Month: January 2023

Direct Construction of Quaternary Carbons from Tertiary Alcohols via Photoredox-Catalyzed Fragmentation of tert-Alkyl N-Phthalimidoyl Oxalates was written by Lackner, Gregory L.;Quasdorf, Kyle W.;Overman, Larry E.. And the article was included in Journal of the American Chemical Society in 2013.Recommanded Product: 1-Boc-4-Hydroxy-4-methylpiperidine This article mentions the following:

A convenient method for the direct construction of quaternary carbons from tertiary alcs. by visible-light photoredox coupling of tert-alkyl N-phthalimidoyl oxalate intermediates with electron-deficient alkenes is reported. In the experiment, the researchers used many compounds, for example, 1-Boc-4-Hydroxy-4-methylpiperidine (cas: 406235-30-1Recommanded Product: 1-Boc-4-Hydroxy-4-methylpiperidine).

1-Boc-4-Hydroxy-4-methylpiperidine (cas: 406235-30-1) 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. 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.Recommanded Product: 1-Boc-4-Hydroxy-4-methylpiperidine

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Discovery of 1-Butyl-3-chloro-4-(4-phenyl-1-piperidinyl)-(1H)-pyridone (JNJ-40411813): A Novel Positive Allosteric Modulator of the Metabotropic Glutamate 2 Receptor was written by Cid, Jose Maria;Tresadern, Gary;Duvey, Guillaume;Lutjens, Robert;Finn, Terry;Rocher, Jean-Philippe;Poli, Sonia;Vega, Juan Antonio;de Lucas, Ana Isabel;Matesanz, Encarnacion;Linares, Maria Lourdes;Andres, Jose Ignacio;Alcazar, Jesus;Alonso, Jose Manuel;Macdonald, Gregor J.;Oehlrich, Daniel;Lavreysen, Hilde;Ahnaou, Abdelah;Drinkenburg, Wilhelmus;Mackie, Claire;Pype, Stefan;Gallacher, David;Trabanco, Andres A.. And the article was included in Journal of Medicinal Chemistry in 2014.Recommanded Product: 4-(2-Methoxyphenyl)piperidine This article mentions the following:

The authors previously reported the discovery of 4-aryl-substituted pyridones with mGlu2 PAM activity starting from the HTS hit I. In this article, the authors describe a different exploration I from that led to the discovery of a novel subseries of phenylpiperidine-substituted pyridones. The optimization strategy involved the introduction of different spacers between the pyridone core and the Ph ring of I. The fine tuning of metabolism and hERG followed by differentiation of advanced leads that were identified on the basis of PK profiles and in vivo potency converged on lead compound II (JNJ-40411813). Full in vitro and in vivo profiles indicate that II displayed an optimal interplay between potency, selectivity, favorable ADMET/PK and cardiovascular safety profile, and central EEG activity. Compound II has been investigated in the clinic for schizophrenia and anxious depression disorders. 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. 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: 4-(2-Methoxyphenyl)piperidine

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Regioselective Arylboration of Isoprene and Its Derivatives by Pd/Cu Cooperative Catalysis was written by Smith, Kevin B.;Brown, M. Kevin. And the article was included in Journal of the American Chemical Society in 2017.Computed Properties of C12H15NO3S This article mentions the following:

A method for the regioselective arylboration of isoprene and its derivatives is presented. These reactions allow for the synthesis of useful building blocks from simple components. Through these studies, an unusual additive effect with DMAP was uncovered that allows for altered reactivity and the formation of quaternary C centers. The utility of this method is demonstrated toward the formal synthesis of mesembrine. 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. Piperidine derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Computed Properties of C12H15NO3S

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

2,4-Diamino-6,7-dimethoxyquinazolines. 4. 2-[4-(Substituted oxyethoxy)piperidino] derivatives as α₁-adrenoceptor antagonists and antihypertensive agents was written by Campbell, Simon F.;Danilewicz, John C.;Greengrass, Colin W.;Plews, Rhona M.. And the article was included in Journal of Medicinal Chemistry in 1988.Application of 4045-22-1 This article mentions the following:

A series of piperidinoquinazolines I (R = H, Ph, R¹ = H, Me, R² = H, Me, Ph, R³ = H, Me, Ph, Bu, CHMe₂, cyclopentyl) were prepared and evaluated for α-adrenoceptor affinity and antihypertensive activity. Most I showed binding affinities within the nM range for α₁-receptors, although I (R = R¹ = R³ = H, R² = Ph; R = H, R¹ = Me, R² = Ph, R³ = Et) showed enhanced potency (K_i, ca. 1.5 × 10^-10M), equivalent to that of prazosin. I also displaced [³H]clonidine from α₂-adrenoceptors, but at relatively high doses of 10^-6M, and selectivity for α₁ sites still predominated. In a rabbit pulmonary artery preparation, I (R = R¹ = R² = H, R³ = Et, Ph; R = H, R¹ = Me, R² = Ph, R³ = Et) were potent antagonists of the α₁-mediated, postjunctional vasoconstrictor activity of norepinephrine with no effect at the prejunctional α₂ sites which modulate transmitter release. Physicochem. measurements gave a pK_a of 7.63 ± 0.10 for I (R = R¹ = R² = H, R³ = Et) and N-1 protonation will be favored (60%) at physiol. pH to provide the α₁-adrenoceptor pharmacophore. Antihypertensive activity of I was evaluated following oral administration to spontaneously hypertensive rats, and blood pressure was measured after 1 and 6 h. I (R = R¹ = R² = H, R³ = Et, Bu, Ph; R = R³ = H, R¹ = Me, R² = Ph; R = Ph, R¹ = R² = H, R³ = Et) displayed moderate efficacy and duration of action in lowering blood pressure, but the plasma half-life (ca. 2 h) of I (R = R¹ = R² = H, R³ = Ph) in dogs was not compatible with potential once-daily administration in humans. In the experiment, the researchers used many compounds, for example, 1-(4-Hydroxypiperidin-1-yl)ethanone (cas: 4045-22-1Application of 4045-22-1).

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

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

First-Time Disclosure of CVN424, a Potent and Selective GPR6 Inverse Agonist for the Treatment of Parkinson’s Disease: Discovery, Pharmacological Validation, and Identification of a Clinical Candidate was written by Sun, Huikai;Monenschein, Holger;Schiffer, Hans H.;Reichard, Holly A.;Kikuchi, Shota;Hopkins, Maria;Macklin, Todd K.;Hitchcock, Stephen;Adams, Mark;Green, Jason;Brown, Jason;Murphy, Sean T.;Kaushal, Nidhi;Collia, Deanna R.;Moore, Steve;Ray, William J.;Carlton, Mark Beresford Lewis;Brice, Nicola L.. And the article was included in Journal of Medicinal Chemistry in 2021.Computed Properties of C11H13F2NO This article mentions the following:

Parkinson’s disease (PD) is a chronic and progressive movement disorder with the urgent unmet need for efficient symptomatic therapies with fewer side effects. GPR6 is an orphan G-protein coupled receptor (GPCR) with highly restricted expression in dopamine receptor D2-type medium spiny neurons (MSNs) of the indirect pathway, a striatal brain circuit which shows aberrant hyperactivity in PD patients. Potent and selective GPR6 inverse agonists (IAG) were developed starting from a low-potency screening hit (EC₅₀ = 43μM). Herein, we describe the multiple parameter optimization that led to the discovery of multiple nanomolar potent and selective GPR6 IAG, including our clin. compound CVN424 (I). GPR6 IAG reversed haloperidol-induced catalepsy in rats and restored mobility in the bilateral 6-OHDA-lesioned rat PD model demonstrating that inhibition of GPR6 activity in vivo normalizes activity in basal ganglia circuitry and motor behavior. CVN424 is currently in clin. development to treat motor symptoms in Parkinson’s disease. In the experiment, the researchers used many compounds, for example, 4-(2,4-Difluorophenoxy)piperidine (cas: 367501-08-4Computed Properties of C11H13F2NO).

4-(2,4-Difluorophenoxy)piperidine (cas: 367501-08-4) 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. 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.Computed Properties of C11H13F2NO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

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