Category: 144230-52-4

Most of the natural products isolated at present are heterocyclic compounds, so heterocyclic compounds occupy an important position in the research of organic chemistry. A compound: 144230-52-4, is researched, SMILESS is FC1(F)CCNCC1.[H]Cl, Molecular C5H10ClF2NJournal, Article, Journal of Medicinal Chemistry called Design of Development Candidate eFT226, a First in Class Inhibitor of Eukaryotic Initiation Factor 4A RNA Helicase, Author is Ernst, Justin T.; Thompson, Peggy A.; Nilewski, Christian; Sprengeler, Paul A.; Sperry, Samuel; Packard, Garrick; Michels, Theodore; Xiang, Alan; Tran, Chinh; Wegerski, Christopher J.; Eam, Boreth; Young, Nathan P.; Fish, Sarah; Chen, Joan; Howard, Haleigh; Staunton, Jocelyn; Molter, Jolene; Clarine, Jeff; Nevarez, Andres; Chiang, Gary G.; Appleman, Jim R.; Webster, Kevin R.; Reich, Siegfried H., the main research direction is flavagline analog preparation antitumor activity lipophilicity; structure activity flavagline analog antitumor lipophilicity; Zotatifin design synthesis antitumor lipophilicity; eukaryotic initiation factor 4A RNA helicase inhibitor flavagline analog.Quality Control of 4,4-Difluoropiperidine hydrochloride.

Dysregulation of protein translation is a key driver for the pathogenesis of many cancers. Eukaryotic initiation factor 4A (eIF4A), an ATP-dependent DEAD-box RNA helicase, is a critical component of the eIF4F complex, which regulates cap-dependent protein synthesis. The flavagline class of natural products (i.e., rocaglamide A) has been shown to inhibit protein synthesis by stabilizing a translation-incompetent complex for select mRNAs (mRNAs) with eIF4A. Despite showing promising anticancer phenotypes, the development of flavagline derivatives as therapeutic agents has been hampered because of poor drug-like properties as well as synthetic complexity. A focused effort was undertaken utilizing a ligand-based design strategy to identify a chemotype with optimized physicochem. properties. Also, detailed mechanistic studies were undertaken to further elucidate mRNA sequence selectivity, key regulated target genes, and the associated antitumor phenotype. This work led to the design of eFT226 (Zotatifin), I, a compound with excellent physicochem. properties and significant antitumor activity that supports clin. development.

This compound(4,4-Difluoropiperidine hydrochloride)Quality Control of 4,4-Difluoropiperidine hydrochloride was discussed at the molecular level, the effects of temperature and reaction time on the properties of the compound were discussed, and the optimum reaction conditions were selected.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Moehle, Mark S.; Bender, Aaron M.; Dickerson, Jonathan W.; Foster, Daniel J.; Qi, Aidong; Cho, Hyekyung P.; Donsante, Yuping; Peng, Weimin; Bryant, Zoey; Stillwell, Kaylee J.; Bridges, Thomas M.; Chang, Sichen; Watson, Katherine J.; O’Neill, Jordan C.; Engers, Julie L.; Peng, Li; Rodriguez, Alice L.; Niswender, Colleen M.; Lindsley, Craig W.; Hess, Ellen J.; Conn, P. Jeffrey; Rook, Jerri M. published the article 《Discovery of the First Selective M4 Muscarinic Acetylcholine Receptor Antagonists with in Vivo Antiparkinsonian and Antidystonic Efficacy》. Keywords: muscarinic acetylcholine receptor antagonist antiparkinson antidystonic Parkinson disease.They researched the compound: 4,4-Difluoropiperidine hydrochloride( cas:144230-52-4 ).COA of Formula: C5H10ClF2N. Aromatic heterocyclic compounds can be divided into two categories: single heterocyclic and fused heterocyclic. In addition, there is a lot of other information about this compound (cas:144230-52-4) here.

Nonselective antagonists of muscarinic acetylcholine receptors (mAChRs) that broadly inhibit all five mAChR subtypes provide an efficacious treatment for some movement disorders, including Parkinson’s disease and dystonia. Despite their efficacy in these and other central nervous system disorders, antimuscarinic therapy has limited utility due to severe adverse effects that often limit their tolerability by patients. Recent advances in understanding the roles that each mAChR subtype plays in disease pathol. suggest that highly selective ligands for individual subtypes may underlie the antiparkinsonian and antidystonic efficacy observed with the use of nonselective antimuscarinic therapeutics. Our recent work has indicated that the M4 muscarinic acetylcholine receptor has several important roles in opposing aberrant neurotransmitter release, intracellular signaling pathways, and brain circuits associated with movement disorders. This raises the possibility that selective antagonists of M4 may recapitulate the efficacy of nonselective antimuscarinic therapeutics and may decrease or eliminate the adverse effects associated with these drugs. However, this has not been directly tested due to lack of selective antagonists of M4. Here, we utilize genetic mAChR knockout animals in combination with nonselective mAChR antagonists to confirm that the M4 receptor activation is required for the locomotor-stimulating and antiparkinsonian efficacy in rodent models. We also report the synthesis, discovery, and characterization of the first-in-class selective M4 antagonists VU6013720, VU6021302, and VU6021625 and confirm that these optimized compounds have antiparkinsonian and antidystonic efficacy in pharmacol. and genetic models of movement disorders.

The article 《Discovery of the First Selective M4 Muscarinic Acetylcholine Receptor Antagonists with in Vivo Antiparkinsonian and Antidystonic Efficacy》 also mentions many details about this compound(144230-52-4)COA of Formula: C5H10ClF2N, you can pay attention to it, because details determine success or failure

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Product Details of 144230-52-4. The mechanism of aromatic electrophilic substitution of aromatic heterocycles is consistent with that of benzene. Compound: 4,4-Difluoropiperidine hydrochloride, is researched, Molecular C5H10ClF2N, CAS is 144230-52-4, about Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma. Author is Hansen, Joshua D.; Correa, Matthew; Nagy, Mark A.; Alexander, Matt; Plantevin, Veronique; Grant, Virginia; Whitefield, Brandon; Huang, Dehua; Kercher, Timothy; Harris, Roy; Narla, Rama Krishna; Leisten, Jim; Tang, Yang; Moghaddam, Mehran; Ebinger, Katalin; Piccotti, Joseph; Havens, Courtney G.; Cathers, Brian; Carmichael, James; Daniel, Thomas; Vessey, Rupert; Hamann, Lawrence G.; Leftheris, Katerina; Mendy, Derek; Baculi, Frans; LeBrun, Laurie A.; Khambatta, Gody; Lopez-Girona, Antonia.

Many patients with multiple myeloma (MM) initially respond to treatment with modern combination regimens including immunomodulatory agents (lenalidomide and pomalidomide) and proteasome inhibitors. However, some patients lack an initial response to therapy (i.e., are refractory), and although the mean survival of MM patients has more than doubled in recent years, most patients will eventually relapse. To address this need, we explored the potential of novel cereblon E3 ligase modulators (CELMoDs) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). We found that optimization beyond potency of degradation, including degradation efficiency and kinetics, could provide efficacy in a lenalidomide-resistant setting. Guided by both phenotypic and protein degradation data, we describe a series of CELMoDs for the treatment of RRMM, culminating in the discovery of CC-92480, a novel protein degrader and the first CELMoD to enter clin. development that was specifically designed for efficient and rapid protein degradation kinetics.

After consulting a lot of data, we found that this compound(144230-52-4)Product Details of 144230-52-4 can be used in many types of reactions. And in most cases, this compound has more advantages.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Recommanded Product: 4,4-Difluoropiperidine hydrochloride. So far, in addition to halogen atoms, other non-metallic atoms can become part of the aromatic heterocycle, and the target ring system is still aromatic. Compound: 4,4-Difluoropiperidine hydrochloride, is researched, Molecular C5H10ClF2N, CAS is 144230-52-4, about Discovery of M-808 as a Highly Potent, Covalent, Small-Molecule Inhibitor of the Menin-MLL Interaction with Strong In Vivo Antitumor Activity.

Targeting the menin-MLL protein-protein interaction is a new therapeutic strategy for the treatment of acute leukemia carrying MLL fusion (MLL leukemia). We describe herein the structure-based optimization of a class of covalent menin inhibitors, which led to the discovery of M-808 (16)(I) as a highly potent and efficacious covalent menin inhibitor. M-808 effectively inhibits leukemia cell growth at low nanomolar concentrations and is capable of achieving partial tumor regression in an MV4;11 xenograft tumor model in mice at a well-tolerated dose schedule. Determination of the co-crystal structure of M-808 in complex with menin provides a structural basis for their high-affinity, covalent interactions. M-808 represents a promising, covalent menin inhibitor for further optimization and evaluation toward developing a new therapy for the treatment of MLL leukemia.

This literature about this compound(144230-52-4)Recommanded Product: 4,4-Difluoropiperidine hydrochloridehas given us a lot of inspiration, and I hope that the research on this compound(4,4-Difluoropiperidine hydrochloride) can be further advanced. Maybe we can get more compounds in a similar way.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Rescourio, Gwenaella; Gonzalez, Ana Z.; Jabri, Salman; Belmontes, Brian; Moody, Gordon; Whittington, Doug; Huang, Xin; Caenepeel, Sean; Cardozo, Mario; Cheng, Alan C.; Chow, David; Dou, Hannah; Jones, Adrie; Kelly, Ron C.; Li, Yihong; Lizarzaburu, Mike; Lo, Mei-Chu; Mallari, Rommel; Meleza, Cesar; Rew, Yosup; Simonovich, Scott; Sun, Daqing; Turcotte, Simon; Yan, Xuelei; Wong, Simon G.; Yanez, Evelyn; Zancanella, Manuel; Houze, Jonathan; Medina, Julio C.; Hughes, Paul E.; Brown, Sean P. published an article about the compound: 4,4-Difluoropiperidine hydrochloride( cas:144230-52-4,SMILESS:FC1(F)CCNCC1.[H]Cl ).Electric Literature of C5H10ClF2N. Aromatic heterocyclic compounds can be classified according to the number of heteroatoms or the size of the ring. The authors also want to convey more information about this compound (cas:144230-52-4) through the article.

Overexpression of the antiapoptotic protein Mcl-1 provides a survival advantage to some cancer cells, making inhibition of this protein an attractive therapeutic target for the treatment of certain types of tumors. Herein, we report our efforts toward the identification of a novel series of macrocyclic Mcl-1 inhibitors featuring an α-hydroxy phenylacetic acid pharmacophore or bioisostere. This work led to the discovery of 1(I), a potent Mcl-1 inhibitor (IC50 = 19 nM in an OPM-2 cell viability assay) with good pharmacokinetic properties and excellent in vivo efficacy in an OPM-2 multiple myeloma xenograft model.

There are many compounds similar to this compound(144230-52-4)Electric Literature of C5H10ClF2N. if you want to know more, you can check out my other articles. I hope it will help you，maybe you’ll find some useful information.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In organic chemistry, atoms other than carbon and hydrogen are generally referred to as heteroatoms. The most common heteroatoms are nitrogen, oxygen and sulfur. Now I present to you an article called Aminations and arylations by direct C-O activation for the design of 7,8-dihydro-6H-5,8-ethanopyrido[3,2-d]pyrimidines, published in 2021, which mentions a compound: 144230-52-4, mainly applied to arylboronic acid dihydroethanopyridopyrimidinone palladium RuPhos catalyst Suzuki cross coupling; amine dihydroethanopyridopyrimidinone palladium xantphos catalyst Buchwald Hartwig cross coupling; dihydroethanopyridopyrimidinone amine PyBroP activator nucleophilic aromatic substitution; dihydroethanopyridopyrimidinamine preparation, Related Products of 144230-52-4.

The design of some novel disubstituted 7,8-dihydro-6H-5,8-ethanopyrido[3,2-d]pyrimidine derivatives was reported. The series was developed from quinuclidinone, which afforded versatile platforms bearing one lactam function in position C-2 that were then used to create C-N or C-C bonds for SNAr or palladium-catalyzed cross-coupling reactions by in situ C-O activation. The reaction conditions were optimized under microwave irradiation and a wide range of amines or boronic acids were used to determine the scope and limitations of each method. To complete this study, the X-ray crystallog. data of 4-Phenyl-2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-6H-5,8-ethanopyrido[3,2-d]pyrimidine were used to formally establish the structures of the products.

Compound(144230-52-4)Related Products of 144230-52-4 received a lot of attention, and I have introduced some compounds in other articles, similar to this compound(4,4-Difluoropiperidine hydrochloride), if you are interested, you can check out my other related articles.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Synthetic Route of C5H10ClF2N. The protonation of heteroatoms in aromatic heterocycles can be divided into two categories: lone pairs of electrons are in the aromatic ring conjugated system; and lone pairs of electrons do not participate. Compound: 4,4-Difluoropiperidine hydrochloride, is researched, Molecular C5H10ClF2N, CAS is 144230-52-4, about Identification of 2,4-Disubstituted Imidazopyridines as Hemozoin Formation Inhibitors with Fast-Killing Kinetics and In Vivo Efficacy in the Plasmodium falciparum NSG Mouse Model. Author is Horatscheck, Andre; Andrijevic, Ana; Nchinda, Aloysius T.; Le Manach, Claire; Paquet, Tanya; Khonde, Lutete Peguy; Dam, Jean; Pawar, Kailash; Taylor, Dale; Lawrence, Nina; Brunschwig, Christel; Gibhard, Liezl; Njoroge, Mathew; Reader, Janette; van der Watt, Mariette; Wicht, Kathryn; de Sousa, Ana Carolina C.; Okombo, John; Maepa, Keletso; Egan, Timothy J.; Birkholtz, Lyn-Marie; Basarab, Gregory S.; Wittlin, Sergio; Fish, Paul V.; Street, Leslie J.; Duffy, James; Chibale, Kelly.

A series of 2,4-disubstituted imidazopyridines, originating from a SoftFocus Kinase library, was identified from a high throughput phenotypic screen against the human malaria parasite Plasmodium falciparum. Hit compounds showed moderate asexual blood stage activity. During lead optimization, several issues were flagged such as cross-resistance against the multidrug-resistant K1 strain, in vitro cytotoxicity, and cardiotoxicity and were addressed through structure-activity and structure-property relationship studies. Pharmacokinetic properties were assessed in mice for compounds showing desirable in vitro activity, a selectivity window over cytotoxicity, and microsomal metabolic stability. Frontrunner compound 37(I) showed good exposure in mice combined with good in vitro activity against the malaria parasite, which translated into in vivo efficacy in the P. falciparum NOD-scid IL-2Rγnull (NSG) mouse model. Preliminary mechanistic studies suggest inhibition of hemozoin formation as a contributing mode of action.

Here is just a brief introduction to this compound(144230-52-4)Synthetic Route of C5H10ClF2N, more information about the compound(4,4-Difluoropiperidine hydrochloride) is in the article, you can click the link below.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

So far, in addition to halogen atoms, other non-metallic atoms can become part of the aromatic heterocycle, and the target ring system is still aromatic.Nguyen, William; Dans, Madeline G.; Ngo, Anna; Gancheva, Maria R.; Romeo, Ornella; Duffy, Sandra; de Koning-Ward, Tania F.; Lowes, Kym N.; Sabroux, Helene Jousset; Avery, Vicky M.; Wilson, Danny W.; Gilson, Paul R.; Sleebs, Brad E. researched the compound: 4,4-Difluoropiperidine hydrochloride( cas:144230-52-4 ).SDS of cas: 144230-52-4.They published the article 《Structure activity refinement of phenylsulfonyl piperazines as antimalarials that block erythrocytic invasion》 about this compound( cas:144230-52-4 ) in European Journal of Medicinal Chemistry. Keywords: phenyl sulfonyl piperazine preparation antimalarial antitumor lipophilicity SAR; Antimalarial; Erythrocyte invasion; Malaria; Phenylsulfonyl piperazine; Plasmodium. We’ll tell you more about this compound (cas:144230-52-4).

The optimization and further characterization of the phenylsulfonyl piperazine class I [R = 4-Me, 3-t-Bu, 4-Br, etc.; R1 = pyrrolidin-1-yl, piperidin-1-yl, 1,2,3,4-tetrahydroisoquinolin-2-yl, etc.; X = -(N(CH2)2N(CH2)2)-CH(CH3), -(NCH(CH3)N(CH2)2)-CH(CH3), -(NC(CH3)2N(CH2)2)-CH(CH3), etc.] was described. During the optimization process the functionality required for P. falciparum asexual stage activity was defined and determined the alpha-carbonyl S-Me isomer was important for antimalarial potency. The optimized compounds I also possessed comparable activity against multidrug resistant strains of P. falciparum and displayed weak activity against sexual stage gametocytes. The optimized compounds I blocked erythrocyte invasion consistent with the asexual activity observed and therefore the phenylsulfonyl piperazine analogs described could serve as useful tools for studying Plasmodium erythrocyte invasion.

Here is just a brief introduction to this compound(144230-52-4)SDS of cas: 144230-52-4, more information about the compound(4,4-Difluoropiperidine hydrochloride) is in the article, you can click the link below.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Category: piperidines. The protonation of heteroatoms in aromatic heterocycles can be divided into two categories: lone pairs of electrons are in the aromatic ring conjugated system; and lone pairs of electrons do not participate. Compound: 4,4-Difluoropiperidine hydrochloride, is researched, Molecular C5H10ClF2N, CAS is 144230-52-4, about Discovery of CYR715: A novel carboxylic acid-containing soluble guanylate cyclase stimulator. Author is Rennie, Glen R.; Barden, Timothy C.; Bernier, Sylvie G.; Carvalho, Andrew; Deming, Renee; Germano, Peter; Hudson, Colleen; Im, G-Yoon J.; Iyengar, Rajesh R.; Jia, Lei; Jung, Joon; Kim, Elise; Lee, Thomas W.-H.; Mermerian, Ara; Moore, Joel; Nakai, Takashi; Perl, Nicholas R.; Tobin, Jenny; Zimmer, Daniel P.; Renhowe, Paul A..

Soluble guanylate cyclase (sGC) is a clin. validated therapeutic target in the treatment of pulmonary hypertension. Modulators of sGC have the potential to treat diseases that are affected by dysregulation of the NO-sGC-cGMP signal transduction pathway. This letter describes the SAR efforts that led to the discovery of CYR715, a novel carboxylic acid-containing sGC stimulator, with an improved metabolic profile relative to our previously described stimulator, IWP-051. CYR715 addressed potential idiosyncratic drug toxicity (IDT) liabilities associated with the formation of reactive, migrating acyl glucuronides (AG) found in related carboxylic acid-containing analogs and demonstrated high oral bioavailability in rat and dose-dependent hemodynamic pharmacol. in normotensive Sprague-Dawley rats.

This literature about this compound(144230-52-4)Category: piperidineshas given us a lot of inspiration, and I hope that the research on this compound(4,4-Difluoropiperidine hydrochloride) can be further advanced. Maybe we can get more compounds in a similar way.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

The chemical properties of alicyclic heterocycles are similar to those of the corresponding chain compounds. Compound: 4,4-Difluoropiperidine hydrochloride, is researched, Molecular C5H10ClF2N, CAS is 144230-52-4, about Observation of Vortex Domains in a Two-Dimensional Lead Iodide Perovskite Ferroelectric, the main research direction is lead iodide two dimensional perovskite ferroelec vortex domain.Application of 144230-52-4.

Topol. defects, such as vortices and skyrmions, provide a wealth of splendid possibilities for new nanoscale devices because of their marvelous electronic, magnetic, and mech. behaviors. Recently, great advances have been made in the study of the ferroelec. vortex in conventional perovskite oxides, such as BaTiO3 and BiFeO3. Despite extensive interest, however, no intriguing ferroelec. vortex structures have yet been found in organic-inorganic hybrid perovskites (OIHPs), which are desirable for their mech. flexibility, ease of fabrication, and low acoustical impedance. We observed the robust vortex-antivortex topol. configurations in a two-dimensional (2D) layered OIHP ferroelec. (4,4-DFPD)2PbI4 (4,4-DFPD is 4,4-difluoropiperidinium). This provides future directions for the study of perovskites and makes it a promising alternative for nanoscale ferroelec. devices in medical, micromech., and biomech. applications.

As far as I know, this compound(144230-52-4)Application of 144230-52-4 can be applied in many ways, which is helpful for the development of experiments. Therefore many people are doing relevant researches.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem