- Compound with AMPK agonistic activity and preparation and application of prodrug thereof
-
The invention relates to a compound with AMPK agonistic activity and a prodrug thereof, and as well as a preparation method and medical application of a prodrug thereof. The compound has the structure shown in the formula (I), and the prodrug of the compound has the structure shown in the formula (II), wherein each group and the substituent are as defined in the specification. The invention discloses a preparation method of the compound and application of the compound in prevention and treatment AMPK related diseases, and the AMPK related diseases include, but are not limited to, energy metabolism abnormality related diseases. Neurodegenerative diseases and inflammation-related diseases and the like.
- -
-
Paragraph 0229-0232; 0289-0292
(2021/10/27)
-
- Catalytic SNAr Hydroxylation and Alkoxylation of Aryl Fluorides
-
Nucleophilic aromatic substitution (SNAr) is a powerful strategy for incorporating a heteroatom into an aromatic ring by displacement of a leaving group with a nucleophile, but this method is limited to electron-deficient arenes. We have now established a reliable method for accessing phenols and phenyl alkyl ethers via catalytic SNAr reactions. The method is applicable to a broad array of electron-rich and neutral aryl fluorides, which are inert under classical SNAr conditions. Although the mechanism of SNAr reactions involving metal arene complexes is hypothesized to involve a stepwise pathway (addition followed by elimination), experimental data that support this hypothesis is still under exploration. Mechanistic studies and DFT calculations suggest either a stepwise or stepwise-like energy profile. Notably, we isolated a rhodium η5-cyclohexadienyl complex intermediate with an sp3-hybridized carbon bearing both a nucleophile and a leaving group.
- Kang, Qi-Kai,Li, Ke,Li, Yuntong,Lin, Yunzhi,Shi, Hang,Xu, Lun
-
supporting information
p. 20391 - 20399
(2021/08/13)
-
- Strongly Chemiluminescent Acridinium Esters under Neutral Conditions: Synthesis, Properties, Determination, and Theoretical Study
-
Various novel acridinium ester derivatives having phenyl and biphenyl moieties were synthesized, and their optimal chemiluminescence conditions were investigated. Several strongly chemiluminescent acridinium esters under neutral conditions were found, and then these derivatives were used to detect hydrogen peroxide and glucose. Acridinium esters having strong electron-withdrawing groups such as cyano, methoxycarbonyl, and nitro at the 4-position of the phenyl moiety in phenyl 10-methyl-10λ4-acridine-9-carboxylate trifluoromethanesulfonate salt showed strong chemiluminescence intensities. The chemiluminescence intensity of 3,4-dicyanophenyl 10-methyl-10λ4-acridine-9-carboxylate trifluoromethanesulfonate salt was approximately 100 times stronger than that of phenyl 10-methyl-10λ4-acridine-9-carboxylate trifluoromethanesulfonate salt at pH 7. The linear calibration ranges of hydrogen peroxide and glucose were 0.05-10 mM and 10-2000 μM using 3,4-(dimethoxycarbonyl)phenyl 10-methyl-10λ4-acridine-9-carboxylate trifluoromethanesulfonate salt at pH 7 and pH 7.5, respectively. The proposed chemiluminescence reaction mechanism of acridinium ester via a dioxetanone structure was evaluated via quantum chemical calculation on density functional theory. The proposed mechanism was composed of the nucleophilic addition reaction of hydroperoxide anion, dioxetanone ring formation, and nonadiabatic transition due to spin-orbit coupling around the transition state (TS) to the triplet state (T1) following the decomposition pathway. The TS which appeared in the thermal decomposition would be a rate-determining step for all three processes.
- Nakazono, Manabu,Oshikawa, Yuji,Nakamura, Mizuho,Kubota, Hidehiro,Nanbu, Shinkoh
-
p. 2450 - 2461
(2017/03/11)
-
- Solvent dependent isomerization of photochromic dithienylethenes: Synthesis, photochromism, and self-assembly
-
A series of photochromic dithienylethene incorporated with phenol (DTE1), catechol (DTE2), azophenol (DTE3) groups was synthesized and characterized by means of NMR spectroscopy, mass spectrometry and elemental analysis. The photophysical, photochromic and photoisomerization properties of molecules were studied using absorption and emission spectroscopies in different solvents. The cis-trans photoisomerizations of azophenols in DTE3 compete with photocyclization of dithienylethene, resulting in low photoconversion yields in DTE3. Thermal isomerization of cis-azophenols was found to be solvent-dependent-a fast thermal relaxation from cis- to trans-isomer in chloroform, and a slow process in THF. For example in chloroform, formation of a closed-ring dithienylethene with trans-azophenols (trans-DTE3closed) was observed upon irradiation with UV light (365 nm). On the other hand, closed-ring dithienylethene with cis-azophenols (cis-DTE3closed) was formed in THF under the same condition. After forming a complex with Fe3+ ions, DTE2 showed a red shift of 27 nm in the absorption maximum. Scanning electron microscopy (SEM) analysis revealed formation of circular nanostructures with diameters in the range of 300-600 nm from DTE2closed film. Factors such as solvent, photoisomerization, and hydrogen bonding toward the formation of such supramolecular nanostructures and morphologies are discussed.
- Sen, Choong Ping,Valiyaveettil, Suresh
-
p. 95137 - 95148
(2016/10/21)
-
- Palladium-catalyzed direct arylation of phenols with aryl iodides
-
An efficient protocol of palladium-catalyzed direct para-arylation of unfunctionalized phenols with aryl iodides under mild conditions was reported. A variety of substrates were applied in this reaction with yields up to 87%.
- Long, Rongrong,Yan, Xufei,Wu, Zhiqing,Li, Zhengkai,Xiang, Haifeng,Zhou, Xiangge
-
supporting information
p. 3571 - 3574
(2015/03/30)
-
- CYCLIC PEROXIDE OXIDATION OF AROMATIC COMPOUND PRODUCTION AND USE THEREOF
-
The present invention provides a method for converting an aromatic hydrocarbon to a phenol by providing an aromatic hydrocarbon comprising one or more aromatic C-H bonds and one or more activated C-H bonds in a solvent; adding a phthaloyl peroxide to the solvent; converting the phthaloyl peroxide to a di-radical; contacting the di-radical with the one or more aromatic C-H bonds; oxidizing selectively one of the one or more aromatic C-H bonds in preference to the one or more activated C-H bonds; adding a hydroxyl group to the one of the one or more aromatic C-H bonds to form one or more phenols; and purifying the one or more phenols.
- -
-
Page/Page column 9; 10
(2014/10/15)
-
- A novel p-terphenyl derivative inducing cell-cycle arrest and apoptosis in MDA-MB-435 cells through topoisomerase inhibition
-
A novel series of p-terphenyl derivatives (1-4, 1a-4a) was successfully synthesized and their in vitro anticancer activities were evaluated. Compound 1, showing the best antiproliferative activity with IC50 1 μM against MDA-MB-435 cells, was further investigated. Compound 1 brought about a remarkable accumulation of MDA-MB-435 cells in G2/M phase prior to the induction of apoptosis. Further antitumor mechanism study indicated that compound 1, which inhibited the enzyme activity of Topo I and Topo IIα by interfering predominantly with the enzyme, could be topoisomerase suppressors instead of poisons. We conclude that compound 1 represents a novel class of Topo catalytic suppressors for developing new chemotherapeutic agents.
- Qiu, Jin,Zhao, Baobing,Shen, Yan,Chen, Wang,Ma, Yudao,Shen, Yuemao
-
p. 192 - 202
(2013/10/01)
-
- Metal-free oxidation of aromatic carbon-hydrogen bonds through a reverse-rebound mechanism
-
Methods for carbon-hydrogen (C-H) bond oxidation have a fundamental role in synthetic organic chemistry, providing functionality that is required in the final target molecule or facilitating subsequent chemical transformations. Several approaches to oxidizing aliphatic C-H bonds have been described, drastically simplifying the synthesis of complex molecules. However, the selective oxidation of aromatic C-H bonds under mild conditions, especially in the context of substituted arenes with diverse functional groups, remains a challenge. The direct hydroxylation of arenes was initially achieved through the use of strong Bronsted or Lewis acids to mediate electrophilic aromatic substitution reactions with super-stoichiometric equivalents of oxidants, significantly limiting the scope of the reaction. Because the products of these reactions are more reactive than the starting materials, over-oxidation is frequently a competitive process. Transition-metal-catalysed C-H oxidation of arenes with or without directing groups has been developed, improving on the acid-mediated process; however, precious metals are required. Here we demonstrate that phthaloyl peroxide functions as a selective oxidant for the transformation of arenes to phenols under mild conditions. Although the reaction proceeds through a radical mechanism, aromatic C-H bonds are selectively oxidized in preference to activated-H bonds. Notably, a wide array of functional groups are compatible with this reaction, and this method is therefore well suited for late-stage transformations of advanced synthetic intermediates. Quantum mechanical calculations indicate that this transformation proceeds through a novel addition-abstraction mechanism, a kind of 'reverse-rebound' mechanism as distinct from the common oxygen-rebound mechanism observed for metal-oxo oxidants. These calculations also identify the origins of the experimentally observed aryl selectivity.
- Yuan, Changxia,Liang, Yong,Hernandez, Taylor,Berriochoa, Adrian,Houk, Kendall N.,Siegel, Dionicio
-
p. 192 - 196
(2013/08/23)
-
- Modulation of spectrokinetic properties of o-quinonoid reactive intermediates by electronic factors: Time-resolved laser flash and steady-state photolysis investigations of photochromic 6- and 7-arylchromenes
-
A ready synthetic accessibility of a series of 6- and 7-arylchromenes via Pd0-catalyzed Suzuki coupling protocol has permitted a comprehensive investigation of the thermal decay behavior of a broad set of photogenerated o-quinonoid reactive intermediates. It is shown that substantial mesomeric effect between the benzopyran nucleus and the aryl ring at C6 or C7 position of the former renders significant absorption beyond 350 nm such that they are readily photoactivated to yield colored o-quinonoid intermediates. The absorption spectra of the latter are found to be strongly influenced by the substituents on C2-, C6- and C7-aryl rings; indeed the colored absorptions can be conveniently tuned by appropriate choice of substituents. The thermal decay (bleaching phenomenon), which is important from the point of view of their application in ophthalmic lenses, was investigated in each case by μs-ms as well as real-time absorption spec-troscopy. By careful experimentation, we have extracted the decay rate constants for Z,E and E,E o-quinonoid isomers of all 6- and 7-arylchromenes in an attempt to establish a correlation between the electronic attributes with their thermokinetic behavior. From a combined analysis of μs-ms (laser flash) and real-time kinetic data, it is shown that the colored o-quinonoid intermediates decay faster when the C2-aryl and C6-/C7-aryl rings contain electron-donating and electron-accepting groups, respectively. In the same vein, the decay was found to occur slowly for the reversed scenario, while intermediate decay rates are observed when both substituents are electron-donating. Thus, any substituent on the C2-aryl ring that contributes mesomerically to the development of charge on the quinonoid oxygen, and any substituent on the C6-/C7-aryl ring that exerts -I effect appear to expedite thermal decay. Furthermore, evidence is obtained for the first time from μs time-resolved laser-flash spectroscopy for the formation and characterization of the trans,cis (E,Z) o-quinonoid isomer, which has heretofore eluded spectral characterization in the photochromic phenomena of pyrans.
- Moorthy, Jarugu Narasimha,Koner, Apurba L.,Samanta, Subhas,Roy, Ankur,Nau, Werner M.
-
supporting information; experimental part
p. 4289 - 4300
(2009/12/07)
-
- Syntheses and photophysical properties of some 4-arylpyridinium salts
-
A number of 4-arylpyridines, many methoxy substituted, were prepared by an efficient two-step method involving aryl Grignard addition to 1-methyl-4-piperidone and direct aromatization of the resulting 4-aryl-4-piperidinols. The pyridines were N-alkylated to give sulfonate salts desired for their fluorescent properties. Study of selected compounds as laser dyes revealed several structures to be efficient dyes lasing in the 530-550 nm range. Two new diazaquaterphenyls were prepared and were quaternized. These salts exhibited intense fluorescence in the 420-450 nm range, but would not lase. A phenolic azaterphenyl suitably substituted for excited state intramolecular proton transfer (ESIPT) did not fluoresce at all.
- Kelley,Ansu,Budisusetyo,Ghiorghis,Qin,Kauffman
-
-
- Synthesis and property of liquid crystalline 4-alkoxyl-4″-cyano-p-terphenyls
-
The synthesis of some new 4-alkoxyl-4″-cyano-p-terphenyls is described. The preliminary characterization by means of polarized optical microscopy, differential scanning calorimetry and X-ray diffraction shows that all these compounds are thermotropically liquid-crystalline and can form both the nematic and smectic mesophases.
- Zang, Zhi-Qian,Zhang, Dong,Wan, Xin-Hua,Zhou, Qi-Feng
-
p. 145 - 158
(2007/10/03)
-
- Mesomorphic Properties of n-Alkyl-4'-n-Pentanoyloxy-Biphenyl-4-Carboxylates
-
Esters in the homologous series n-alkyl-4'-n-pentanoyloxy-biphenyl-4-carboxylates (n4COOBC, n=1-12) have been synthesized.Mesomorphic properties and phase transitions have been determined using polarizing hot-stage microscopy, DSC and x-ray.Phase transitions from SA-SB crystal and hexatic (tentatively) have been observed.The relationship between the incidence of hexatic phase and molecular structure has been discussed.
- Surendranath, V.,Fishel, D. L.,Vries, A de,Mahmood, R.,Johnson, D. L.
-
-
- Liquid crystal materials and devices
-
A novel liquid crystal material contains a compound having a molecular structure such that the material exhibits a liquid crystal phase, the molecular structure of the compound being SPC1 Or an orthosubstituted derivative thereof, where X and Y are different parasubstituents of the kind which promote liquid crystal behaviour, where the para substituent is a group selected from the following list; an alkyl group, an acyloxy group, an unsaturated group or an alkoxy group having more than one carbon atom; and where the para-substituent Y is a group selected from the following list; a cyano group, a nitro group, a group which includes a terminal cyano group, a group which includes a terminal nitro group and an acyloxy group. The material may be the said compound or it may be a multi-component solution or mixture containing it. The liquid crystal material may be nematic, smectic or cholesteric depending on the selection of the substituents X and Y. A device such as a twisted nematic effect device, incorporating the material may be operated at low temperatures. The material does not suffer from significant chemical and/or photochemical decomposition when used in a liquid crystal device.
- -
-
-