Category: piperidines

Design and characterization of cereblon-mediated androgen receptor proteolysis-targeting chimeras was written by Takwale, Akshay D.;Jo, Seung-Hyun;Jeon, Yeong Uk;Kim, Hyung Soo;Shin, Choong Hoon;Lee, Heung Kyoung;Ahn, Sunjoo;Lee, Chong Ock;Du Ha, Jae;Kim, Jeong-Hoon;Hwang, Jong Yeon. And the article was included in European Journal of Medicinal Chemistry in 2020.Computed Properties of C10H20ClNO2 This article mentions the following:

Proteolysis-targeting chimera (PROTAC)-mediated protein degradation is a rapidly emerging therapeutic intervention that induces the degradation of targeted proteins. Herein, we report the design and biol. evaluation of a series of androgen receptor (AR) PROTAC degraders for the treatment of metastatic castration-resistant prostate cancer. Predominantly, instead of thalidomide, we utilized the TD-106 scaffold, a novel cereblon (CRBN) binder that was identified in our previous study. Our results suggest that the linker position in the TD-106 CRBN binder is critical for the efficiency of AR degradation The compounds attached to the 6-position of TD-106 promoted better degradation of AR than those at the 5- and 7-positions. Among the synthesized AR PROTACs, the representative degrader 33c (TD-802) effectively induced AR protein degradation, with a degradation concentration 50% of 12.5 nM and a maximum degradation of 93% in LNCaP prostate cancer cells. Addnl., most AR PROTAC degraders, including TD-802, displayed good liver microsomal stability and in vivo pharmacokinetic properties. Finally, we showed that TD-802 effectively inhibited tumor growth in an in vivo xenograft study. In the experiment, the researchers used many compounds, for example, tert-Butyl piperidine-4-carboxylate hydrochloride (cas: 892493-65-1Computed Properties of C10H20ClNO2).

tert-Butyl piperidine-4-carboxylate hydrochloride (cas: 892493-65-1) 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.Computed Properties of C10H20ClNO2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

The Banert cascade: A synthetic sequence to polyfunctional NH-1,2,3-triazoles was written by Loren, Jon C.;Sharpless, K. Barry. And the article was included in Synthesis in 2005.Quality Control of 1-Tosylpiperidin-4-one This article mentions the following:

A series of polyfunctional NH-1,2,3-triazoles, e.g., I, were prepared directly from propargyl halides and nucleophiles using a powerful, albeit little appreciated, synthetic sequence called the Banert cascade. Propargyl azides, prepared in situ from propargyl halides or sulfonates, underwent a thermal rearrangement sequence to triazafulvene intermediates, potent electrophiles, which were readily captured by diverse nucleophiles. Using this cascade, a series of racemic azidomethyl(hydroxymethyl)-NH-1,2,3-triazoles were prepared by a two-step protocol that commences with the addition of propargyl chloride to aldehydes and ketones. 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. 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. Piperidine derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Quality Control of 1-Tosylpiperidin-4-one

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Synthesis of metabolism-resistant substrates for the transport system for cationic amino acids. Their stimulation of the release of insulin and glucagon, and of the urinary loss of amino acids related to cystinuria was written by Christensen, Halvor N.;Cullen, Andrea M.. And the article was included in Biochimica et Biophysica Acta, Biomembranes in 1973.Recommanded Product: 33439-27-9 This article mentions the following:

Renal tubular transport (resorption) of citrulline [372-75-8] in rats did not occur by the same system serving for the basic amino acids or by the system serving for cystine [56-89-3], despite observed interactions in the resorption of these amino acids. Administration i.p. of the cationic arginine analog DL-1-guanyl-4-piperidineglycine (I) [41021-57-2] (5 mmoles/kg) selectively increased urinary excretion (i.e. inhibited resorption) of citrulline compared to that of basic amino acids (lysine [56-87-1], ornithine [70-26-8], arginine [74-79-3]). 4-Amino-1-guanylpiperidine-4-carboxylic acid (II) [31364-50-8] increased excretion of both citrulline and basic amino acids, and the citrulline analog 4-amino-1-carbamoylpiperidine-4-carboxylic acid (III) [40951-38-0], which did exist in cationic form, also increased the excretion of basic amino acids. I, II, and III increased cystine excretion, with I having the least effect. 4-Aminopiperidine-4-carboxylic acid (IV) [40951-39-1] and 4-piperidineglycine (V) [40951-40-4], like I, stimulated mainly citrulline excretion, and had little effect on excretion of basic amino acids or cystine. A mutual inhibitory interaction between citrulline and the basic amino acids not based on a shared transport route was postulated. Citrulline lost may thus be causally related to the loss of other amino acids in cystinuria. I, II, and homoarginine [156-86-5] mimicked the action of arginine and lysine and stimulated the release of insulin [9004-10-8] and glucagon [9007-92-5] from the pancreas in rats in vivo. II-V were metabolized slowly or not at all by the rat. Excretion of II-V was biphasic, with 43-63% of the dose lost during the 1st 6 hr and the hourly loss declining exponentially thereafter with a half-life varying from 10 hr for IV to 46 hr for II. Preparation of IV by the Strecker synthesis, its guanylation and carbamoylation to II and III, resp., and the radioactive labeling of several compounds were described, along with the synthesis of 1,4-diaminocyclohexane-1-carboxylic acid [40951-41-5], used in studies reported elsewhere. In the experiment, the researchers used many compounds, for example, 1-Tosylpiperidin-4-one (cas: 33439-27-9Recommanded Product: 33439-27-9).

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.Recommanded Product: 33439-27-9

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Discovery of 2-(4-Pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole (ABT-724), a Dopaminergic Agent with a Novel Mode of Action for the Potential Treatment of Erectile Dysfunction was written by Cowart, Marlon;Latshaw, Steven P.;Bhatia, Pramila;Daanen, Jerome F.;Rohde, Jeffrey;Nelson, Sherry L.;Patel, Meena;Kolasa, Teodozyi;Nakane, Masaki;Uchic, Marie E.;Miller, Loan N.;Terranova, Marc A.;Chang, Renjie;Donnelly-Roberts, Diana L.;Namovic, Marian T.;Hollingsworth, Peter R.;Martino, Brenda R.;Lynch, James J. III;Sullivan, James P.;Hsieh, Gin C.;Moreland, Robert B.;Brioni, Jorge D.;Stewart, Andrew O.. And the article was included in Journal of Medicinal Chemistry in 2004.Recommanded Product: 58333-75-8 This article mentions the following:

A new class of agents with potential utility for the treatment of erectile dysfunction has been discovered, guided by the hypothesis that selective D₄ agonists are erectogenic but devoid of the side effects typically associated with dopaminergic agents. The lead agent 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole (1, ABT-724) was discovered by optimization of a series of benzimidazole arylpiperazines. This highly selective D₄ agonist was found to be very potent and efficacious in vivo, eliciting penile erections in rats at a dose of 0.03 μmol/kg, with a pos. response rate of 77% erectile incidence. Even at high doses, it was devoid of side effects in animal models of central nervous system behaviors, emesis, or nausea. The structure-activity relationship of the parent benzimidazole series leading to 1 is described, with the detailed in vitro and in vivo profiles described. Distinctive structural features were discovered that are associated with D₄ selective agonism in this series of analogs. 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. 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.Recommanded Product: 58333-75-8

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Discovery and optimization of novel, non-steroidal glucocorticoid receptor modulators was written by Ray, Nicholas C.;Clark, Robin D.;Clark, David E.;Williams, Karen;Hickin, H. G.;Crackett, Peter H.;Dyke, Hazel J.;Lockey, Peter M.;Wong, Melanie;Devos, Rene;White, Anne;Belanoff, Joseph K.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2007.Reference of 58333-75-8 This article mentions the following:

A virtual screening approach comprising a 3-D similarity search based on known GR modulators was used to identify a novel series of non-steroidal glucocorticoid receptor (GR) antagonists. Optimization of the initial hit to provide potent compounds which exhibit good selectivity against other steroidal nuclear hormone receptors is described. In the experiment, the researchers used many compounds, for example, 4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8Reference of 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. Piperidine derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Reference of 58333-75-8

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Synthesis of substituted 4-azaisoindoles – New tacrine analogues was written by Bekolo, Henri;Kirsch, Gilbert. And the article was included in Canadian Journal of Chemistry in 2007.Safety of 1-Tosylpiperidin-4-one This article mentions the following:

The regioselective Friedlaender reaction of 3-amino-4-cyanopyrroles with a series of cyclic ketones has enabled the first reported synthesis of substituted 4-azaisoindoles, e.g. I. Structurally, this new class of compounds stands for the first reported 4-azaisoindole tacrine analogs. A reaction mechanism for the formation of the reported 4-azaisoindoles is proposed. In the experiment, the researchers used many compounds, for example, 1-Tosylpiperidin-4-one (cas: 33439-27-9Safety of 1-Tosylpiperidin-4-one).

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.Safety of 1-Tosylpiperidin-4-one

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

New neurogenic lipoic-based hybrids as innovative Alzheimer’s drugs with σ-1 agonism and β-secretase inhibition was written by Estrada, Martin;Perez, Concepcion;Soriano, Elena;Laurini, Erik;Romano, Maurizio;Pricl, Sabrina;Morales-Garcia, Jose A.;Perez-Castillo, Ana;Rodriguez-Franco, Maria Isabel. And the article was included in Future Medicinal Chemistry in 2016.SDS of cas: 62718-31-4 This article mentions the following:

Background: Neurogenic agents emerge as innovative drugs for the treatment of Alzheimer’s disease (AD), whose pathol. complexity suggests strengthening research in the multi-target directed ligands strategy. Results: By combining the lipoic acid structure with N-benzylpiperidine or N,N-dibenzyl(N-methyl)amine fragments, new multi-target directed ligands were obtained that act at three relevant targets in AD: σ-1 receptor (σ₁R), β-secretase-1 (BACE1) and acetylcholinesterase (AChE). Moreover, they show potent neurogenic properties, good antioxidant capacity and favorable CNS permeability. Mol. modeling studies on AChE, σ₁R and BACE1 highlight relevant drug-protein interactions that may contribute to the development of new disease-modifying drugs. Conclusion: New lipoic-based σ₁ agonists endowed with neurogenic, antioxidant, cholinergic and amyloid β-peptide-reducing properties have been discovered for the potential treatment of AD. In the experiment, the researchers used many compounds, for example, 1-Benzylpiperidine-4-carbonitrile (cas: 62718-31-4SDS of cas: 62718-31-4).

1-Benzylpiperidine-4-carbonitrile (cas: 62718-31-4) 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 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.SDS of cas: 62718-31-4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

4-Phenyl-2-chinuclidinol was written by Bochow, Herbert;Schneider, Woldemar. And the article was included in Chemische Berichte in 1975.Formula: C12H15NO3S This article mentions the following:

The quinuclidinol I (R = OH) was prepared by tosylating 4-piperidinone, treating N-tosyl-4-piperidinone with NCCH2CO2Et and PhMgBr, hydrolyzing II [R1 = tosyl, R2 = CH(CN)CO2Et], hydrolyzing, reesterifying II (R1 = H, R2 = CH2CO2H), and reducing II (R1 = H, R2 = CH2CO2Et) with LiAlH4. I (R = OH) underwent chlorination to I (R = Cl), which was methoxylated or reduced to I (R = OMe, H). Oxidation of I (R = OH) occurred with ring cleavage to II (R1 = H, R2 = CH2CHO). In the experiment, the researchers used many compounds, for example, 1-Tosylpiperidin-4-one (cas: 33439-27-9Formula: 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. 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.Formula: C12H15NO3S

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Sequential C-O decarboxylative vinylation/C-H arylation of cyclic oxalates via a nickel-catalyzed multicomponent radical cascade was written by Li, Huan;Guo, Lei;Feng, Xiaoliang;Huo, Liping;Zhu, Shengqing;Chu, Lingling. And the article was included in Chemical Science in 2020.Application of 406235-30-1 This article mentions the following:

A selective, sequential C-O decarboxylative vinylation/C-H arylation of cyclic oxalate derivatives enabled by visible-light photoredox/nickel dual catalysis was described. This protocol utilizes a multicomponent radical cascade process, i.e. decarboxylative vinylation/1,5-HAT/aryl cross-coupling, to achieve efficient, site-selective dual-functionalization of saturated cyclic hydrocarbons in one single operation. This synergistic protocol provided straightforward access to sp³-enriched scaffolds such as I [R = OPh, OAc, OBz, etc.; R¹ = 4-CNC₆H₄, 4-MeC₆H₄, 2-pyridyl, etc.; X = CH₂, O; Y = CH₂, O, S, N-Boc, etc.] and an alternative retrosynthetic disconnection to diversely functionalized saturated ring systems from the simple starting materials. In the experiment, the researchers used many compounds, for example, 1-Boc-4-Hydroxy-4-methylpiperidine (cas: 406235-30-1Application of 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 are being utilized in different ways as anticancer, antiviral, antimalarial, antimicrobial, antifungal, antihypertension, analgesic, anti-inflammatory, anti-Alzheimer, antipsychotic and/or anticoagulant agents.Application of 406235-30-1

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Synthesis of Aminoethyl-Substituted Piperidine Derivatives as σ₁ Receptor Ligands with Antiproliferative Properties was written by Holtschulte, Catharina;Borgel, Frederik;Westphalinger, Stefanie;Schepmann, Dirk;Civenni, Gianluca;Laurini, Erik;Marson, Domenico;Catapano, Carlo V.;Pricl, Sabrina;Wuensch, Bernhard. And the article was included in ChemMedChem in 2022.SDS of cas: 33439-27-9 This article mentions the following:

A series of novel σ₁ receptor ligands with a 4-(2-aminoethyl)piperidine scaffold I [ R¹ = H,methyl, ethyl; R² = benzylamino, cyclohexylmethylamino etc] were prepared and biol. evaluated. The underlying concept of project were the improvement of the lipophilic ligand efficiency of previously synthesized potent σ₁ ligands. The key steps of the synthesis comprise the conjugate addition of phenylboronic acid at dihydropyridin-4(1H)-ones, homologation of the ketones and introduction of diverse amino moieties and piperidine N-substituents. 1-Methylpiperidines showed particular high σ₁ receptor affinity and selectivity over the σ₂ subtype, while piperidines with a proton, a tosyl moiety or an Et moiety exhibited considerably lower σ₁ affinity. Mol. dynamics simulations with per-residue binding free energy deconvolution demonstrated that different interactions of the basic piperidine-N-atom and its substituents (or the cyclohexane ring) with the lipophilic binding pocket consisting of Leu105, Thr181, Leu182, Ala185, Leu186, Thr202 and Tyr206 were responsible for the different σ₁ receptor affinities. Recorded logD_7.4 and calculated clogP values of I [ R¹ = H,methyl; R² = benzylamino] indicated low lipophilicity and thus high lipophilic ligand efficiency. Piperidine I [ R¹ = H; R² = benzylamino] inhibited the growth of human non-small cell lung cancer cells A427 to a similar extent as the σ₁ antagonist haloperidol. 1-Methylpiperidines I [ R¹ = methyl; R² = cyclohexylmethylamino, benzyl(methyl)amino, 4-phenylpiperazin-1-yl] showed stronger antiproliferative effects on androgen neg. human prostate cancer cells DU145 than the σ₁ ligands NE100 and S1RA. In the experiment, the researchers used many compounds, for example, 1-Tosylpiperidin-4-one (cas: 33439-27-9SDS of cas: 33439-27-9).

1-Tosylpiperidin-4-one (cas: 33439-27-9) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.SDS of cas: 33439-27-9

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem