Category: piperidines

Discovery of BRD4 bromodomain inhibitors by fragment-based high-throughput docking was written by Zhao, Hongtao;Gartenmann, Lisa;Dong, Jing;Spiliotopoulos, Dimitrios;Caflisch, Amedeo. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2014.Quality Control of 1-Tosylpiperidin-4-one This article mentions the following:

Bromodomains (BRDs) recognize acetyl-lysine modified histone tails mediating epigenetic processes. BRD4, a protein containing two bromodomains, has emerged as an attractive therapeutic target for several types of cancer as well as inflammatory diseases. Using a fragment-based in silico screening approach, we identified two small mols. that bind to the first bromodomain of BRD4 with low-micromolar affinity and favorable ligand efficiency (0.37 kcal/mol per non-hydrogen atom), selectively over other families of bromodomains. Notably, the hit rate of the fragment-based in silico approach is about 10% as only 24 putative inhibitors, from an initial library of about 9 million mols., were tested in vitro. 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 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.Quality Control of 1-Tosylpiperidin-4-one

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Tertiary Alcohols as Radical Precursors for the Introduction of Tertiary Substituents into Heteroarenes was written by Pitre, Spencer P.;Muuronen, Mikko;Fishman, Dmitry A.;Overman, Larry E.. And the article was included in ACS Catalysis in 2019.Recommanded Product: 1-Boc-4-Hydroxy-4-methylpiperidine This article mentions the following:

Despite many recent advances in the radical alkylation of electron-deficient heteroarenes since the seminal reports by Minisci and co-workers, methods for the direct incorporation of tertiary alkyl substituents into nitrogen heteroarenes are limited. This report describes the use of tert-alkyl oxalate salts, derived from tertiary alcs., to introduce tertiary substituents into a variety of heterocyclic substrates. This reaction has reasonably broad scope, proceeds rapidly under mild conditions, and is initiated by either photochem. or thermal activation. Insights into the underlying mechanism of the higher yielding visible-light initiated process were obtained by flash photolysis studies, whereas computational studies provided insight into the reaction scope. 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 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.Recommanded Product: 1-Boc-4-Hydroxy-4-methylpiperidine

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

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

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

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

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

2-Phenylpyrroles as conformationally restricted benzamide analogs. A new class of potential antipsychotics. 2 was written by Van Wijngaarden, Ineke;Kruse, Chris G.;Van der Heyden, Jan A. M.;Tulp, Martin T. M.. And the article was included in Journal of Medicinal Chemistry in 1988.Synthetic Route of C12H17NO This article mentions the following:

A series of 2-phenylpyrrole Mannich bases I (R = H, 4-F, 4-CF₃, 4-CHMe₂, 3-Cl, 2-OMe, 2,6-F₂; R¹ = H, Me, Ph, CF₂CF₂CF₃, CH₂CH₂OH) and II (R² = H, F; X = NC₆H₄CF₃-3, NC₆H₄F-4, CHPh, CHC₆H₄OMe-2, etc.) was synthesized and screened in pharmacol. models for antipsychotic activity and extrapyramidal effects. Structure modifications of I (R¹ = 4-F, R² = H), the prototype of a new class of sodium-independent atypical dopamine D-2 antagonists, resultes in II (R² = F, X = imino-7-benzofuranyl) (III), which was an even more potent and selective D-2 antagonist than the parent compound The excellent oral activity in the apomorphine-induced climbing behavior and the conditioned avoidance response tests and the absence of catalepsy make III particularly promising as a potential antipsychotic with a low propensity to induce acute extrapyramidal side effects. In the experiment, the researchers used many compounds, for example, 4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8Synthetic Route of C12H17NO).

4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. 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.Synthetic Route of C12H17NO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Catalytic Asymmetric Homologation of 4-Substituted Cyclohexanones with CF₃CHN₂: Enantioselective Synthesis of α-Trifluoromethyl Cycloheptanones was written by Li, Shu-Sen;Sun, Shuo;Wang, Jianbo. And the article was included in Angewandte Chemie, International Edition in 2022.Computed Properties of C12H15NO3S This article mentions the following:

A catalytic asym. trifluoromethylation of cyclic ketones via a ScIII/chiral bisoxazoline-catalyzed homologation reaction by employing 2,2,2-trifluorodiazoethane (CF₃CHN₂) as the CF₃ source was reported. This desymmetrization process was highly efficient and generates two chiral centers with excellent diastereoselectivity and enantioselectivity, affording chiral α-trifluoromethyl cyclic ketones in a straightforward manner. 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 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.Computed Properties of C12H15NO3S

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Total synthesis of balanol: a potent protein kinase C inhibitor of fungal origin was written by Adams, C. P.;Fairway, S. M.;Hardy, C. J.;Hibbs, D. E.;Hursthouse, M. B.;Morley, A. D.;Sharp, B. W.;Vicker, N.;Warner, I.. And the article was included in Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry in 1995.Product Details of 33439-27-9 This article mentions the following:

The total synthesis of the fungal metabolite balanol, a potent inhibitor of protein kinase C, is described. The synthesis includes a novel synthesis of 3-amino-4-hydroxyazepanes via a directed ring expansion of 3-bromopiperidin-4-ones. 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. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Product Details of 33439-27-9

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem