Category: piperidines

Molecularly targeted therapy, from the past to the near future was written by Hosono, Naoko. And the article was included in Igaku no Ayumi in 2021.Reference of 1095173-27-5 This article mentions the following:

Mol.-targeted drugs for leukemia have made remarkable progress in recent years. As the gene mutations involved in the development of leukemia and their hierarchical structure have been clarified, the development of low-mol.-weight compounds targeting the mutant genes has also made remarkable progress and in the United States, the hedgehog inhibitor mutant isocitrate dehydrogenase Enzyme (IDH) inhibitor, approval of oral methylation inhibitors has been obtained for acute myeloid leukemia (AML), and approval in Japan is awaited. Clin. trials of promising drugs for refractory leukemia, such as TP53 reactivating drugs and cyclin-dependent kinases, are also underway. Initially, antibody drugs focused only on leukemia tumor cells, but with the success of bispecific T-cell induction (BITE) antibodies in acute lymphocytic leukemia (ALL), leukemia stem cells Development of antibody drugs targeting leukemia and antibody drugs that suppress immune tolerance and induce phagocytosis of macrophages is underway. Leukemia treatment has long been centered on cell-killing antitumor agents, but is now at a turning point with the development of science. This paper outlines the current status and prospects of the development of mol.-targeted drugs for acute leukemia, which is considered to be the hottest topic at present. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5Reference of 1095173-27-5).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) 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.Reference of 1095173-27-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Scalable Flow Electrochemical Alcohol Oxidation: Maintaining High Stereochemical Fidelity in the Synthesis of Levetiracetam was written by Zhong, Xing;Hoque, Asmaul Md;Graaf, Matthew D.;Harper, Kaid C.;Wang, Fei;Genders, J. David;Stahl, Shannon S.. And the article was included in Organic Process Research & Development in 2021.Electric Literature of C11H21N2O2 This article mentions the following:

An electrochem. flow process was developed for an alc. oxidation step in the synthesis of the generic epilepsy drug levetiracetam. A crucial metric in this process is the retention of high enantiomeric purity as the oxidation of the primary alc. to the carboxylic acid proceeds via an epimerizable aldehyde intermediate. Here, three different reactor configurations are compared: undivided batch, undivided flow, and divided flow cells. The divided flow cell accesses the highest rate, throughput, and enantiomeric fidelity among the three configurations. This approach is showcased in a 200-g scale process that retains 鈮?7% enantiomeric purity and highlights a unique advantage of flow electrolysis. In the experiment, the researchers used many compounds, for example, 4-Acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (cas: 14691-89-5Electric Literature of C11H21N2O2).

4-Acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (cas: 14691-89-5) 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.Electric Literature of C11H21N2O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Development of Kinase Inactive PD173955 Analogues for Reducing Production of A尾 Peptides was written by Sinha, Anjana;Gindinova, Katherina;Mui, Emily;Netzer, William J.;Sinha, Subhash C.. And the article was included in ACS Medicinal Chemistry Letters in 2019.Recommanded Product: 171049-35-7 This article mentions the following:

Compound 3a, DV2-103, is a kinase inactive analog of a potent Abl1/Src kinase inhibitor, PD173955, 2. Both compounds, 2 and 3a, are known to reduce production of beta amyloid (A尾) peptide in cells and animal models. We have now prepared and evaluated a series of PD-173955 analogs, several of which reduced A尾 production potently. This occurs in cells expressing human full-length amyloid precursor protein (APP) and not in cells expressing APP 尾-C terminal fragment (APP-C99), suggesting that the kinase inactive analogs strongly affect 尾-secretase (BACE1) cleavage of APP, similarly to Gleevec. A combination of the kinase inactive analogs of PD173955 with a BACE1 inhibitor (BACEi), namely BACE IV, strongly reduced A尾 levels in cells, as noted previously with Gleevec and analogs. Several potent compounds also penetrated and accumulated in mouse brain in high nanomolar to low micromolar concentration In the experiment, the researchers used many compounds, for example, tert-Butyl [4,4′-bipiperidine]-1-carboxylate (cas: 171049-35-7Recommanded Product: 171049-35-7).

tert-Butyl [4,4′-bipiperidine]-1-carboxylate (cas: 171049-35-7) 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 伪-glucosidase inhibitors. The former are analogs of DNJ with an improved 伪-glucosidase inhibitory profile than that of DNJ. Boisson et al.Recommanded Product: 171049-35-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Evaluation of the toxicity of psychoactive compounds with the battery of bioassays was written by Nalecz-Jawecki, Grzegorz;Kaza, Michal;Sawicki, Jozef. And the article was included in Fresenius Environmental Bulletin in 2008.Formula: C21H27ClN2S2 This article mentions the following:

The toxicity of 14 psychoactive pharmaceuticals: antidepressants with two modes of action and antipsychotics were evaluated with the battery of six bioassays. Spirostomum ambiguum, Brachionus calyciflorus, and Thamnocephalus platyurus were more sensitive to the tested drugs than Tetrahymena thermophila, luminescent bacteria and the duckweed. In the first three tests the 24h-LC50’s ranged from 0.3 to 4.0 mg 1^-1. In each test the toxicity data were homogenous within one order of magnitude except for the Microtox. N-demethylated derivatives norfluoxetine, desipramine, nortriptyline and norclomipramine were more toxic than the parent compounds Toxicity of the tested drugs strongly depended on the pH of water. At pH 5.5 the toxicity of the drugs in Spirotox was 2-5 folds lower than the toxicity at pH of 7.2 and 8.0. In the experiment, the researchers used many compounds, for example, Thioridazine hydrochloride (cas: 130-61-0Formula: C21H27ClN2S2).

Thioridazine hydrochloride (cas: 130-61-0) 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.Formula: C21H27ClN2S2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Rationale and design of the 2 by 2 factorial design GnG-trial: a randomized phase-III study to compare two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and to compare double-blinded intensive postremission therapy with or without glasdegib in older patients with newly diagnosed AML was written by Jaramillo, Sonia;Krisam, Johannes;Le Cornet, Lucian;Kratzmann, Markus;Baumann, Lukas;Sauer, Tim;Crysandt, Martina;Rank, Andreas;Behringer, Dirk;Teichmann, Lino;Goerner, Martin;Trappe, Ralf-Ulrich;Roellig, Christoph;Krause, Stefan;Hanoun, Maher;Hopfer, Olaf;Held, Gerhard;Buske, Sebastian;Fransecky, Lars;Kayser, Sabine;Schliemann, Christoph;Schaefer-Eckart, Kerstin;Al-Fareh, Yousef;Schubert, Joerg;Geer, Thomas;Kaufmann, Martin;Brecht, Arne;Niemann, Dirk;Kieser, Meinhard;Bornhaeuser, Martin;Platzbecker, Uwe;Serve, Hubert;Baldus, Claudia D.;Mueller-Tidow, Carsten;Schlenk, Richard F.. And the article was included in Trials in 2021.Safety of 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea This article mentions the following:

Overall survival remains poor in older patients with acute myeloid leukemia (AML) with less than 10% being alive after 5 years. In recent studies, a significant improvement in event-free, relapse-free and overall survival was shown by adding gemtuzumab ozogamicin (GO), a humanized antibody-drug conjugate directed against CD33, to intensive induction therapy once or in a sequential dosing schedule. Glasdegib, the small-mol. inhibitor of smoothened (SMO), also showed improved overall survival in patients not eligible for intensive chemotherapy when combined with low-dose cytarabine compared to low-dose cytarabine alone. These findings warrant further investigations in the phase III GnG trial. This is a randomized phase III trial with measurable residual disease (MRD) after induction therapy and event-free survival (EFS) as primary endpoints. The two research questions are addressed in a 2 by 2 factorial design. Patients age 60 years and older are upfront randomized 1:1 in one of the two induction arms: GO administered to intensive induction therapy on days 1,4, and 7 vs. GO administered once on day 1 (GO-147 vs. GO-1), and double-blinded 1:1 in one of the subsequent treatment arms glasdegib vs. placebo as adjunct to consolidation therapy and as single-agent maintenance therapy for six months. Chemotherapy backbone for induction therapy consists of standard 7 + 3 schedule with cytarabine 200 mg/m2 continuously days 1 to 7, daunorubicin 60 mg/m2 days 1, 2, and 3 and high-dose cytarabine (1 g/m2, bi-daily, days 1, 2, and 3) for consolidation therapy. Addressing two primary endpoints, MRD-negativity after induction therapy and event-free survival (EFS), 252 evaluable patients are needed to reject each of the two null hypotheses at a two-sided significance level of 2.5% with a power of at least 85%. Ethics and dissemination: Ethical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5Safety of 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) 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. 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.Safety of 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Human Retinal Organoids Provide a Suitable Tool for Toxicological Investigations: A Comprehensive Validation Using Drugs and Compounds Affecting the Retina. was written by Dorgau, Birthe;Georgiou, Maria;Chaudhary, Alexander;Moya-Molina, Marina;Collin, Joseph;Queen, Rachel;Hilgen, Gerrit;Davey, Tracey;Hewitt, Philip;Schmitt, Michael;Kustermann, Stefan;Pognan, Francois;Steel, David H;Sernagor, Evelyne;Armstrong, Lyle;Lako, Majlinda. And the article was included in Stem cells translational medicine in 2022.Application of 50-52-2 This article mentions the following:

Retinal drug toxicity screening is essential for the development of safe treatment strategies for a large number of diseases. To this end, retinal organoids derived from human pluripotent stem cells (hPSCs) provide a suitable screening platform due to their similarity to the human retina and the ease of generation in large-scale formats. In this study, two hPSC cell lines were differentiated to retinal organoids, which comprised all key retinal cell types in multiple nuclear and synaptic layers. Single-cell RNA-Seq of retinal organoids indicated the maintenance of retinal ganglion cells and development of bipolar cells: both cell types segregated into several subtypes. Ketorolac, digoxin, thioridazine, sildenafil, ethanol, and methanol were selected as key compounds to screen on retinal organoids because of their well-known retinal toxicity profile described in the literature. Exposure of the hPSC-derived retinal organoids to digoxin, thioridazine, and sildenafil resulted in photoreceptor cell death, while digoxin and thioridazine additionally affected all other cell types, including M眉ller glia cells. All drug treatments caused activation of astrocytes, indicated by dendrites sprouting into neuroepithelium. The ability to respond to light was preserved in organoids although the number of responsive retinal ganglion cells decreased after drug exposure. These data indicate similar drug effects in organoids to those reported in in vivo models and/or in humans, thus providing the first robust experimental evidence of their suitability for toxicological studies. In the experiment, the researchers used many compounds, for example, 10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine (cas: 50-52-2Application of 50-52-2).

10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine (cas: 50-52-2) 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 蔚-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Application of 50-52-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

GLI2 inhibition abrogates human leukemia stem cell dormancy was written by Sadarangani, Anil;Pineda, Gabriel;Lennon, Kathleen M.;Chun, Hye-Jung;Shih, Alice;Schairer, Annelie E.;Court, Angela C.;Goff, Daniel J.;Prashad, Sacha L.;Geron, Ifat;Wall, Russell;McPherson, John D.;Moore, Richard A.;Pu, Minya;Bao, Lei;Jackson-Fisher, Amy;Munchhof, Michael;Van Arsdale, Todd;Reya, Tannishtha;Morris, Sheldon R.;Minden, Mark D.;Messer, Karen;Mikkola, Hanna K. A.;Marra, Marco A.;Hudson, Thomas J.;Jamieson, Catriona H. M.. And the article was included in Journal of Translational Medicine in 2015.Category: piperidines This article mentions the following:

Dormant leukemia stem cells LSC promote therapeutic resistance and leukemic progression as a result of unbridled activation of stem cell gene expression programs. Thus, we hypothesized that (1) deregulation of the Hedgehog Hh stem cell self-renewal and cell cycle regulatory pathway would promote dormant human LSC generation and (2) that PF- 04449913, a clin. antagonist of the GLI2 transcriptional activator, smoothened SMO, would enhance dormant human LSC eradication. To test these postulates, whole transcriptome RNA sequencing RNA-seq, microarray, qRT-PCR, stromal co-culture, confocal fluorescence microscopic, nanoproteomic, serial transplantation and cell cycle analyses were performed on FACS purified normal, chronic phase CP chronic myeloid leukemia CML, blast crisis BC phase CML progenitors with or without PF-04449913 treatment. Notably, RNA-seq analyses revealed that Hh pathway and cell cycle regulatory gene overexpression correlated with leukemic progression. While lentivirally enforced GLI2 expression enhanced leukemic progenitor dormancy in stromal co-cultures, this was not observed with a mutant GLI2 lacking a transactivation domain, suggesting that GLI2 expression prevented cell cycle transit. Selective SMO inhibition with PF-04449913 in humanized stromal co-cultures and LSC xenografts reduced downstream GLI2 protein and cell cycle regulatory gene expression. Moreover, SMO inhibition enhanced cell cycle transit and sensitized BC LSC to tyrosine kinase inhibition in vivo at doses that spare normal HSC. In summary, while GLI2, forms part of a core HH pathway transcriptional regulatory network that promotes human myeloid leukemic progression and dormant LSC generation, selective inhibition with PF-04449913 reduces the dormant LSC burden thereby providing a strong rationale for clin. trials predicated on SMO inhibition in combination with TKIs or chemotherapeutic agents with the ultimate aim of obviating leukemic therapeutic resistance, persistence and progression. In the experiment, the researchers used many compounds, for example, 1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5Category: piperidines).

1-((2R,4R)-2-(1H-Benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (cas: 1095173-27-5) 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. 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.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Discovery of a novel bicyclic compound, DS54360155, as an orally potent analgesic without mu-opioid receptor agonist activity was written by Arita, Tsuyoshi;Asano, Masayoshi;Kubota, Kazufumi;Domon, Yuki;Machinaga, Nobuo;Shimada, Kousei. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2019.Name: (S)-tert-Butyl 3-(((benzyloxy)carbonyl)amino)piperidine-1-carboxylate This article mentions the following:

We synthesized derivatives of a natural alkaloid, conolidine I, and evaluated these derivatives in the acetic acid-induced writhing test and formalin test in ddY mice after oral administration. As a result, we identified (5S)-6-methyl-1,3,4,5,6,8-hexahydro-7H-2,5-methano[1,5]diazonino[7,8-b]indol-7-one sulfate salt, II (DS54360155), with a unique and original bicyclic skeleton, as an analgesic more potent than conolidine. Moreover, II did not exhibit mu-opioid receptor agonist activity. In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl 3-(((benzyloxy)carbonyl)amino)piperidine-1-carboxylate (cas: 1002360-09-9Name: (S)-tert-Butyl 3-(((benzyloxy)carbonyl)amino)piperidine-1-carboxylate).

(S)-tert-Butyl 3-(((benzyloxy)carbonyl)amino)piperidine-1-carboxylate (cas: 1002360-09-9) 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鈥揌 bond in an axial position, and the other in an equatorial position.Name: (S)-tert-Butyl 3-(((benzyloxy)carbonyl)amino)piperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

A combined computational and experimental investigation of the oxidative ring-opening of cyclic ethers by oxoammonium cations was written by Loman, Jacob. J.;Carnaghan, Emma R.;Hamlin, Trevor A.;Ovian, John M.;Kelly, Christopher B.;Mercadante, Michael A.;Leadbeater, Nicholas E.. And the article was included in Organic & Biomolecular Chemistry in 2016.Safety of 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate This article mentions the following:

The propensity of oxoammonium cations to facilitate the oxidative ring-opening of cyclic ethers to their corresponding distal hydroxy ketones is investigated. The reaction has been evaluated using exptl. and computational methods to gain deeper insight into trends in reactivity. In the experiment, the researchers used many compounds, for example, 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate (cas: 219543-09-6Safety of 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate).

4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate (cas: 219543-09-6) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. 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.Safety of 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Interactions between N-methyl-D-aspartate receptor antagonists and the discriminative stimulus effects of morphine in rats was written by Bespalov, Anton Y.;Beardsley, Patrick M.;Balster, Robert L.. And the article was included in Pharmacology, Biochemistry and Behavior in 1998.Recommanded Product: 119431-25-3 This article mentions the following:

N-methyl-D-aspartate (NMDA) receptor antagonists alter some pharmacol. and behavioral effects of acute and chronic opioid administration. The interactions of NMDA antagonists with the discriminative stimulus properties of morphine were studied in adult male Long-Evans rats. The rats were trained to discriminate 3.2 mg/kg of s.c. morphine from water under a 2-lever fixed-ratio 10 schedule of food reinforcement. During test sessions, i.p. injections of the non-competitive NMDA receptor antagonist dizocilpine (0.03-0.2 mg/kg), the competitive antagonists NPC-17742 (1-16 mg/kg) and SDZ 220-581 (0.1-3 mg/kg), the polyamine site antagonist eliprodil (3-17.3 mg/kg), the glycine site partial agonist (+)-HA-966 (3-56 mg/kg), and the nonselective glutamate antagonist kynurenic acid (30-150 mg/kg) were coadministered with s.c. morphine (1-3.2 mg/kg; interaction tests) or water (generalization tests). In the generalization tests, none of the compounds completely substituted for morphine. Concurrent administration of morphine and NMDA antagonists did not greatly alter the discriminative stimulus properties of morphine. Various doses of NPC-17742, SDZ 220-581, or (+)-HA-966 somewhat increased the levels of morphine-appropriate lever selection, whereas some attenuation of morphine lever selection was obtained when morphine was coadministered with eliprodil. Thus, NMDA antagonists have minimal interactions with the discriminative stimulus effects of morphine. In the experiment, the researchers used many compounds, for example, 1-(4-Chlorophenyl)-2-(4-(4-fluorobenzyl)piperidin-1-yl)ethan-1-ol (cas: 119431-25-3Recommanded Product: 119431-25-3).

1-(4-Chlorophenyl)-2-(4-(4-fluorobenzyl)piperidin-1-yl)ethan-1-ol (cas: 119431-25-3) 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 prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N鈥揌 bond in an axial position, and the other in an equatorial position.Recommanded Product: 119431-25-3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem