63273-48-3Relevant academic research and scientific papers
Photoactivated thiazole-based DNA-cleaving agents: Dramatic change of recognition sequence: Depending on the number of thiazole units
Ninomiya,Satoh,Sugiyama,Shinomiya,Kuroda
, p. 1825 - 1826 (1996)
By increasing the number of thiazole units in the photoactive DNA cleaving compounds, 4-(3-dimethylsulfoniopropyl- aminocarbonyl)-2-[2-(4-nitrobenzoylamino)ethyl]oligo-thiazole, from one or two to three, the specificity of their DNA cleavage was dramatically altered from 5'-AAATN-3' (N ≠ G) to 5'-GG-3'.
Catalytic remote hydrohalogenation of internal alkenes
Chen, Pinhong,Jin, Jianbo,Li, Xiang,Liu, Guosheng
, (2022/02/07)
Primary alkyl halides have broad utility as fine chemicals in organic synthesis. The direct halogenation of alkenes is one of the most efficient approaches for the synthesis of these halides. Internal alkenes, in particular mixtures of isomers from refine
Phenothiazine-Tacrine Heterodimers: Pursuing Multitarget Directed Approach in Alzheimer's Disease
Gorecki, Lukas,Uliassi, Elisa,Bartolini, Manuela,Janockova, Jana,Hrabinova, Martina,Hepnarova, Vendula,Prchal, Lukas,Muckova, Lubica,Pejchal, Jaroslav,Karasova, Jana Z.,Mezeiova, Eva,Benkova, Marketa,Kobrlova, Tereza,Soukup, Ondrej,Petralla, Sabrina,Monti, Barbara,Korabecny, Jan,Bolognesi, Maria Laura
, p. 1698 - 1715 (2021/05/10)
Since 2002, no clinical candidate against Alzheimer's disease has reached the market; hence, an effective therapy is urgently needed. We followed the so-called "multitarget directed ligand"approach and designed 36 novel tacrine-phenothiazine heterodimers which were in vitro evaluated for their anticholinesterase properties. The assessment of the structure-activity relationships of such derivatives highlighted compound 1dC as a potent and selective acetylcholinesterase inhibitor with IC50 = 8 nM and 1aA as a potent butyrylcholinesterase inhibitor with IC50 = 15 nM. Selected hybrids, namely, 1aC, 1bC, 1cC, 1dC, and 2dC, showed a significant inhibitory activity toward τ(306-336) peptide aggregation with percent inhibition ranging from 50.5 to 62.1%. Likewise, 1dC and 2dC exerted a remarkable ability to inhibit self-induced Aβ1-42 aggregation. Notwithstanding, in vitro studies displayed cytotoxicity toward HepG2 cells and cerebellar granule neurons; no pathophysiological abnormality was observed when 1dC was administered to mice at 14 mg/kg (i.p.). 1dC was also able to permeate to the CNS as shown by in vitro and in vivo models. The maximum brain concentration was close to the IC50 value for acetylcholinesterase inhibition with a relatively slow elimination half-time. 1dC showed an acceptable safety and good pharmacokinetic properties and a multifunctional biological profile.
A Carbodiimide-Mediated P-C Bond-Forming Reaction: Mild Amidoalkylation of P-Nucleophiles by Boc-Aminals
Kokkala, Paraskevi,Rajeshkumar, Thayalan,Mpakali, Anastasia,Stratikos, Efstratios,Vogiatzis, Konstantinos D.,Georgiadis, Dimitris
supporting information, p. 1726 - 1730 (2021/03/08)
The first example of a carbodiimide-mediated P-C bond-forming reaction is described. The reaction involves activation of β-carboxyethylphosphinic acids and subsequent reaction with Boc-aminals using acid-catalysis. Mechanistic experiments using 31P NMR spectroscopy and DFT calculations support the contribution of unusually reactive cyclic phosphinic/carboxylic mixed anhydrides in a reaction pathway involving ion-pair "swapping". The utility of this protocol is highlighted by the direct synthesis of Boc-protected phosphinic dipeptides, as precursors to potent Zn-aminopeptidase inhibitors.
Electrochemistry Broadens the Scope of Flavin Photocatalysis: Photoelectrocatalytic Oxidation of Unactivated Alcohols
Zhang, Wen,Carpenter, Keith L.,Lin, Song
supporting information, p. 409 - 417 (2019/11/25)
Riboflavin-derived photocatalysts have been extensively studied in the context of alcohol oxidation. However, to date, the scope of this catalytic methodology has been limited to benzyl alcohols. In this work, mechanistic understanding of flavin-catalyzed oxidation reactions, in either the absence or presence of thiourea as a cocatalyst, was obtained. The mechanistic insights enabled development of an electrochemically driven photochemical oxidation of primary and secondary aliphatic alcohols using a pair of flavin and dialkylthiourea catalysts. Electrochemistry makes it possible to avoid using O2 and an oxidant and generating H2O2 as a byproduct, both of which oxidatively degrade thiourea under the reaction conditions. This modification unlocks a new mechanistic pathway in which the oxidation of unactivated alcohols is achieved by thiyl radical mediated hydrogen-atom abstraction.
Remote trifluoromethylthiolation of alcohols under visible light
Barday, Manuel,Blieck, Remi,Ruyet, Louise,Besset, Tatiana
, (2020/04/23)
An unprecedented remote and regioselective trifluoromethylthiolation reaction of alcohols was developed. Under mild conditions, a panel of free-alcohols was selectively functionalized with TolSO2SCF3 reagent as the SCF3 source in the presence of hypervalent iodide (PIDA) under blue light irradiation. This approach offered an operationally simple tool for the construction of a challenging C(sp3)-SCF3 bond at the δ-position of an alcohol by C(sp3)-H bond functionalization. Initial mechanistic studies suggested a radical pathway.
Site-Selective 1,1-Difunctionalization of Unactivated Alkenes Enabled by Cationic Palladium Catalysis
Jeon, Jinwon,Ryu, Ho,Lee, Changseok,Cho, Dasol,Baik, Mu-Hyun,Hong, Sungwoo
supporting information, (2019/07/03)
A palladium(II)-catalyzed 1,1-difunctionalization of unactivated terminal and internal alkenes via addition of two nucleophiles was developed using a cationic palladium(II) complex. The palladacycle generated in situ as a result of a regioselective addition of a nucleophile to the alkene can readily undergo regioselective β-hydride elimination and migratory insertion with a cationic palladium catalyst. The resulting η3-π-allyl palladium(II) complex is the key intermediate that reacts with a second nucleophile to furnish the desired 1,1-difunctionalization of the alkene. Under the optimized reaction conditions, a wide range of indoles and anilines add to alkene units of 3-butenoic or 4-pentenoic acid derivatives to afford the synthetically useful γ,γ- or δ,δ-difunctionalized products with excellent regiocontrol. Furthermore, by employing internal hydroxyl or acid groups and external carbon nucleophiles, this transformation enables unsymmetric 1,1-difunctionalization to forge challenging and important oxo quaternary carbon centers. Combining experiments and DFT calculations on the mechanism of the reaction is investigated in detail.
Site-Selective 1,1-Difunctionalization of Unactivated Alkenes Enabled by Cationic Palladium Catalysis
Jeon, Jinwon,Ryu, Ho,Lee, Changseok,Cho, Dasol,Baik, Mu-Hyun,Hong, Sungwoo
supporting information, p. 10048 - 10059 (2019/07/04)
A palladium(II)-catalyzed 1,1-difunctionalization of unactivated terminal and internal alkenes via addition of two nucleophiles was developed using a cationic palladium(II) complex. The palladacycle generated in situ as a result of a regioselective addition of a nucleophile to the alkene can readily undergo regioselective β-hydride elimination and migratory insertion with a cationic palladium catalyst. The resulting η 3-π-allyl palladium(II) complex is the key intermediate that reacts with a second nucleophile to furnish the desired 1,1-difunctionalization of the alkene. Under the optimized reaction conditions, a wide range of indoles and anilines add to alkene units of 3-butenoic or 4-pentenoic acid derivatives to afford the synthetically useful γ,γ-or ?,?-difunctionalized products with excellent regiocontrol. Furthermore, by employing internal hydroxyl or acid groups and external carbon nucleophiles, this transformation enables unsymmetric 1,1-difunctionalization to forge challenging and important oxo quaternary carbon centers. Combining experiments and DFT calculations on the mechanism of the reaction is investigated in detail.
Non-imidazole histamine H3 Ligands. Part VII. Synthesis, in vitro and in vivo characterization of 5-substituted-2-thiazol-4-n-propylpiperazines
Guryn, Roman,Staszewski, Marek,Stasiak, Anna,Flores, Daniel McNaught,Fogel, Wies?awa Agnieszka,Leurs, Rob,Walczynski, Krzysztof
, (2018/02/14)
H3 receptors present on histaminergic and non-histaminergic neurons, act as autoreceptors or heteroreceptors controlling neurotransmitter release and synthesis. Previous, studies have found that the compound N-methyl-N-3-phenylalkyl-2-[2-(4-n-propylpiperazin-1-yl)-1,3-thiazol-5-yl]ethan-1 -amine (ADS-531, 2c) exhibits high in vitro potency toward H3 Guinea pig jejunal receptors, with pA2 = 8.27. To optimize the structure of the lead compound ADS-531, a series of 5-substituted-2-thiazol-4-n-propylpiperazines 3 were synthesized and subjected to in vitro pharmacological characterization; the alkyl chain between position 2 of the thiazole ring and the terminal secondary N-methylamino function was elongated from three to four methylene groups and the N-methylamino functionality was substituted by benzyl-, 2-phenylethyl-, and 3-phenyl-propyl- moieties. SAR studies on novel non-imidazole, 5-substituted-2-thiazol-4-n-propyl-piperazines 3 showed that the most active compound 3a (pA2 = 8.38), additionally possessed a weak competitive H1-antagonistic activity. Therefore, compound ADS-531, which did not exhibit any H1-antagonistic activity, was chosen for further evaluation for its affinity to the recombinant rat and human histamine H3 receptors (rH3R and hH3R, respectively). ADS-531 exhibited nanomolar affinity for both rH3R and hH3R receptors. It was also shown that, ADS-531 given subchronically to rats (s.c. 3 mg/kg, 5 days) penetrated the brain, where it affected dopamine, noradrenaline and serotonin concentration; however, it did not affect histamine concentration nor feeding behavior.
Nickel-Catalyzed C-Alkylation of Nitroalkanes with Unactivated Alkyl Iodides
Rezazadeh, Sina,Devannah, Vijayarajan,Watson, Donald A.
supporting information, p. 8110 - 8113 (2017/06/28)
Enabled by nickel catalysis, a mild and general catalytic method for C-alkylation of nitroalkanes with unactivated alkyl iodides is described. Compatible with primary, secondary, and tertiary alkyl iodides; and tolerant of a wide range of functional groups, this method allows rapid access to diverse nitroalkanes.
