INTRODUCTION/OBJECTIVE:Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) exert their pharmacological effects by inhibiting Cyclooxygenase (COX) enzymes and are widely used in the treatment of inflammation. The new potential anti-inflammatory agents of indolebased oxadiazole derivatives were developed. METHODS:A structure-activity relationship study of 62 indomethacin derivatives was designed, synthesized, and tested for COX-2 inhibition and anti-inflammatory activity in vitro. The structures were confirmed by 1H-NMR, 13C-NMR, and ESI-MS. Drug-likeness and pharmacokinetic properties were predicted by PreADME. Molecular docking was conducted to explore the binding interactions of these compounds with COX-2. RESULTS:Compounds 4a and 4f exhibited superior COX-2 inhibitory activity compared to indomethacin and celecoxib at a concentration of 500 nM. Compounds 4a and 4f (0.0001-1 μM) showed no cytotoxicity while inhibiting COX-2 in the Raw264.7 cell line. Molecular docking results indicated that compounds 4a and 4f have affinity and interaction with COX-2. CONCLUSION:Compounds 4a and 4f show selective COX-2 inhibition as potent antiinflammatory agents for the treatment of inflammatory diseases. Molecular docking studies have shown high affinity for COX-2, and the pharmacokinetic properties suggest that 4f can be categorized as a drug-like compound. Compounds 4a and 4f can be considered for further investigation.

A variety of enynals and dihydrobenzo[f]isoquinolines were effectively synthesized with favorable functional group compatibility via deoxyalkynylation of enaminones enabled by the cooperative action of Tf2O/Pd/Cu. The reaction system demonstrated the ability to be expanded to the deoxyarylation/deoxyaryloxylation of enaminones with arylboronic acids or phenols, facilitating the efficient formation of C-C/C-O bonds and showcasing the practicality and versatility of the methodology.

A cost-effective, highly regioselective and metal-free version for the synthesis of indolizine derivatives by means of Tf2O-mediated cascade reaction of pyridyl-enaminones and thiophenols/thioalcohols under mild reaction conditions has been reported. Diverse electron-rich indolizine derivatives could be obtained in up to 94% yield via the selective 1,4-addition of vinyl iminium triflate tandem cyclization/aromatization, which allowed the simultaneous construction of C-N and C-S/and one example of C-Se bonds.

C14H10O4Se2, triclinic, P (1) over bar (no. 2), a = 6.6836(11) angstrom, b = 8.9933(11) angstrom, c = 11.5062(19) angstrom, alpha = 77.128(12)degrees, beta = 87.684(14)degrees, gamma= 89.975(12)degrees, V = 673.65(18) angstrom(3), Z = 2, R-gt( F) = 0.0564, wR(ref)(F-2) = 0.1512, T = 293K.

A novel and metal catalyst-free synthesis of aryloxyacetamides from the corresponding arylboronic acids and 2-bromoacetonitrile promoted by alkaline solutions of hydrogen peroxide has been developed involving an oxidation-reduction of eco-friendly H2O2 with simultaneous reaction ipso-hydroxylation of arylboronic acid and hydration of the nitrile. This protocol is compatible with sensitive substituents attached to the arylboronic acid and provides desired products in moderate to good yields in pure water.

A highly efficient and regioselective method for constructing functionalized conjugated enals via the Tf2O-mediated tandem reaction of enaminones with thiophenols has been described. Chain products with excellent stereoselectivity could be obtained through substrate regulation. Additionally, a feasible method for synthesizing β-naphthalaldehydes through PhSO2Na/DABCO promoting hydrogen atom transfer process has also been reported here. Mechanism studies have shown that 2-formyl vinyl triflate 8 and sulfonylated enal 9 were the key intermediates in this process.

C18H13FN2O2, orthorhombic, Pbca (no. 61), a = 13.8082(4) Å, b = 9.7555(3) Å, c = 21.8116(7) Å, V = 2938.15(16) Å3, Z = 8, Rgt(F) = 0.0402, wRref(F2) = 0.1131, T = 293 K.

为发现具有抗肿瘤活性的新化合物,设计合成了 14个未见文献报道的吲哚-3-氰基类化合物.以吲哚美辛为先导化合物,对其1,3-位进行结构改造,以2-甲基-5-甲氧基-1H-吲哚为起始原料,经3-位C-H活化氰基化、1-位酰化反应得到吲哚-3-氰基类化合物(3a-3n),其结构均经1H-NMR、13C-NMR和ESI-MS确证;以顺铂为阳性对照,选取人源性肺癌细胞(A549)和人源性乳腺癌细胞(MCF-7)对所合成的化合物采用MTT法进行初步的体外抗肿瘤活性筛选,化合物3d、3k、31、3n均存在一定抑制肿瘤细胞增殖作用,化合物31对人乳腺癌细胞(MCF-7)的抑制活性最强,其IC50值为(3.45士0.25)μmol·L-1,活性接近对照组顺铂(1.167+0.132)μmol·L-1,有进一步研究价值.

An efficient Tf 2 O‐mediated regioselective C(sp 2 )−H sulfenylation of enaminones has been described. Methyl sulfoxides are employed as sulfur sources to react with different types of enaminones under mild reaction conditions, providing a straightforward approach for the synthesis of β‐amino sulfides in up to 97% yield via one‐pot manner. Moreover, this sulfenylation proceeded smoothly with oxidant‐free and metal‐free.

An economical and efficient protocol for the direct construction of amino skipped diynes through the Cu(I)-catalyzed reaction of enaminones and terminal alkynes has been described. Different kinds of symmetrical and asymmetrical 3-amino diynes could be obtained in up to 83% yield through a one-pot reaction under mild conditions.

A new and efficient protocol for the synthesis of aryloxyacetonitriles based on arylboronic acids with 2-bromoacetonitrile has been developed using eco-friendly hydrogen peroxide as oxidant under metal-free conditions. This method is compatible with arylboronic acid attached sensitive substituent and obtains desired product in moderate to good yield.

In this study, a convenient and highly efficient catalytic system for the Suzuki-Miyaura coupling reaction was investigated under mild conditions. A combination of Pd(CH3CN)2Cl2 and pipecolinic acid showed excellent catalytic performance and afforded high turnover numbers; turnover numbers were up to 4.9 × 105 for the coupling reaction of 4-bromobenzoic acid and tetraphenylboron sodium. The catalytic system was also effective for the indexes of 4-bromobenzoic acid, and high turnover numbers were obtained.

An efficient and novel nitrating reagent has been developed for ipso-nitration of arylboronic acids. By using inexpensive and commercially available Cu(NO3)(2)/CF3COOH as nitrating reagent, various nitroarenes are produced in moderate to excellent yields (51-96%). Advantages of this procedure are the operational simplicity and no need of extra catalyst.

A series of novel benzofuran derivatives containing biaryl moiety were designed and synthesized by the Suzuki cross-coupling reactions. The reactions, performed in the presence of K2CO3, EtOH/H2O and Pd(II) complex as catalyst, gave the corresponding products in good to excellent yields. The methodology allows the facile production of heterobiaryl compounds, a unique architectural motif that is ubiquitous in medicinal chemistry.

A new and efficient [(PhCH2O)(2)P(CH3)(2)CHNCH(CH3)(2)](2)PdCl2/CuI-co-catalyzed coupling-cyclization reactions of 2-iodophenol with terminal alkynes is described. Different 2-substitued benzo[b]furan derivatives are obtained in good to excellent yields. This protocol employs a relatively low palladium(II) catalyst loading in water under air conditions.

以对乙酰基苯硼酸的自偶联反应合成4,4'-二乙酰基联苯,采用1.0 mol％水溶性PdCl2 (NH2CH2COOH)2为催化剂,1.0 mmolK2CO3为助催化剂,在i-PrOH/H20(v/v＝1∶2)混合溶剂中,空气中常温反应12 h,目标化合物分离产率达95％.催化剂和产物经简单的相分离即可得到产物,反应后处理简单,产物易于纯化.

以4-溴苯甲酰苯和三甲氧基苯基硅烷为原料,1.5 mol％的钯配合物PdCl2L2为催化剂,聚乙二醇(PEG)-400和纯水为溶剂,氢氧化钠为碱性条件,经Hiyama偶联反应在100℃反应6h可合成联苯苄唑中间体-4-苯基二苯甲酮,产率高达92.6％,粗产品经重结晶处理后,纯度高达99.3％.反应结束后,催化剂通过简单的相分离重复使用催化活性下降明显,产品收率低.反应中所使用的催化剂性质稳定,合成简单,催化效率高.该反应易于操作、产品收率好、纯度高,是一种绿色友好的合成方法.

An efficient trans-PdCl2(NH2CH2COOH)2-catalyzed direct C3-cyanation of indole C─H bonds is described. Notably, free (N─H)-indoles reacted smoothly using the procedure, and the desired product 3-cyanoindoles were obtained in good to excellent yields.

2,5-Diarylated thiophenes were synthesized via metal-free,base-free sulfur heterocyclization of 1,4-diaryl-1,3-diyne with Na2S · 9H2O in DMF at 80 ℃ with a yield of 88％～100％.The influences of electronic effect and space hindrance on the sulfur heterocyclization were investigated.The results showed that the inconspicuousness difference was observed in isolated yield while the substituents containing electron-donating or electron-withdrawing in aryl-position of reactants were used,but slightly lower yield while the reactants with steric hindrance were tested.

以苄胺和苯乙炔为底物,以水溶性(NH2 CH2 COOH)2 PdCl2为催化剂,K2CO3和AgNO3为助催化剂,在DMF中一步合成2,3,6-三苯基吡啶杂环化合物,产物经1H、13C核磁共振谱进行了表征.考察了碱,反应温度、催化剂用量、反应时间等对催化反应的影响,确定了最佳的反应条件.在最佳的反应条件下,目标化合物的收率为57％.