Month: February 2023

Photocatalytic Oxyamination of Alkenes: Copper(II) Salts as Terminal Oxidants in Photoredox Catalysis was written by Reed, Nicholas L.;Herman, Madeline I.;Miltchev, Vladimir P.;Yoon, Tehshik P.. And the article was included in Organic Letters in 2018.Computed Properties of C12H15NO3S This article mentions the following:

A photocatalytic method for the oxyamination of alkenes using simple nucleophilic nitrogen atom sources in place of prefunctionalized electrophilic nitrogen atom donors is reported. Copper(II) is an inexpensive, practical, and uniquely effective terminal oxidant for this process. In contrast to oxygen, peroxides, and similar oxidants commonly utilized in non-photochem. oxidative methods, the use of copper(II) as a terminal oxidant in photoredox reactions avoids the formation of reactive heteroatom-centered radical intermediates that can be incompatible with electron-rich functional groups. As a demonstration of the generality of this concept, it has been shown that diamination and deoxygenation reactions can also be accomplished using similar photooxidative conditions. In the experiment, the researchers used many compounds, for example, 1-Tosylpiperidin-4-one (cas: 33439-27-9Computed Properties of C12H15NO3S).

1-Tosylpiperidin-4-one (cas: 33439-27-9) 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.Computed Properties of C12H15NO3S

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Chemical and pharmacological characterization of the TRPML calcium channel blockers ML-SI1 and ML-SI3 was written by Leser, Charlotte;Keller, Marco;Gerndt, Susanne;Urban, Nicole;Chen, Cheng-Chang;Schaefer, Michael;Grimm, Christian;Bracher, Franz. And the article was included in European Journal of Medicinal Chemistry in 2021.HPLC of Formula: 58333-75-8 This article mentions the following:

The members of the TRPML subfamily of non-selective cation channels (TRPML1-3) are involved in the regulation of important lysosomal and endosomal functions, and mutations in TRPML1 are associated with the neurodegenerative lysosomal storage disorder mucolipidosis type IV. In literature only two TRPML inhibitors, compound I : ML-SI1 and compound II : ML-SI3, have been published, albeit without clear information about stereochem. details. In this investigation authors developed total syntheses of both inhibitors. ML-SI1 was only obtained as a racemic mixture of inseparable diastereomers and showed activator-dependent inhibitory activity. The more promising tool is ML-SI3, hence ML-SI1 was not further investigated. For ML-SI3 authors confirmed by stereoselective synthesis that the trans-isomer is significantly more active than the cis-isomer. Separation of the enantiomers of trans-ML-SI3 further revealed that the (-)-isomer is a potent inhibitor of TRPML1 and TRPML2 (IC₅₀ values 1.6 and 2.3μM) and a weak inhibitor (IC50 12.5μM) of TRPML3, whereas the (+)-enantiomer is an inhibitor on TRPML1 (IC₅₀ 5.9μM), but an activator on TRPML 2 and 3. The anal. of 12 analogs and aromatic analog of ML-SI3 gave first insights into structure-activity relationships in this chemotype, and showed that a broad variety of modifications in both the N-arylpiperazine and the sulfonamide moiety is tolerated. In the experiment, the researchers used many compounds, for example, 4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8HPLC of Formula: 58333-75-8).

4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8) 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.HPLC of Formula: 58333-75-8

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

N-Acetyl-N-acyl-3-aminoquinazolinones as chemoselective acetylating agents was written by Atkinson, Robert S.;Barker, Emma;Sutcliffe, Michael J.. And the article was included in Chemical Communications (Cambridge) in 1996.Reference of 4045-22-1 This article mentions the following:

The title compounds, e.g. I, are highly selective acetylating agents for primary amines in the presence of secondary amines and, in particular, for the less sterically hindered of two different secondary amines. In the experiment, the researchers used many compounds, for example, 1-(4-Hydroxypiperidin-1-yl)ethanone (cas: 4045-22-1Reference of 4045-22-1).

1-(4-Hydroxypiperidin-1-yl)ethanone (cas: 4045-22-1) 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. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Reference of 4045-22-1

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Flow Photo-Nazarov Reactions of 2-Furyl Vinyl Ketones: Cyclizing a Class of Traditionally Unreactive Heteroaromatic Enones was written by Ashley, William L.;Timpy, Evan L.;Coombs, Thomas C.. And the article was included in Journal of Organic Chemistry in 2018.COA of Formula: C12H15NO3S This article mentions the following:

Nazarov reactions of 2-furyl vinyl ketones and related heteroaromatic enones, to produce furan-fused cyclopentanones using a flow photochem. approach, are described. Compounds possessing this connectivity between heterocycle and ketone (2-furyl, 2-benzofuryl, 2-thiophene-yl, and 2-benzothiophene-yl) have traditionally proven difficult or impossible to cyclize with typical Bronsted and Lewis acid mediated methods. Using mild flow photochem. conditions and acetic acid (AcOH) or hexafluoroisopropanol (HFIP) as solvent, these compounds were found to cyclize in 45-97% yields, with typical UV exposure times of 3.4-6.8 min. In all cases, 2-furyl and 2-thiophene-yl enones cyclized, whereas 2-benzofuryl and 2-benzothiophene-yl enones exhibited divergent properties with reactivity patterns tied to the identity of the vinyl group. This report discloses the first photo-Nazarov reactions of tetrahydropyridine-substituted 2-furyl ketones, providing a direct approach to the corresponding fused heterocyclic motifs built around a central cyclopentanone. These motifs constitute the core structures of biol. active natural products, including the marine alkaloid nakadomarin A. In the experiment, the researchers used many compounds, for example, 1-Tosylpiperidin-4-one (cas: 33439-27-9COA of Formula: C12H15NO3S).

1-Tosylpiperidin-4-one (cas: 33439-27-9) 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.COA of Formula: C12H15NO3S

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Functionally Biased D2R Antagonists: Targeting the β-Arrestin Pathway to Improve Antipsychotic Treatment was written by Weiwer, Michel;Xu, Qihong;Gale, Jennifer P.;Lewis, Michael;Campbell, Arthur J.;Schroeder, Frederick A.;Van de Bittner, Genevieve C.;Walk, Michelle;Amaya, Aldo;Su, Ping;Dordevic, Luka;Sacher, Joshua R.;Skepner, Adam;Fei, David;Dennehy, Kelly;Nguyen, Shannon;Faloon, Patrick W.;Perez, Jose;Cottrell, Jeffrey R.;Liu, Fang;Palmer, Michelle;Pan, Jen Q.;Hooker, Jacob M.;Zhang, Yan-Ling;Scolnick, Edward;Wagner, Florence F.;Holson, Edward B.. And the article was included in ACS Chemical Biology in 2018.Formula: C11H21NO3 This article mentions the following:

Schizophrenia is a severe neuropsychiatric disease that lacks completely effective and safe therapies. As a polygenic disorder, genetic studies have only started to shed light on its complex etiol. To date, the pos. symptoms of schizophrenia are well-managed by antipsychotic drugs, which primarily target the dopamine D2 receptor (D2R). However, these antipsychotics are often accompanied by severe side effects, including motoric symptoms. At D2R, antipsychotic drugs antagonize both G-protein dependent (Gα_i/o) signaling and G-protein independent (β-arrestin) signaling. However, the relevant contributions of the distinct D2R signaling pathways to antipsychotic efficacy and on-target side effects (motoric) are still incompletely understood. Recent evidence from mouse genetic and pharmacol. studies point to β-arrestin signaling as the major driver of antipsychotic efficacy and suggest that a β-arrestin biased D2R antagonist could achieve an addnl. level of selectivity at D2R, increasing the therapeutic index of next generation antipsychotics. Here, we characterize BRD5814, a highly brain penetrant β-arrestin biased D2R antagonist. BRD5814 demonstrated good target engagement via PET imaging, achieving efficacy in an amphetamine-induced hyperlocomotion mouse model with strongly reduced motoric side effects in a rotarod performance test. This proof of concept study opens the possibility for the development of a new generation of pathway selective antipsychotics at D2R with reduced side effect profiles for the treatment of schizophrenia. In the experiment, the researchers used many compounds, for example, 1-Boc-4-Hydroxy-4-methylpiperidine (cas: 406235-30-1Formula: C11H21NO3).

1-Boc-4-Hydroxy-4-methylpiperidine (cas: 406235-30-1) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N–H bond in an axial position, and the other in an equatorial position.Formula: C11H21NO3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Ni-catalyzed cross-electrophile coupling between vinyl/aryl and alkyl sulfonates: synthesis of cycloalkenes and modification of peptides was written by Duan, Jicheng;Du, Yun-Fei;Pang, Xiaobo;Shu, Xing-Zhong. And the article was included in Chemical Science in 2019.Application of 33439-27-9 This article mentions the following:

The coupling reactions between vinyl/aryl and alkyl C-O electrophiles that can be derived from chem. feedstocks and naturally occurring functional groups was reported. This method provided an efficient approach to the synthesis of a wide range of functionalized, and/or secondary alkyl substituted cycloalkenes that are difficult to synthesize by conventional methods. The reaction proceeded with broad substrate scope, and tolerated various functional groups such as alc., aldehyde, ketone, ester, amide, alkene, alkyne, heterocycles, organotin and organosilicon compounds The synthetic utility of this method was demonstrated by providing facile access to important building blocks. The possibility to apply this method for late-stage modification of peptides was also demonstrated. A broad range of functionalized alkyl groups was selectively introduced into tyrosine in peptides via C-C bond formation, which was a challenge to the existing procedures. In the experiment, the researchers used many compounds, for example, 1-Tosylpiperidin-4-one (cas: 33439-27-9Application of 33439-27-9).

1-Tosylpiperidin-4-one (cas: 33439-27-9) 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. Piperidine derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Application of 33439-27-9

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Orally bioavailable dual MMP-1/MMP-14 sparing, MMP-13 selective α-sulfone hydroxamates was written by Kolodziej, Stephen A.;Hockerman, Susan L.;Boehm, Terri L.;Carroll, Jeffery N.;DeCrescenzo, Gary A.;McDonald, Joseph J.;Mischke, Debbie A.;Munie, Grace E.;Fletcher, Theresa R.;Rico, Joseph G.;Stehle, Nathan W.;Swearingen, Craig;Becker, Daniel P.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2010.Electric Literature of C12H17NO This article mentions the following:

A series of Ph piperidine α-sulfone hydroxamate derivatives, e.g., I, has been prepared utilizing a combination of solution-phase and resin-bound library technologies to afford compounds that are potent and highly selective for MMP-13, are dual-sparing of MMP-1 and MMP-14 (MT1-MMP) and exhibit oral bioavailability in rats. In the experiment, the researchers used many compounds, for example, 4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8Electric Literature of C12H17NO).

4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. 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 C12H17NO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

1-, 3- And 8-substituted-9-deazaxanthines as potent and selective antagonists at the human A_2B adenosine receptor was written by Stefanachi, Angela;Brea, Jose Manuel;Cadavid, Maria Isabel;Centeno, Nuria B.;Esteve, Cristina;Loza, Maria Isabel;Martinez, Ana;Nieto, Rosa;Ravina, Enrique;Sanz, Ferran;Segarra, Victor;Sotelo, Eddy;Vidal, Bernat;Carotti, Angelo. And the article was included in Bioorganic & Medicinal Chemistry in 2008.Recommanded Product: 4-(2-Methoxyphenyl)piperidine This article mentions the following:

A large series of piperazin-, piperidin- and tetrahydroisoquinolinamides of 4-(1,3-dialkyl-9-deazaxanthin-8-yl)phenoxyacetic acid were prepared through conventional or multiple parallel syntheses and evaluated for their binding affinity at the recombinant human adenosine receptors, chiefly at the hA_2B and hA_2A receptor subtypes. Several ligands endowed with high binding affinity at hA_2B receptors, excellent selectivity over hA_2A and hA₃ and a significant, but lower, selectivity over hA₁ were identified. Among them, piperazinamide derivatives (I and II), and piperidinamide derivative (III) proved highly potent at hA_2B (K_i = 11, 2 and 5.5 nM, resp.) and selective towards hA_2A (hA_2A/hA_2B SI = 912, 159 and 630, resp.), hA₃ (hA₃/hA_2B SI = > 100, 3090 and >180, resp.) and hA₁ (hA₁/hA_2B SI = > 100, 44 and 120, resp.), SI being the selectivity index. A number of selected ligands tested in functional assays in vitro showed very interesting antagonist activities and efficacies at both A_2A and A_2B receptor subtypes, with pA₂ values close to the corresponding pK_is. Structure-affinity and structure-selectivity relationships suggested that the binding potency at the hA_2B receptor may be increased by lipophilic substituents at the N4-position of piperazinamides and that an ortho-methoxy substituent at the 8-Ph ring and alkyl groups at N1 larger than the ones at N3, in the 9-deazaxanthine ring, may strongly enhance the hA_2A/hA_2B SI. In the experiment, the researchers used many compounds, for example, 4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8Recommanded Product: 4-(2-Methoxyphenyl)piperidine).

4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8) 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. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Recommanded Product: 4-(2-Methoxyphenyl)piperidine

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Discovery of MAP855, an Efficacious and Selective MEK1/2 Inhibitor with an ATP-Competitive Mode of Action was written by Poddutoori, Ramulu;Aardalen, Kimberly;Aithal, Kiran;Barahagar, Sanjeev Surendranath;Belliappa, Charamanna;Bock, Mark;Chelur, Shekar;Gerken, Andrea;Gopinath, Sreevalsam;Gruenenfelder, Bjoern;Kiffe, Michael;Krishnaswami, Maithreyi;Langowski, John;Madapa, Sudharshan;Narayanan, Kishore;Pandit, Chetan;Panigrahi, Sunil Kumar;Perrone, Mark;Potakamuri, Ravi Kumar;Ramachandra, Murali;Ramanathan, Anuradha;Ramos, Rita;Sager, Emine;Samajdar, Susanta;Subramanya, Hosahalli S.;Thimmasandra, Devaraja Seethappa;Venetsanakos, Eleni;Mobitz, Henrik. And the article was included in Journal of Medicinal Chemistry in 2022.Formula: C9H19N3O2 This article mentions the following:

Mutations in MEK1/2 have been described as a resistance mechanism to BRAF/MEK inhibitor treatment. We report the discovery of a novel ATP-competitive MEK1/2 inhibitor with efficacy in wildtype (WT) and mutant MEK12 models. Starting from a HTS hit, we obtained selective, cellularly active compounds that showed equipotent inhibition of WT MEK1/2 and a panel of MEK1/2 mutant cell lines. Using a structure-based approach, the optimization addressed the liabilities by systematic anal. of mol. matched pairs (MMPs) and ligand conformation. Addition of only three heavy atoms to early tool compound 6 removed Cyp3A4 liabilities and increased the cellular potency by 100-fold, while reducing log P by 5 units. Profiling of MAP855, compound 30, in pharmacokinetic-pharmacodynamic and efficacy studies in BRAF-mutant models showed comparable efficacy to clin. MEK1/2 inhibitors. Compound 30 is a novel highly potent and selective MEK1/2 kinase inhibitor with equipotent inhibition of WT and mutant MEK1/2, whose drug-like properties allow further investigation in the mutant MEK setting upon BRAF/MEK therapy. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-aminopiperazine-1-carboxylate (cas: 118753-66-5Formula: C9H19N3O2).

tert-Butyl 4-aminopiperazine-1-carboxylate (cas: 118753-66-5) 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. 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.Formula: C9H19N3O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Silyl enol etherification by a Tf₂NH/amine co-catalytic system for minimizing hazardous waste generation was written by Kurahashi, Kei;Yamaoka, Yousuke;Takemoto, Yoshiji;Takasu, Kiyosei. And the article was included in Reaction Chemistry & Engineering in 2018.Computed Properties of C12H15NO3S This article mentions the following:

A practical silyl enol etherification of ketones with allylsilanes catalyzed by a Tf₂NH-amine co-catalyst under mild conditions has been developed. The reaction generated only volatile isobutene gas as waste. Moreover, a multi-gram synthesis using a microfluidic system and a domino silyl enol etherification-(2 + 2) cycloaddition reaction were demonstrated. In the experiment, the researchers used many compounds, for example, 1-Tosylpiperidin-4-one (cas: 33439-27-9Computed Properties of C12H15NO3S).

1-Tosylpiperidin-4-one (cas: 33439-27-9) 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 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 C12H15NO3S

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem