876-08-4Relevant articles and documents
Synthesis and anti-rheumatoid arthritis activities of 3-(4-aminophenyl)-coumarin derivatives
Miao, Yuhang,Yang, Jie,Yun, Yinling,Sun, Jie,Wang, Xiaojing
, p. 450 - 461 (2021/02/19)
Rheumatoid arthritis is a chronic systemic disease characterised by an unknown aetiology of inflammatory synovitis. A large number of studies have shown that synoviocytes show tumour-like dysplasia in the pathological process of RA, and the changes in the expression of related cytokines are closely related to the pathogenesis of RA. In this thesis, a series of novel 3-(4-aminophenyl) coumarins containing different substituents were synthesised to find new coumarin anti-inflammatory drugs for the treatment of rheumatoid arthritis. The results of preliminary activity screening showed that compound 5e had the strongest inhibitory activity on the proliferation of fibroid synovial cells, and it also had inhibitory effect on RA-related cytokines IL-1, IL-6, and TNF-α. The preliminary mechanism study showed that compound 5e could inhibit the activation of NF-κB and MAPKs signal pathway. The anti-inflammatory activity of compound 5ein?vivo was further determined in the rat joint inflammation model.
Natural-product-inspired design and synthesis of two series of compounds active against Trypanosoma cruzi: Insights into structure–activity relationship, toxicity, and mechanism of action
Grand, Lucie,Popowycz, Florence,Schenkel, Eloir Paulo,Steindel, Mario,da Rosa, Rafael,Campos Bernardes, Lílian Sibelle,Dambrós, Bibiana Paula,H?ehr de Moraes, Milene,Jacolot, Ma?wenn
, (2021/11/30)
Chemical scaffolds of natural products have historically been sources of inspiration for the development of novel molecules of biological relevance, including hit and lead compounds. To identify new compounds active against Trypanosoma cruzi, we designed and synthesized 46 synthetic derivatives based on the structure of two classes of natural products: tetrahydrofuran lignans (Series 1) and oxazole alkaloids (Series 2). Compounds were screened in vitro using a cellular model of T. cruzi infection. In the first series of compounds, 11 derivatives of hit compound 5 (EC50 = 1.1 μM) were found to be active; the most potent (7, 8, and 13) had EC50 values of 5.1–34.2 μM. In the second series, 17 analogs were found active at 50 μM; the most potent compounds (47, 49, 59, and 63) showed EC50 values of 24.2–49.1 μM. Active compounds were assessed for selectivity, hemocompatibility, synergistic potential, effects on mitochondrial membrane potential, and inhibitory effect on trypanothione reductase. All active compounds showed low toxicity against uninfected THP-1 cells and human erythrocytes. The potency of compounds 5 and 8 increased steadily in combination with benznidazole, indicating a synergistic effect. Furthermore, compounds 8, 47, 49, 59, and 63 inhibited parasitic mitochondria in a dose-dependent manner. Although increased reactive oxygen species levels might lead to mitochondrial effects, the results indicate that the mechanism of action of the compounds is not dependent on trypanothione reductase inhibition. In silico calculation of chemical descriptors and principal component analysis showed that the active compounds share common chemical features with other trypanocidal molecules and are predicted to have a good ADMET profile. Overall, the results suggest that the compounds are important candidates to be further studied for their potential against T. cruzi.
ANTI-BLUE LIGHT COMPOUND, PREPARATION METHOD AND APPLICATION THEREOF
-
Paragraph 0135; 0138, (2021/07/30)
Disclosed is a blue light absorbing compound, its preparation method and use. The compound has high stability and is suitable for high temperature processing conditions as well as outdoor application. A method of covalently bonding a blue light absorbing compound with an ultraviolet light absorbing compound for increasing its stability is also provided. The compound is capable of absorbing or blocking ultraviolet light (UVA, UVB) and blue light to protect eyes. But long-wavelength blue light can be absorbed diminishingly, so that the transmitted light has a particularly good visual experience.
Preparation method of 4-formylbenzoic acid
-
Paragraph 0058; 0060; 0063; 0065; 0067; 0069, (2020/11/23)
The invention provides a preparation method of 4-formylbenzoic acid, and the method comprises the following steps: by using 4-methylbenzoyl chloride as a raw material, performing chlorinating to obtain 4-chloromethylbenzoyl chloride, performing hydrolyzing to obtain 4-chloromethyl benzoic acid, and reacting with urotropine to obtain 4-formylbenzoic acid. The method provided by the invention is simple in process, does not need special equipment and is relatively low in cost; moreover, the method provided by the invention is relatively high in product yield and purity, and large-scale industrialproduction is easy to realize. The result of the embodiment shows that the yield of each step of the preparation method of the 4-formylbenzoic acid provided by the invention is greater than or equalto 90%, and the purity of the finally obtained 4-formylbenzoic acid is greater than or equal to 99.7%.
Synthesis method of imatinib and imatinib mesylate
-
Paragraph 0092-0095, (2020/05/02)
The invention relates to a synthesis method of imatinib and imatinib mesylate. The method comprises the following steps: condensing 3-acetylpyridine and N,N-dimethylformamide dimethyl acetal which aretaken as initial raw materials to obtain 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one, then reacting with 2-methyl-5-nitrophenylguanidine nitrate to form a pyrimidine ring, performing nitro reductionto obtain N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine, amidating the N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine and 4-(chloromethyl)benzoyl chloride, performing affinitysubstitution with 1-methylpiperazine to obtain imatinib, and salifying the imatinib and methanesulfonic acid. The products obtained by the method have the advantages of few impurities, simplicity in post-treatment, high total yield, greenness, environmental protection and safety, and is suitable for a production process for large-scale industrial production of imatinib mesylate.
Synthetic method of procarbazide hydrochloride intermediate
-
Paragraph 0060-0062; 0066; 0067, (2020/05/14)
The invention discloses a synthetic method of a procarbazide hydrochloride intermediate. The preparation method comprises the following step: in a solvent, in the presence of a hydrolysis agent, carrying out hydrolysis reaction as shown in the specification on a compound as shown in a formula II to obtain a compound as shown in a formula I. The preparation method disclosed by the invention has theadvantages of high yield, high purity and stable process, and is suitable for industrial production.
Base-promoted Lewis acid catalyzed synthesis of quinazoline derivatives
Cui, Xin-Feng,Hu, Fang-Peng,Huang, Guo-Sheng,Lu, Guo-Qiang
supporting information, p. 4376 - 4380 (2020/10/20)
A one-pot protocol has been developed for the synthesis of quinazolinones from amide-oxazolines with TsCl via a cyclic 1,3-azaoxonium intermediate and 6π electron cyclization in the presence of a Lewis acid and base. The process is operationally simple and has a broad substrate scope. This method provides a unique strategy for the construction of quinazolinones.
Novel polycyclic compound
-
Paragraph 0262; 0267-0268, (2020/07/06)
The invention provides a novel polycyclic compound as well as a synthesis method and application thereof. The compound of the present invention includes a plurality of carbocyclic and/or heterocyclicstructures having visible or fluorescent light emitting groups and covalently bonded to at least one ultraviolet and/or visible (blue) light absorbing group to provide stability. The compound providedby the invention can be used as a light conversion agent, a dye, a pigment, a fluorescent agent and an ultraviolet light or blue light absorbent, and can be applied to optical films, agricultural films, optical discs (disks), optical lenses, goggles, skin care, cosmetics, illumination, coatings, adhesives, light stabilizers, panels and other products.
Palladium-catalyzed Mizoroki-Heck reactions in water using thermoresponsive polymer micelles
Suzuki, Noriyuki,Takabe, Taiga,Yamauchi, Yoshiko,Koyama, Shun,Koike, Rina,Rikukawa, Masahiro,Liao, Wei-Ting,Peng, Wen-Sheng,Tsai, Fu-Yu
, p. 1351 - 1358 (2019/02/06)
Palladium-catalyzed Mizoroki-Heck reactions were carried out in water using thermoresponsive polymer micelles. The micelles were generated from thermoresponsive block copolymers consisting of a poly(N-isopropylacrylamide) (PNIPAAm) segment and a hydrophilic segment such as nonionic poly(ethylene glycol) (PEG) (2) and anionic poly(sodium p-styrenesulfonate) (PSSNa) (9). These copolymers exhibited lower critical solution temperature (LCST) behavior at ca. 40–50 °C and showed thermal stimuli-induced formation and dissociation of micelles. The copolymers formed micelles in aqueous solution at higher temperature, where catalytic reactions proceeded. At lower temperature, the micelles dissociated to form a clear solution, enabling efficient extraction of the products from aqueous reaction mixture. In the presence of these copolymers, palladium complexes catalyzed the coupling reactions between aryl iodides and alkene compounds inside the hydrophobic micelle cores in water under relatively milder conditions. Extraction of the products from the aqueous solution of 2 or 9 was found to be efficient enough in comparison with conventional surfactants.
Synthesis and biological evaluation of 3–(4-aminophenyl)-coumarin derivatives as potential anti-Alzheimer’s disease agents
Hu, Yu-Heng,Yang, Jie,Zhang, Yun,Liu, Ke-Chun,Liu, Teng,Sun, Jie,Wang, Xiao-Jing
, p. 1083 - 1092 (2019/06/06)
The work is focused on the design of drugs that prevent and treat Alzheimer’s disease (AD) and its complications. A series of 3–(4-aminophenyl)-coumarin derivatives designed, synthesised, fully characterised and evaluated in vitro/vivo. The biological assay experiments showed that some compounds displayed a clearly selective inhibition for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among all compounds, compound 4m exhibited the highest AChE inhibition with an IC50 value of 0.091 ± 0.011 μM and compound 4k exhibited the highest BuChE inhibition with an IC50 value of 0.559 ± 0.017 μM. A zebrafish behaviour analyser (Zebrobox) was used to determine the behavioural effects of the active compound on the movement distance of the aluminium chloride-induced zebrafish. Compound 4m offered a potential drug design concept for the development of therapeutic or preventive agents for AD and its complications.
