Day: February 9, 2023

Discovery of GS-9973, a Selective and Orally Efficacious Inhibitor of Spleen Tyrosine Kinase was written by Currie, Kevin S.;Kropf, Jeffrey E.;Lee, Tony;Blomgren, Peter;Xu, Jianjun;Zhao, Zhongdong;Gallion, Steve;Whitney, J. Andrew;Maclin, Deborah;Lansdon, Eric B.;Maciejewski, Patricia;Rossi, Ann Marie;Rong, Hong;Macaluso, Jennifer;Barbosa, James;Di Paolo, Julie A.;Mitchell, Scott A.. And the article was included in Journal of Medicinal Chemistry in 2014.Safety of 4-Methylpiperidin-4-ol hydrochloride This article mentions the following:

Spleen tyrosine kinase (Syk) is an attractive drug target in autoimmune, inflammatory, and oncol. disease indications. The most advanced Syk inhibitor, R406, (or its prodrug form fostamatinib), has shown efficacy in multiple therapeutic indications, but its clin. progress has been hampered by dose-limiting adverse effects that have been attributed, at least in part, to the off-target activities of R406. It is expected that a more selective Syk inhibitor would provide a greater therapeutic window. Herein the authors report the discovery and optimization of a novel series of imidazo[1,2-a]pyrazine Syk inhibitors. This work culminated in the identification of GS-9973, a highly selective and orally efficacious Syk inhibitor which is currently undergoing clin. evaluation for autoimmune and oncol. indications. In the experiment, the researchers used many compounds, for example, 4-Methylpiperidin-4-ol hydrochloride (cas: 586375-35-1Safety of 4-Methylpiperidin-4-ol hydrochloride).

4-Methylpiperidin-4-ol hydrochloride (cas: 586375-35-1) 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 ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Safety of 4-Methylpiperidin-4-ol hydrochloride

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Catalytic C(sp²)-C(sp³) Bond Formation of Methoxyarenes by the Organic Superbase t-Bu-P4 was written by Shigeno, Masanori;Hayashi, Kazutoshi;Nozawa-Kumada, Kanako;Kondo, Yoshinori. And the article was included in Organic Letters in 2020.COA of Formula: C13H16N2 This article mentions the following:

The organic superbase catalyst t-Bu-P4 achieves nucleophilic aromatic substitution of methoxyarenes with alkanenitrile pronucleophiles. A variety of functional groups [cyano, nitro, (non)enolizable ketone, chloride, and amide moieties] are allowed on methoxyarenes. Moreover, an array of alkanenitriles with/without an aryl moiety at the nitrile α-position can be employed. The system also features no requirement of a stoichiometric base, MeOH (not salt waste) formation as a byproduct, and the production of congested quaternary carbon centers. In the experiment, the researchers used many compounds, for example, 1-Benzylpiperidine-4-carbonitrile (cas: 62718-31-4COA of Formula: C13H16N2).

1-Benzylpiperidine-4-carbonitrile (cas: 62718-31-4) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Piperidine derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.COA of Formula: C13H16N2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

6-Benzhydryl-4-amino-quinolin-2-ones as Potent Cannabinoid Type 1 (CB₁) Receptor Inverse Agonists and Chemical Modifications for Peripheral Selectivity was written by Zhang, Yue-Mei;Greco, Michael N.;Macielag, Mark J.;Teleha, Christopher A.;DesJarlais, Renee L.;Tang, Yuting;Ho, George;Hou, Cuifen;Chen, Cailin;Zhao, Shuyuan;Kauffman, Jack;Camacho, Raul;Qi, Jenson;Murray, William;Demarest, Keith;Leonard, James. And the article was included in Journal of Medicinal Chemistry in 2018.Application In Synthesis of 1-(Methylsulfonyl)piperidin-4-amine hydrochloride This article mentions the following:

A novel series of 6-benzhydryl-4-amino-quinolin-2-ones was discovered as cannabinoid type 1 receptor (CB₁R) inverse agonists based on the high-throughput screening hit, compound 1a. Structure-activity relationships were studied to improve in vitro/in vivo pharmacol. and restrict distribution to the peripheral circulation. We adopted several strategies such as increasing topol. polar surface area, incorporating discrete polyethylene glycol side chains, and targeting P-glycoprotein (P-gp) to minimize access to the brain. Compound 6a is a P-gp substrate and a potent and highly selective CB₁R inverse agonist, demonstrating excellent in vivo metabolic stability and a low brain to plasma ratio. However, brain receptor occupancy studies showed that compound 6a may accumulate in brain with repeat dosing. This was evidenced by compound 6a inhibiting food intake and inducing weight loss in diet-induced obese mice. Thus, a strategy based on P-gp efflux may not be adequate for peripheral restriction of the disclosed quinolinone series. In the experiment, the researchers used many compounds, for example, 1-(Methylsulfonyl)piperidin-4-amine hydrochloride (cas: 651057-01-1Application In Synthesis of 1-(Methylsulfonyl)piperidin-4-amine hydrochloride).

1-(Methylsulfonyl)piperidin-4-amine hydrochloride (cas: 651057-01-1) 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 ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Application In Synthesis of 1-(Methylsulfonyl)piperidin-4-amine hydrochloride

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

The Witkop-Winterfeldt oxidation converts tetrahydropyridoindoles into pyrroloquinolones and cinnolines by an unprecedented scaffold rearrangement was written by Mentel, Matthias;Peters, Martin;Albering, Joerg;Breinbauer, Rolf. And the article was included in Tetrahedron in 2011.Application of 33439-27-9 This article mentions the following:

The Fischer indole reaction between phenylhydrazines and N-tosyl-4-piperidone furnishes tetrahydropyrido[4,3-b]indoles. In a Witkop-Winterfeldt oxidation using ozone, such indole derivatives are converted into medium-sized dicarbonyl ring systems, which cyclize to pyrroloquinolones. A detailed study of the reaction intermediates and the characterization of a cinnoline betaine side product formed by an unprecedented ring closure mechanism are reported. 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. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. 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.Application of 33439-27-9

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Optimization of biaryloxazolidinone as promising antibacterial agents against antibiotic-susceptible and antibiotic-resistant gram-positive bacteria was written by Wu, Yachuang;Ding, Xiudong;Yang, Yifeng;Li, Yingxiu;Qi, Yinliang;Hu, Feng;Qin, Mingze;Liu, Yajing;Sun, Lu;Zhao, Yanfang. And the article was included in European Journal of Medicinal Chemistry in 2020.Formula: C9H19N3O2 This article mentions the following:

Herein, novel biaryloxazolidinone analogs I [X = O, S, NMe, etc.; Y = N, CH, CHOH, etc.; Z = N, CH] were designed and synthesized to improve the chem. and metabolic stability. Compounds I [X = S, NMe, SO₂; Y = N, CHOH; Z = CH] showed significant antibacterial activity against the tested Gram-pos. bacteria as compared to radezolid and linezolid. Further studies indicated that most of them exhibited improved water solubility and chem. stability. Compound I [X = SO₂; Y = N; Z = CH] had MIC values of 0.125-0.25 μg/mL against all tested Gram-pos. bacteria, and showed excellent antibacterial activity against clin. isolates of antibiotic-susceptible and antibiotic-resistant bacteria. Moreover, it was stable in human liver microsome. From a safety viewpoint, it showed non-cytotoxic activity against hepatic cell and exhibited lower inhibitory activity against human MAO-A compared to linezolid. The potent antibacterial activity and all these improved drug-likeness properties and safety profile suggested that compound I [X = SO₂; Y = N; Z = CH] might be a promising drug candidate for further investigation. 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.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.Formula: C9H19N3O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem