Day: January 3, 2023

Discovery of CDZ173 (Leniolisib), Representing a Structurally Novel Class of PI3K Delta-Selective Inhibitors was written by Hoegenauer, Klemens;Soldermann, Nicolas;Zecri, Frederic;Strang, Ross S.;Graveleau, Nadege;Wolf, Romain M.;Cooke, Nigel G.;Smith, Alexander B.;Hollingworth, Gregory J.;Blanz, Joachim;Gutmann, Sascha;Rummel, Gabriele;Littlewood-Evans, Amanda;Burkhart, Christoph. And the article was included in ACS Medicinal Chemistry Letters in 2017.Related Products of 4045-22-1 This article mentions the following:

The predominant expression of phosphoinositide 3-kinase δ (PI3Kδ) in leukocytes and its critical role in B and T cell functions led to the hypothesis that selective inhibitors of this isoform would have potential as therapeutics for the treatment of allergic and inflammatory disease. Targeting specifically PI3Kδ should avoid potential side effects associated with the ubiquitously expressed PI3Kα and β isoforms. We disclose how morphing the heterocyclic core of previously discovered 4,6-diaryl quinazolines to a significantly less lipophilic 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine, followed by replacement of one of the Ph groups with a pyrrolidine-3-amine, led to a compound series with an optimal on-target profile and good ADME properties. A final lipophilicity adjustment led to the discovery of CDZ173 (leniolisib), a potent PI3Kδ selective inhibitor with suitable properties and efficacy for clin. development as an anti-inflammatory therapeutic. In vitro, CDZ173 inhibits a large spectrum of immune cell functions, as demonstrated in B and T cells, neutrophils, monocytes, basophils, plasmocytoid dendritic cells, and mast cells. In vivo, CDZ173 inhibits B cell activation in rats and monkeys in a concentration- and time-dependent manner. After prophylactic or therapeutic dosing, CDZ173 potently inhibited antigen-specific antibody production and reduced disease symptoms in a rat collagen-induced arthritis model. Structurally, CDZ173 differs significantly from the first generation of PI3Kδ and PI3Kγδ-selective clin. compounds Therefore, CDZ173 could differentiate by a more favorable safety profile. CDZ173 is currently in clin. studies in patients suffering from primary Sjogren’s syndrome and in APDS/PASLI, a disease caused by gain-of-function mutations of PI3Kδ. In the experiment, the researchers used many compounds, for example, 1-(4-Hydroxypiperidin-1-yl)ethanone (cas: 4045-22-1Related Products of 4045-22-1).

1-(4-Hydroxypiperidin-1-yl)ethanone (cas: 4045-22-1) 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.Related Products of 4045-22-1

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Hindered dialkyl ether synthesis with electrogenerated carbocations was written by Xiang, Jinbao;Shang, Ming;Kawamata, Yu;Lundberg, Helena;Reisberg, Solomon H.;Chen, Miao;Mykhailiuk, Pavel;Beutner, Gregory;Collins, Michael R.;Davies, Alyn;Del Bel, Matthew;Gallego, Gary M.;Spangler, Jillian E.;Starr, Jeremy;Yang, Shouliang;Blackmond, Donna G.;Baran, Phil S.. And the article was included in Nature (London, United Kingdom) in 2019.Recommanded Product: 406235-30-1 This article mentions the following:

Hindered ethers are of high value for various applications; however, they remain an underexplored area of chem. space because they are difficult to synthesize via conventional reactions. Such motifs are highly coveted in medicinal chem., because extensive substitution about the ether bond prevents unwanted metabolic processes that can lead to rapid degradation in vivo. Here we report a simple route towards the synthesis of hindered ethers, in which electrochem. oxidation is used to liberate high-energy carbocations from simple carboxylic acids. These reactive carbocation intermediates, which are generated with low electrochem. potentials, capture an alc. donor under non-acidic conditions; this enables the formation of a range of ethers (more than 80 have been prepared here) that would otherwise be difficult to access. The carbocations can also be intercepted by simple nucleophiles, leading to the formation of hindered alcs. and even alkyl fluorides. This method was evaluated for its ability to circumvent the synthetic bottlenecks encountered in the preparation of 12 chem. scaffolds, leading to higher yields of the required products, in addition to substantial reductions in the number of steps and the amount of labor required to prepare them. The use of mol. probes and the results of kinetic studies support the proposed mechanism and the role of additives under the conditions examined The reaction manifold that we report here demonstrates the power of electrochem. to access highly reactive intermediates under mild conditions and, in turn, the substantial improvements in efficiency that can be achieved with these otherwise-inaccessible intermediates. In the experiment, the researchers used many compounds, for example, 1-Boc-4-Hydroxy-4-methylpiperidine (cas: 406235-30-1Recommanded Product: 406235-30-1).

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 derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Recommanded Product: 406235-30-1

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Rhodium(III)-Catalyzed Cyclopropanation of Unactivated Olefins Initiated by C-H Activation was written by Phipps, Erik J. T.;Piou, Tiffany;Rovis, Tomislav. And the article was included in Synlett in 2019.Quality Control of 1-Tosylpiperidin-4-one This article mentions the following:

A rhodium(III)-catalyzed cyclopropanation of unactivated olefins and N-enoxyphthalimides initiated by an alkenyl C-H activation was developed to afford the corresponding products I [R = Ph, CH₂Bn, 2-naphthyl, etc.; R¹ = Et; R¹R¹ = CH₂C(CN)₂CH₂, (CH₂)₄, (CH₂)₅, etc.] in good yields. A variety of 1,1-disubstituted olefins undergo efficient cyclopropanation with a slight excess of alkene stoichiometry. A series of mechanistic interrogations implicated a metal carbene as an intermediate. In the experiment, the researchers used many compounds, for example, 1-Tosylpiperidin-4-one (cas: 33439-27-9Quality Control of 1-Tosylpiperidin-4-one).

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. 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.Quality Control of 1-Tosylpiperidin-4-one

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Discovery of tetrahydropyrido[4,3-d]pyrimidine derivatives for the treatment of neuropathic pain was written by Sharma, Monika;Deekshith, Vanamala;Semwal, Arvind;Sriram, Dharmarajan;Yogeeswari, Perumal. And the article was included in Bioorganic Chemistry in 2014.Recommanded Product: 1-Tosylpiperidin-4-one This article mentions the following:

A series of tetrahydropyridopyrimidine derivatives were synthesized and evaluated for neurotoxicity and peripheral analgesic activity followed by assessment of antiallodynic and antihyperalgesic potential in two peripheral neuropathic pain models, the chronic constriction injury (CCI) and partial sciatic nerve ligation (PSNL). Compounds (4b and 4d) exhibiting promising efficacies in four behavioral assays of allodynia and hyperalgesia (spontaneous pain, tactile allodynia, cold allodynia and mech. hyperalgesia) were quantified for their ED₅₀ values (15.12-65.10 mg/kg). Studies carried out to assess the underlying mechanism revealed that the compounds suppressed the inflammatory component of the neuropathic pain and prevented oxidative and nitrosative stress. In the experiment, the researchers used many compounds, for example, 1-Tosylpiperidin-4-one (cas: 33439-27-9Recommanded Product: 1-Tosylpiperidin-4-one).

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 are being utilized in different ways as anticancer, antiviral, antimalarial, antimicrobial, antifungal, antihypertension, analgesic, anti-inflammatory, anti-Alzheimer, antipsychotic and/or anticoagulant agents.Recommanded Product: 1-Tosylpiperidin-4-one

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Design, synthesis and biological evaluation of novel thiazole-based derivatives as human Pin1 inhibitors was written by Du, Lifei;Wang, Xiaoyu;Cui, Guonan;Xu, Bailing. And the article was included in Bioorganic & Medicinal Chemistry in 2021.Recommanded Product: 4-Methylpiperidin-4-ol hydrochloride This article mentions the following:

Pin1 is a peptidyl prolyl cis-trans isomerase (PPIase) and inhibiting Pin1 is a potential way for discovering anti-tumor agents. With an aim to find potent Pin1 inhibitors with a novel scaffold, a series of thiazole derivatives with an alicyclic heterocycles on the 2-position were designed, synthesized and tested against human Pin1. Compound 9p bearing a 2-oxa-6-azaspiro [3,3] heptane moiety on the thiazole scaffold was identified as the most potent Pin1 inhibitor of this series with an IC50 value of 0.95μM. The structure-activity relationship (SAR) and mol. modeling study indicated that introducing an alicyclic ring with an H-bond acceptor would be a viable way to improve the binding affinity. In the experiment, the researchers used many compounds, for example, 4-Methylpiperidin-4-ol hydrochloride (cas: 586375-35-1Recommanded Product: 4-Methylpiperidin-4-ol hydrochloride).

4-Methylpiperidin-4-ol hydrochloride (cas: 586375-35-1) 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.Recommanded Product: 4-Methylpiperidin-4-ol hydrochloride

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Synthesis and biological effects of a new series of 2-amino-3-benzoylthiophenes as allosteric enhancers of A₁-adenosine receptor was written by Baraldi, P. G.;Zaid, A. Z.;Lampronti, I.;Fruttarolo, F. F.;Pavani, M. G.;Tabrizi, M. A.;Shryock, J. C. S.;Leung, E.;Romagnoli, R.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2000.Product Details of 33439-27-9 This article mentions the following:

New derivatives of PD 81,723, an allosteric enhancer of agonist binding to the A₁-adenosine receptor, have been synthesized and evaluated in an intact cell assay. Compounds I (R¹-R³ = H; R¹ = 4-Cl, 4-Br, R²R³ = (CH₂)₄) appeared to be more potent than PD 81,723 and at a concentration of 0.1 μM caused significant reductions of cAMP content of CHO cells expressing the human A₁-adenosine receptor. Compounds II (R¹ = 4-Cl, R⁴ = PhCH₂CH₂, CH₂CO₂Et) appeared to be allosteric enhancers at a low concentration and antagonists at a higher concentration, whereas compounds I (R¹ = H, R² = R³ = Me; R²R³ = CH₂CH₂S; (CH₂)₅) and II (R¹ = H, R⁴ = 4-O₂NC₆H₄CH₂CH₂) appeared to be weak antagonists that are also allosteric enhancers at the higher concentration of 10 μM. In the experiment, the researchers used many compounds, for example, 1-Tosylpiperidin-4-one (cas: 33439-27-9Product Details of 33439-27-9).

1-Tosylpiperidin-4-one (cas: 33439-27-9) 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.Product Details of 33439-27-9

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Synthesis and bioactivity of new amides and ureas from 2-amino-5-(1-R-phenylsulfonyl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridines was written by Pavlova, A. S.;Yakunina, I. E.;Shumskii, A. N.;Shakhkel’dyan, I. V.;Atroshchenko, Yu. M.;Kobrakov, K. I.. And the article was included in Izvestiya Vysshikh Uchebnykh Zavedenii, Khimiya i Khimicheskaya Tekhnologiya in 2010.Application of 33439-27-9 This article mentions the following:

Hantzsch cyclization of N-(arylsulfonyl)-3-bromo-5-piperidinones (aryl = R¹ = Ph, 4-MeC₆H₄, 4-MeOC₆H₄), available in 2 steps from 4-piperidinone hydrochloride and arylsulfonyl chlorides, with thiourea afforded the corresponding tetrahydrothiazolo[5,4-c]pyridines I (R² = H) in 60-65% yields. Subsequent reactions of the latter with carboxylic acids in the presence of carbonyldiimidazole or with isocyanates gave the combinatorial libraries of amides I (R² = n-PrCO, PhCO, etc.) or ureas I (R² = 2-EtOC₆H₄NHCO, 3,4-Me₂C₆H₄NHCO, etc.), resp. The antimicrobial activity of some amides and ureas towards Escherichia coli and Agrobacterium tumefaciens was evaluated. 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. 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 33439-27-9

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Substitution of α-azido ethers with Grignard reagents and its use in combinatorial chemistry was written by Baruah, Mukulesh;Bols, Mikael. And the article was included in Journal of the Chemical Society, Perkin Transactions 1 in 2002.COA of Formula: C7H13NO2 This article mentions the following:

α-Azidobenzyl ethers reacted with alkyl or aryl Grignard reagents in toluene to produce α-alkylbenzyl or diarylmethyl ethers in 82-94% yield. α-Azidobenzyl ethers also reacted with multicomponent Grignard reagents to produce libraries of α-alkylbenzyl ethers. In the experiment, the researchers used many compounds, for example, 1-(4-Hydroxypiperidin-1-yl)ethanone (cas: 4045-22-1COA of Formula: C7H13NO2).

1-(4-Hydroxypiperidin-1-yl)ethanone (cas: 4045-22-1) 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 α-glucosidase inhibitors. The former are analogs of DNJ with an improved α-glucosidase inhibitory profile than that of DNJ. Boisson et al.COA of Formula: C7H13NO2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Nontraditional Fragment Couplings of Alcohols and Carboxylic Acids: C(sp³)-C(sp³) Cross-Coupling via Radical Sorting was written by Sakai, Holt A.;MacMillan, David W. C.. And the article was included in Journal of the American Chemical Society in 2022.Related Products of 406235-30-1 This article mentions the following:

In this report, the C(sp³)-C(sp³) cross-coupling of alcs. and carboxylic acids through the dual combination of N-heterocyclic carbene (NHC)-mediated deoxygenation and hypervalent iodine-mediated decarboxylation were described. This mild and practical Ni-catalyzed radical-coupling protocol was employed to prepare a wide array of alkyl-alkyl cross-coupled products, including highly congested quaternary carbon centers from the corresponding tertiary alcs. or tertiary carboxylic acids. Synthetic applications of this methodol. to alc. C1-alkylation and formal homologation, as well as to the late-stage functionalization of drugs, natural products, and biomols. were demonstrated. In the experiment, the researchers used many compounds, for example, 1-Boc-4-Hydroxy-4-methylpiperidine (cas: 406235-30-1Related Products of 406235-30-1).

1-Boc-4-Hydroxy-4-methylpiperidine (cas: 406235-30-1) 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. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising α-glucosidase inhibitors. The former are analogs of DNJ with an improved α-glucosidase inhibitory profile than that of DNJ. Boisson et al.Related Products of 406235-30-1

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Microwave-promoted amination of 3-bromoisoxazoles was written by Moore, Jane E.;Spinks, Daniel;Harrity, Joseph P. A.. And the article was included in Tetrahedron Letters in 2004.Recommanded Product: 58333-75-8 This article mentions the following:

Amination of 3-bromoisoxazoles, by a nucleophilic aromatic substitution reaction, is described. 3-Bromoisoxazoles were found to be inert to substitution under thermal conditions, however, the employment of phosphazene bases under microwave irradiation facilitated the amination process and allowed 3-aminoisoxazoles, e.g., I, to be isolated in moderate yields. In the experiment, the researchers used many compounds, for example, 4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8Recommanded Product: 58333-75-8).

4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8) 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.Recommanded Product: 58333-75-8

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem