fan, Tingting;Zhang, Cunlong;Liu, Zijian;Chu, Bizhu;Sun, Qinsheng;Chen, Yan;Jiang, Yuyang. And the article was included in Bioorganic & Medicinal Chemistry in 2022.Synthetic Route of C6H14N2 This article mentions the following:

In the present work, a series of quinazoline-based hydroxamic acid derivatives I (n = 5, 6; R = Me, i-Pr, Bn), II and III as dual GLP and HDAC inhibitors were designed and synthesized. These hybrid compounds I, II and III showed potent enzymic inhibitory activities against GLP and HDAC1/6 with IC₅₀ values in the nanomolar range of less than 190 nM. Furthermore, most of the compounds displayed significant broad spectrum cytotoxic activities apart from I (n = 5; R = i-Pr) and III against all the tested cancer cells with IC₅₀ values less than 50渭M. Compounds I (n = 5; R = Me, n = 5; R = Bn) and II (R = Bn) (IV) showed more potent cytotoxic activities than I (n = 6; R = Me, n = 6; R = i-Pr) and II (R = i-Pr) in those cancer cells. Especially, compound IV showed potent inhibitory potency activity against both GLP and HDAC1/6 with IC₅₀ values of 1.3, 89, 13 nM. Besides, IV exhibited the most potent antiproliferative activity against all the tested cancer cells. Further evaluations indicated that IV could inhibit the methylation and deacetylation of H3K9 on protein level. Moreover, IV could induce cancer cell apoptosis, G0/G1 cell cycle arrest, and partly block migration and invasion. All these thorough evaluations warranted IV as a promising lead compound worth further optimization and development for cancer therapy. In the experiment, the researchers used many compounds, for example, 4-Amino-1-methylpiperidine (cas: 41838-46-4Synthetic Route of C6H14N2).

4-Amino-1-methylpiperidine (cas: 41838-46-4) 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.Synthetic Route of C6H14N2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In situ approach for testing the enantiopurity of chiral amines and amino alcohols by ¹H NMR was written by Mishra, Sandeep Kumar;Chaudhari, Sachin R.;Suryaprakash, N.. And the article was included in Organic & Biomolecular Chemistry in 2014.Formula: C6H13N This article mentions the following:

An in situ approach involving a simple mix and shake method for testing the enantiopurity of primary, secondary and tertiary chiral amines and their derivatives, chiral amino alcs., by ¹H-NMR spectroscopy is developed. The protocol involves the in situ formation of chiral ammonium borate salt from a mixture of C₂ sym. chiral BINOL, trialkoxyborane and chiral amines. The proposed concept was demonstrated convincingly on a large number of chiral and pro-chiral amines and amino alcs., and also aids the precise measurement of enantiomeric excess. The protocol can be completed in a couple of minutes directly in the NMR sample tube, without the need for any phys. separation In the experiment, the researchers used many compounds, for example, (R)-2-Methylpiperidine (cas: 1722-95-8Formula: C6H13N).

(R)-2-Methylpiperidine (cas: 1722-95-8) 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.Formula: C6H13N

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

A Comparative Molecular Field Analysis Study of N-Benzylpiperidines as Acetylcholinesterase Inhibitors was written by Tong, Weida;Collantes, Elizabeth R.;Chen, Yu;Welsh, William J.. And the article was included in Journal of Medicinal Chemistry in 1996.Safety of 5,6-Dimethoxy-2-(piperidin-4-ylmethyl)-2,3-dihydro-1H-inden-1-one This article mentions the following:

A series of 1-benzyl-4-[2-(N-benzoylamino)ethyl]piperidine derivatives and of N-benzylpiperidine benzisoxazoles have been investigated using the comparative mol. field anal. (CoMFA) approach. These compounds have been found to inhibit the metabolic breakdown of the neurotransmitter acetylcholine (ACh) by the enzyme acetylcholinesterase (AChE) and hence alleviate memory deficits in patients with Alzheimer’s disease by potentiating cholinergic transmission. Development of the CoMFA model considered two sep. alignments: (i) alignment I which emphasized the electrostatic fitting of the subject compounds and (ii) alignment II which emphasized their steric fitting. In addition, the inhibitor compounds were considered both as neutral species and as N-piperidine-protonated species. The resulting 3D-QSAR indicates a strong correlation between the inhibitory activity of these N-benzylpiperidines and the steric and electronic factors which modulate their biochem. activity. A CoMFA model with considerable predictive ability was obtained. In the experiment, the researchers used many compounds, for example, 5,6-Dimethoxy-2-(piperidin-4-ylmethyl)-2,3-dihydro-1H-inden-1-one (cas: 120014-30-4Safety of 5,6-Dimethoxy-2-(piperidin-4-ylmethyl)-2,3-dihydro-1H-inden-1-one).

5,6-Dimethoxy-2-(piperidin-4-ylmethyl)-2,3-dihydro-1H-inden-1-one (cas: 120014-30-4) 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. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Safety of 5,6-Dimethoxy-2-(piperidin-4-ylmethyl)-2,3-dihydro-1H-inden-1-one

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Absence, loss-of-function, or inhibition of Escherichia coli AcrB does not increase expression of other efflux pump genes supporting the discovery of AcrB inhibitors as antibiotic adjuvants was written by Ciusa, Maria Laura;Marshall, Robert L.;Ricci, Vito;Stone, Jack W.;Piddock, Laura J. V.. And the article was included in Journal of Antimicrobial Chemotherapy in 2022.HPLC of Formula: 50-52-2 This article mentions the following:

To determine whether expression of efflux pumps and antibiotic susceptibility are altered in Escherichia coli in response to efflux inhibition. The promoter regions of nine efflux pump genes (acrAB, acrD, acrEF, emrAB, macAB, cusCFBA, mdtK, mdtABC, mdfA) were fused to gfp in pMW82 and fluorescence from each reporter construct was used as a measure of the transcriptional response to conditions in which AcrB was inhibited, absent or made non-functional. Expression was also determined by RT-qPCR. Drug susceptibility of efflux pump mutants with missense mutations known or predicted to cause loss of function of the encoded efflux pump was investigated. Data from the GFP reporter constructs revealed that no increased expression of the tested efflux pump genes was observed when AcrB was absent, made non-functional, or inhibited by an efflux pump inhibitor/competitive substrate, such as PA尾N or chlorpromazine. This was confirmed by RT-qPCR for PA尾N and chlorpromazine; however, a small but significant increase in macB gene expression was seen when acrB is deleted. Efflux inhibitors only synergized with antibiotics in the presence of a functional AcrB. When AcrB was absent or non-functional, there was no impact on MICs when other efflux pumps were also made non-functional. Absence, loss-of-function, or inhibition of E. coli AcrB did not significantly increase expression of other efflux pump genes, which suggests there is no compensatory mechanism to overcome efflux inhibition and supports the discovery of inhibitors of AcrB as antibiotic adjuvants. In the experiment, the researchers used many compounds, for example, 10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine (cas: 50-52-2HPLC of Formula: 50-52-2).

10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine (cas: 50-52-2) 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.HPLC of Formula: 50-52-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Gram-Scale Synthesis of 1,8-Naphthyridines in Water: The Friedlander Reaction Revisited was written by Choudhury, Shubhranshu Shekhar;Jena, Subhrakant;Sahoo, Dipak Kumar;Shekh, Shamasoddin;Kar, Rajiv K.;Dhakad, Ambuj;Gowd, Konkallu Hanumae;Biswal, Himansu S.. And the article was included in ACS Omega in 2021.Reference of 3612-18-8 This article mentions the following:

Here, gram-scale synthesis of 1,8-naphthyridines I [R¹ = H, Me, Ph, etc.; R² = H, CO₂Me, Ph, etc.; R¹R² = (CH₂)₃, (CH₂)₄, (CH₂)₅, etc.] in water using an inexpensive and biocompatible ionic liquid (IL) as a catalyst was introduced. This was the first-ever report on the synthesis of naphthyridines I in water. This was a one-step reaction, and the product separation was relatively easy. The choline hydroxide (ChOH) was used as a metal-free, nontoxic and water-soluble catalyst. In comparison to other catalysts reported in the literature, ChOH had the advantage of forming an addnl. hydrogen bond with the reactants, which was the vital step for the reaction to happen in water. D. functional theory (DFT) and noncovalent interaction (NCI) plot index anal. provided the plausible reaction mechanism for the catalytic cycle and confirmed that hydrogen bonds with the IL catalyst were pivotal to facilitate the reaction. Mol. docking and mol. dynamics (MD) simulations were also performed to demonstrate the potentialities of the newly synthesized products as drugs. Through MD simulations, it was established that the tetrahydropyrido derivative of naphthyridine I [R¹R² = CH₂CH₂N(Et)CH₂] bound to the active sites of the ts3 human serotonin transporter (hSERT) (PDB ID: 6AWO) without perturbing the secondary structure, suggesting that compound I [R¹R² = CH₂CH₂N(Et)CH₂] could be a potential preclin. drug candidate for hSERT inhibition and depression treatment. In the experiment, the researchers used many compounds, for example, 1-Ethylpiperidin-4-one (cas: 3612-18-8Reference of 3612-18-8).

1-Ethylpiperidin-4-one (cas: 3612-18-8) 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. 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.Reference of 3612-18-8

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

The efficacy of curcumin-piperine co-supplementation on clinical symptoms, duration, severity, and inflammatory factors in COVID-19 outpatients: a randomized double-blind, placebo-controlled trial was written by Askari, Gholamreza;Sahebkar, Amirhossein;Soleimani, Davood;Mahdavi, Atena;Rafiee, Sahar;Majeed, Muhammed;Khorvash, Farzin;Iraj, Bijan;Elyasi, Mahshid;Rouhani, Mohammad Hossein;Bagherniya, Mohammad. And the article was included in Trials in 2022.Recommanded Product: 94-62-2 This article mentions the following:

COVID-19 pandemic has made the disease a major global problem by creating a significant burden on health, economic, and social status. To date, there are no effective and approved medications for this disease. Curcumin as an anti-inflammatory agent can have a pos. effect on the control of COVID-19 complications. This study aimed to assess the efficacy of curcumin-piperine supplementation on clin. symptoms, duration, severity, and inflammatory factors in patients with COVID-19. Forty-six outpatients with COVID-19 disease were randomly allocated to receive two capsules of curcumin-piperine; each capsule contained 500 mg curcumin plus 5 mg piperine or placebo for 14 days. Mean changes in complete blood count, liver enzymes, blood glucose levels, lipid parameters, kidney function, and c-reactive protein (CRP) were not significantly different between the two groups. There was a significant improvement in health status, including dry cough, sputum cough, ague, sore throat, weakness, muscular pain, headache, and dyspnea at week 2 in both curcumin-piperine and placebo groups (P value < 0.05); however, the improvement in weakness was more in the curcumin-piperine group than with placebo group (P value 025). The present study results showed that curcumin-piperine co-supplementation in outpatients with COVID-19 could significantly reduce weakness. However, in this study, curcumin-piperine co-supplementation could not significantly affect the other indexes, including biochem. and clin. indexes. In the experiment, the researchers used many compounds, for example, (2E,4E)-5-(Benzo[d][1,3]dioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one (cas: 94-62-2Recommanded Product: 94-62-2).

(2E,4E)-5-(Benzo[d][1,3]dioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one (cas: 94-62-2) 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. 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.Recommanded Product: 94-62-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem