Heterocyclic Building Blocks-Benzisoxazole

Pedersen, Simon S.; Donslund, Aske S.; Mikkelsen, Jesper H.; Bakholm, Oskar S.; Papp, Florian; Jensen, Kim B.; Gustafsson, Magnus B. F.; Skrydstrup, Troels published the artcile< A Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides>, Computed Properties of 84163-77-9, the main research area is aliphatic carboxamide preparation; alkyl zinc halide methyldiphenylsilanecarboxylic acid amine thiocarbonylation nickel catalyst; aliphatic carboxamides; aminocarbonylation; isotope labeling; nickel; thioesters.

A series of pharmaceutically relevant small mols. and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon-13. Key to the success of this novel carbon isotope labeling technique is the observation that 13C-labeled Ni(II)-acyl complexes, formed from a 13CO insertion step with Ni(II)-alkyl intermediates, rapidly react in less than one minute with 2,2′-dipyridyl disulfide to quant. form the corresponding 2-pyridyl thioesters. Either the use of 13C-SilaCOgen or 13C-COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one-pot acylation of a series of structurally diverse amines provides the desired 13C-labeled carboxamides in good yields. A single electron transfer pathway is proposed between the Ni(II)-acyl complexes and the disulfide providing a reactive Ni(III)-acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chem. for carbon-11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of 13C-labeled liraglutide and insulin degludec, representing two antidiabetic drugs.

Chemistry – A European Journal published new progress about Acylation. 84163-77-9 belongs to class benzisoxazole, and the molecular formula is C12H13FN2O, Computed Properties of 84163-77-9.

Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

Krol, Marek; Slifirski, Grzegorz; Kleps, Jerzy; Ulenberg, Szymon; Belka, Mariusz; Baczek, Tomasz; Siwek, Agata; Stachowicz, Katarzyna; Szewczyk, Bernadeta; Nowak, Gabriel; Duszynska, Beata; Herold, Franciszek published the artcile< Synthesis of novel pyrido[1,2-c]pyrimidine derivatives with 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole moiety as potential SSRI and 5-HT1A receptor ligands>, Quality Control of 84163-77-9, the main research area is pyridopyrimidine piperidinyl benzisoxazole preparation hydroxytryptamine receptor serotonin transporter ligand; antidepressants; drug design; dual 5-HT1A/SERT activity; pyrido[1,2-c]pyrimidines.

Two series of novel 4-aryl-2H-pyrido[1,2-c]pyrimidines I (R = Ph, 2-MeC6H4, 4-MeOC6H4, 4-FC6H4, etc.) and 4-aryl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidines II (R as above) were synthesized. The chem. structures of the new compounds were confirmed by 1H and 13C NMR spectroscopy and ESI-HRMS spectrometry. The affinities of all compounds for the 5-HT1A receptor and serotonin transporter protein (SERT) were determined by in vitro radioligand binding assays. The test compounds demonstrated very high binding affinities for the 5-HT1A receptor of all derivatives in the both series and generally low binding affinities for the SERT protein, with the exception of compounds I (R = Ph) and II (R = 4-MeOC6H4). Extended affinity tests for the receptors D2, 5-HT2A, 5-HT6 and 5-HT7 were conducted with regard to selected compounds I (R = Ph, 2-ClC6H4) and II (R = 4-MeOC6H4, 4-FC6H4). All four compounds demonstrated very high affinities for the D2 and 5-HT2A receptors. Compounds I (R = Ph) and II (R = 4-MeOC6H4) also had high affinities for 5-HT7, while I (R = 2-ClC6H4) and II (4-FC6H4) held moderate affinities for this receptor. Compounds I (R = Ph) and II (R = 4-MeOC6H4) were also tested in vivo to identify their functional activity profiles with regard to the 5-HT1A receptor, with I (R = Ph) demonstrating the activity profile of a presynaptic agonist. Metabolic stability tests were also conducted for the compounds I (R = Ph, 2-ClC6H4).

International Journal of Molecular Sciences published new progress about 5-HT1A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 84163-77-9 belongs to class benzisoxazole, and the molecular formula is C12H13FN2O, Quality Control of 84163-77-9.

Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

Gao, Lanchang; Yang, Zhengge; Xiong, Jiaying; Hao, Chao; Ma, Ru; Liu, Xin; Liu, Bi-Feng; Jin, Jian; Zhang, Guisen; Chen, Yin published the artcile< Design, synthesis and biological investigation of flavone derivatives as potential multi-receptor atypical antipsychotics>, SDS of cas: 84163-77-9, the main research area is flavone preparation antipsychotic dopamine serotonin receptor; atypical antipsychotics; dopamine; multi-target; serotonin.

The design of a series of novel flavone derivatives I (X = N, CH; Ar = 2-methoxyphenyl, 6-fluorobenzo[d]isoxazol-3-yl, pyrimidin-2-yl, etc.; n = 1, 2), II (m = 1, 2) and III (R1 = H, Cl; R2 = H, Me) was synthesized as potential broad-spectrum antipsychotics by using multi-receptor affinity strategy between dopamine receptors and serotonin receptors. Among them, I (X = CH, Ar = 6-fluorobenzo[d]isoxazol-3-yl, n = 2), (IV) exhibited a promising preclin. profile. Compound IV not only showed high affinity for dopamine D2, D3, and serotonin 5-HT1A, 5-HT2A receptors, but was also endowed with low to moderate activities on 5-HT2C, α1, and H1 receptors, indicating a low liability to induce side effects such as weight gain, orthostatic hypotension and QT prolongation. In vivo behavioral studies suggested that compound IV has favorable effects in alleviating the schizophrenia-like symptoms without causing catalepsy. Taken together, compound V has the potential to be further developed as a novel atypical antipsychotic.

Molecules published new progress about 5-HT1A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 84163-77-9 belongs to class benzisoxazole, and the molecular formula is C12H13FN2O, SDS of cas: 84163-77-9.

Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

Kumar, Roopender; Floden, Nils J.; Whitehurst, William G.; Gaunt, Matthew J. published the artcile< A general carbonyl alkylative amination for tertiary amine synthesis>, Safety of 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole, the main research area is tertiary amine preparation carbonyl alkylative amination.

The ubiquity of tertiary alkylamines in pharmaceutical and agrochem. agents, natural products and small-mol. biol. probes has stimulated efforts towards their streamlined synthesis. Arguably the most robust method for the synthesis of tertiary alkylamines is carbonyl reductive amination, which comprises two elementary steps: the condensation of a secondary alkylamine with an aliphatic aldehyde to form an all-alkyl-iminium ion, which is subsequently reduced by a hydride reagent. Direct strategies were sought for a ‘higher order’ variant of this reaction via the coupling of an alkyl fragment with an alkyl-iminium ion that was generated in situ. However, despite extensive efforts, the successful realization of a ‘carbonyl alkylative amination’ has not yet been achieved. Here the authors present a practical and general synthesis of tertiary alkylamines through the addition of alkyl radicals to all-alkyl-iminium ions. The process is facilitated by visible light and a silane reducing agent, which trigger a distinct radical initiation step to establish a chain process. This operationally straightforward, metal-free and modular transformation forms tertiary amines, without structural constraint, via the coupling of aldehydes and secondary amines with alkyl halides. The structural and functional diversity of these readily available precursors provides a versatile and flexible strategy for the streamlined synthesis of complex tertiary amines.

Nature (London, United Kingdom) published new progress about Aliphatic aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 84163-77-9 belongs to class benzisoxazole, and the molecular formula is C12H13FN2O, Safety of 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole.

Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

Lu, Bin; Xu, Minghao; Qi, Xiaotian; Jiang, Min; Xiao, Wen-Jing; Chen, Jia-Rong published the artcile< Switchable Radical Carbonylation by Philicity Regulation>, Application In Synthesis of 84163-77-9, the main research area is amide preparation; ketoamide preparation; aryl amine cyclicbutane oxime ester carbon monoxide carbonylation photocatalyst.

A new strategy that exploits photoredox catalysis to regulate the philicity of amine coupling partners to drive switchable radical carbonylation reactions was described. In double carbonylation, amines e.g., aniline were first transformed into nitrogen radical cations by single-electron transfer-oxidation and coupled with CO to form carbamoyl radicals, which further underwent radical cross-coupling with the incipient cyanoalkyl acyl radicals to afford the double carbonylation products. Upon the addition of stoichiometric 4-dimethylaminopyridine (DMAP), DMAP competitively traps the initially formed cyanoalkyl acyl radical to form the relatively stabilized cyanoalkyl acyl-DMAP salts that engaged in the subsequent substitution with the nucleophilic amines to produce the single carbonylation products. The reaction proceeded smoothly with excellent selectivity in the presence of various amine nucleophiles at room temperature, generating valuable amides e.g., 4-cyano-N-phenylbutanamide and α-ketoamides e.g., 5-cyano-2-oxo-N-phenylpentanamide in a versatile and controlled fashion. Combined exptl. and computational studies provided mechanistic insights into the possible pathways.

Journal of the American Chemical Society published new progress about Amides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 84163-77-9 belongs to class benzisoxazole, and the molecular formula is C12H13FN2O, Application In Synthesis of 84163-77-9.

Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

Gao, Lanchang; Hao, Chao; Chen, Jiali; Ma, Ru; Zheng, Lu; Wu, Qingkun; Liu, Xin; Liu, Bi-Feng; Zhang, Guisen; Chen, Yin; Jin, Jian published the artcile< Discovery of a new class of multi-target heterocycle piperidine derivatives as potential antipsychotics with pro-cognitive effect>, Electric Literature of 84163-77-9, the main research area is benzoisoxazolyl piperidine synthesis antipsychotic procognitive; Atypical antipsychotics; Cognition; Dopamine; Multi-target; Serotonin.

A series of benzoisoxazolylpiperidine derivatives were synthesized by using the multi-target strategies and their potent affinities for dopamine (DA), serotonin (5-HT) and human histamine H3 receptors have been evaluated. Of these compounds, the promising candidate 4w (I) displayed high affinities for D2, D3, 5-HT1A, 5-HT2A and H3, a moderate affinity for 5-HT6, negligible effects on the human ether-a-go-go-related gene (hERG) channel, low affinities for off-target receptors (5-HT2C, adrenergic α1 and H1). In addition, the animal behavioral study revealed that, compared to risperidone, compound 4w significantly inhibited apomorphine-induced climbing and MK-801-induced movement behaviors with a high threshold for catalepsy and low liabilities for weight gain and hyperprolactinemia. Results from the conditioned avoidance response test and novel object recognition task demonstrated that 4w had pro-cognitive effects. Thus, the antipsychotic drug-like activities of 4w indicate that it may be a potential polypharmacol. antipsychotic candidate drug.

Bioorganic & Medicinal Chemistry Letters published new progress about 5-HT1A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (receptor affinity). 84163-77-9 belongs to class benzisoxazole, and the molecular formula is C12H13FN2O, Electric Literature of 84163-77-9.

Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

Gu, Zheng-Song; Wang, Wen-Tao; Qian, Hao; Zhou, Ai-Nan; Sun, Hong-Bin; Zhang, Qing-Wei; Li, Jian-Qi published the artcile< Synthesis and antidepressant effect of novel aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7>, Recommanded Product: 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole, the main research area is aralkyl piperazine piperidine antidepressant SSRI 5HT1A 5HT7 target; 5-HT(1A) receptor; 5-HT(7) receptor; Antidepressant; Serotonin reuptake inhibition.

A series of novel aralkyl piperazine and piperidine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the selective compound were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compound 19a (I) exhibited high affinities for the 5-HT1A/5-HT7 receptors (5-HT1A, Ki = 12 nM; 5-HT7, Ki = 3.2 nM) coupled with potent serotonin reuptake inhibition (IC50 = 14 nM) and showed a marked antidepressant-like effect in the FST and TST models.

Bioorganic & Medicinal Chemistry Letters published new progress about 5-HT reuptake inhibitors. 84163-77-9 belongs to class benzisoxazole, and the molecular formula is C12H13FN2O, Recommanded Product: 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole.

Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

He, Ze-Liang; Zhang, Yi; Chen, Zhi-Chao; Du, Wei; Chen, Ying-Chun published the artcile< Cascade Multicomponent Assemblies Involving 1,3-Enynes via Auto-Tandem Palladium Catalysis>, Product Details of C12H13FN2O, the main research area is chromene preparation chemoselective regioselective diastereoselective; enyne carbonyl organoboronic reagent nucleophile cascade multicomponent palladium catalyst; dihydroquinoline preparation chemoselective regioselective diastereoselective; benzoxepine preparation chemoselective regioselective diastereoselective; annulated indole preparation chemoselective regioselective diastereoselective.

Here, a three-component auto-tandem reaction of 1,3-enyne-tethered carbonyls 2-R4C(O)-3-R-4-R1-5-R2-6-R3C6O(CH2)nCCCH=CH2 (R = H, Me; R1 = H, t-Bu, MeO; RR1 = -CH=CH-CH=CH-; R2 = H, Cl, Me; R3 = H, Cl; R4 = H, Me; n = 1, 2), organoboronic reagents R5B(OH)2 (R5 = Et, styryl, 2-naphthyl, benzofuran-3-yl, etc.), and suitable nucleophiles R6H [R6 = morpholino, methylbenzylamino, 2-hydroxy-1-naphthyl] catalyzed by palladium, proceeding through consecutive intramol. vinylogous addition, Suzuki coupling, and allylic alkylation was reported. This process exhibited high chemo- and regioselectivity with 1,3,4-trifunctionalization of the 1,3-enyne motif, and a wide range of 2H-chromenes and benzo[b]oxepine I, 1,2-dihydroquinoline II, 1,7-annulated indole III, and other frameworks was efficiently constructed in fair to good yields and E/Z selectivity.

Organic Letters published new progress about Addition reaction (vinylogous). 84163-77-9 belongs to class benzisoxazole, and the molecular formula is C12H13FN2O, Product Details of C12H13FN2O.

Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

Marganakop, Sheetal B.; Kamble, Ravindra R.; Sannaikar, Madivalagouda S.; Bayannavar, Praveen K.; Kumar, S. Madan; Inamdar, Sanjeev R.; Shirahatti, Arunkumar M.; Desai, Saleem M.; Joshi, Shrinivas D. published the artcile< SCXRD, DFT and molecular docking based structural analyses towards novel 3-piperazin-1-yl-benzo[d]isothiazole and 3-piperidin-4-yl-benzo[d]isoxazoles appended to quinoline as pharmacological agents>, Safety of 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole, the main research area is quinoline piperazinyl benzoisothiazole benzoisoxazole preparation antibacterial antifungal DFT; bromomethyl chloroquinoline benzothiazole benzoxazole nucleophilic substitution reaction.

Novel quinoline containing 3-piperazin-1-yl-benzo[d]isothiazoles and 3-piperidin-4-yl-benzo[d]isoxazole were synthesized. Hirshfeld surface, electrostatic potential maps were obtained resp. from SCXRD and DFT studies. These compounds were analyzed for in vitro antimicrobial activity and correlated with energy difference (ΔE) between HOMO and LUMO energy levels obtained from DFT and correlated with ΔE of standard drug to explain the activity. Further the antimicrobial activity was corroborated by docking against various target enzymes. The present work provided some hints for developing novel antimicrobial quinoline derivatives

Journal of Molecular Structure published new progress about Antibacterial agents. 84163-77-9 belongs to class benzisoxazole, and the molecular formula is C12H13FN2O, Safety of 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole.

Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

Paul, Anirudra; Seidel, Daniel published the artcile< α-Functionalization of Cyclic Secondary Amines: Lewis Acid Promoted Addition of Organometallics to Transient Imines>, COA of Formula: C12H13FN2O, the main research area is cyclic secondary amine alpha functionalization Lewis acid organometallic imine.

Cyclic imines, generated in situ from their corresponding N-lithiated amines and a ketone hydride acceptor, undergo reactions with a range of organometallic nucleophiles to generate α-functionalized amines in a single operation. Activation of the transient imines by Lewis acids that are compatible with the presence of lithium alkoxides is crucial to accommodate a broad range of nucleophiles including lithium acetylides, Grignard reagents, and aryllithiums with attenuated reactivities.

Journal of the American Chemical Society published new progress about Alkali metal alkoxides, lithium alkoxides Role: RGT (Reagent), RACT (Reactant or Reagent). 84163-77-9 belongs to class benzisoxazole, and the molecular formula is C12H13FN2O, COA of Formula: C12H13FN2O.

Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics