76477-26-4Relevant articles and documents
Identification of potent and selective hydantoin inhibitors of aggrecanase-1 and aggrecanase-2 that are efficacious in both chemical and surgical models of osteoarthritis
Durham, Timothy B.,Klimkowski, Valentine J.,Rito, Christopher J.,Marimuthu, Jothirajah,Toth, James L.,Liu, Chin,Durbin, Jim D.,Stout, Stephanie L.,Adams, Lisa,Swearingen, Craig,Lin, Chaohua,Chambers, Mark G.,Thirunavukkarasu, Kannan,Wiley, Michael R.
, p. 10476 - 10485 (2014)
A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5 are zinc metalloproteases commonly referred to as aggrecanase-1 and aggrecanase-2, respectively. These enzymes are involved in the degradation of aggrecan, a key component of cartilage. Inhibitors of these enzymes could be potential osteoarthritis (OA) therapies. A series of hydantoin inhibitors of ADAMTS-4 and ADAMTS-5 were identified from a screening campaign and optimized through structure-based drug design to give hydantoin 13. Hydantoin 13 had excellent selectivity over other zinc metalloproteases such as TACE, MMP2, MMP3, MMP13, and MMP14. The compound also produced efficacy in both a chemically induced and surgical model of OA in rats.
α-Nitrosostyrenes as Three-Atom Units for the (3+1) Cyclization Reaction: Facile Access to 2,3-Dihydrodiazete N-Oxides and Their Diversified Synthetic Conversions
Shen, Li-Wen,Wang, Zhen-Hua,You, Yong,Yuan, Wei-Cheng,Zhao, Jian-Qiang,Zhou, Ming-Qiang
, p. 1094 - 1099 (2022/02/10)
An unprecedented (3+1) cyclization of α-nitrosostyrenes, generated in situ from α-bromooximes, and N-tosyloxycarbamates was developed, which enables the synthesis of a range of structurally unique and hitherto unexplored 2,3-dihydrodiazete N-oxides in mod
Improving the metabolic stability of antifungal compounds based on a scaffold hopping strategy: Design, synthesis, and structure-activity relationship studies of dihydrooxazole derivatives
Cheng, Maosheng,Su, Xin,Sun, Nannan,Sun, Yin,Tian, Linfeng,Yin, Wenbo,Zhang, Chu,Zhao, Dongmei,Zhao, Liyu,Zhao, Shizhen,Zheng, Yang
, (2021/08/07)
L-amino alcohol derivatives exhibited high antifungal activity, but the metabolic stability of human liver microsomes in vitro was poor, and the half-life of optimal compound 5 was less than 5 min. To improve the metabolic properties of the compounds, the scaffold hopping strategy was adopted and a series of antifungal compounds with a dihydrooxazole scaffold was designed and synthesized. Compounds A33-A38 substituted with 4-phenyl group on dihydrooxazole ring exhibited excellent antifungal activities against C. albicans, C. tropicalis and C. krusei, with MIC values in the range of 0.03–0.25 μg/mL. In addition, the metabolic stability of compounds A33 and A34 in human liver microsomes in vitro was improved significantly, with the half-life greater than 145 min and the half-life of 59.1 min, respectively. Moreover, pharmacokinetic studies in SD rats showed that A33 exhibited favourable pharmacokinetic properties, with a bioavailability of 77.69%, and half-life (intravenous administration) of 9.35 h, indicating that A33 is worthy of further study.
Design, synthesis and evaluation of novel 5-phenylthiophene derivatives as potent fungicidal of Candida albicans and antifungal reagents of fluconazole-resistant fungi
Cheng, Maosheng,Cui, Hengxian,Jiang, Hong,Li, Song,Liu, Lei,Su, Xin,Sun, Yin,Wu, Tianxiao,Yin, Wenbo,Zhang, Yuxin,Zhao, Dongmei,Zhao, Liyu,Zheng, Yang
, (2021/08/13)
A series of 5-phenylthiophene derivatives with novel structures were designed and synthesized to combat the increasing incidence of susceptible and drug-resistant fungal infections. The antifungal activity of the synthesized compounds was assessed against seven susceptible strains and six fluconazole-resistant strains. It is especially encouraging that compounds 17b and 17f displayed significant antifungal activities against all tested strains. Furthermore, the potent compounds 17b and 17f could prevent the formation of fungi biofilms and 17f displayed satisfactory fungicidal activity. Preliminary mechanistic studies showed that the potent antifungal activity of compound 17f stemmed from inhibition of C. albicans CYP51. In addition, Compounds 17b and 17f were almost nontoxic to mammalian A549, MCF-7, and THLE-2 cells. These results strongly suggested that compounds 17b and 17f are promising as novel antifungal drugs.
Copper-catalyzed borylative aminomethylation of C-C double and triple bonds withN,O-acetal
Qiu, Xianfan,Xu, Liugen,Wang, Shuxia,Dai, Ying,Feng, Yunqiu,Gong, Chang,Tao, Chuanzhou
, p. 3279 - 3282 (2021/04/07)
A copper-catalyzed borylaminomethylation of multiple carbon-carbon bonds withN,O-acetal and bis(pinacolato)diboron has been disclosed that offers efficient and expedient access to γ-amino boronates. The products contain a valuable amine and boronate, whic
Self-assembly of oxidation-responsive polyethylene glycol-paclitaxel prodrug for cancer chemotherapy
Dong, Chengyuan,Liu, Fusheng,Shen, Youqing,Xiang, Jiajia,Zhou, Quan,Zhou, Zhuxian
, p. 529 - 539 (2020/03/04)
Amphiphilic drug conjugates can self-assemble into nanovehicles for cancer drug delivery, but the key is to design stable yet intracellular labile drug linkers for drug retention during blood circulation but fast intracellular drug release. The conjugatio
Pd-Catalyzed Decarboxylative Olefination: Stereoselective Synthesis of Polysubstituted Butadienes and Macrocyclic P-glycoprotein Inhibitors
Chen, Xiangyang,Hao, Jiping,Houk, K. N.,Li, Yingzi,Lou, Liguang,Quan, Haitian,Song, Bichao,Wang, Lu,Xia, Yuanzhi,Xie, Peipei,Xu, Zhongliang,Yang, Weibo
supporting information, p. 9982 - 9992 (2020/06/27)
The efficient and stereoselective synthesis of polysubstituted butadienes, especially the multifunctional butadienes, represents a great challenge in organic synthesis. Herein, we wish to report a distinctive Pd(0) carbene-initiated decarboxylative olefination approach that enables the direct coupling of diazo esters with vinylethylene carbonates (VECs), vinyl oxazolidinones, or vinyl benzoxazinones to afford alcohol-, amine-, or aniline-containing 1,3-dienes in moderate to high yields and with excellent stereoselectivity. This protocol features operational simplicity, mild reaction conditions, a broad substrate scope, and gram-scalability. Notably, a structurally unique allylic Pd(II) intermediate was isolated and characterized. DFT calculation and control experiments demonstrated that a rare Pd(0) carbene intermediate could be involved in this reaction. Moreover, the polysubstituted butadienes as novel building blocks were unprecedentedly assembled into macrocycles, which efficiently inhibited the P-glycoprotein and dramatically reversed multidrug resistance in cancer cells by 190-fold.
Oxidative Deconstruction of Azetidinols to α-Amino Ketones
Allen, Lewis A. T.,Natho, Philipp,Parsons, Philip J.,Raclea, Robert-Cristian,White, Andrew J. P.
, p. 9375 - 9385 (2020/08/14)
A silver-mediated synthesis of α-amino ketones via the oxidative deconstruction of azetidinols has been developed using a readily scalable protocol with isolated yields up to 80percent. The azetidinols are easily synthesized in one step and can act as protecting groups for these pharmaceutically relevant synthons. Furthermore, mechanistic insights are presented and these data have revealed that the transformation is likely to proceed through the β-scission of an alkoxy radical, followed by oxidation and C-N cleavage of the resulting α-amido radical.
Probing the Effects of Heterocyclic Functionality in [(Benzene)Ru(TsDPENR)Cl] Catalysts for Asymmetric Transfer Hydrogenation
Barrios-Rivera, Jonathan,Xu, Yingjian,Wills, Martin
supporting information, p. 7223 - 7227 (2019/10/08)
A range of TsDPEN catalysts containing heterocyclic groups on the amine nitrogen atom were prepared and evaluated in the asymmetric transfer hydrogenation of ketones. Bidentate and tridentate ligands demonstrated a mutual exclusivity directly related to their function as catalysts. A broad series of ketones were reduced with these new catalysts, permitting the ready identification of an optimal catalyst for each substrate and revealing the subtle effects that changes to nearby donor groups can exhibit.
Β - azole - phenylketo derivative and use thereof (by machine translation)
-
Paragraph 0090-0095; 0097, (2019/04/06)
The invention belongs to the technical field of drug synthesis, provides such as general formula β - azole - phenylketo derivative and its stereoisomers or its pharmaceutically acceptable salt, hydrate, solvate or prodrug and their method of preparation, wherein A, B, R1 , R2 , R3 , X has the definition given in the specification. The invention of the compound provided by the superficial and deep fungus has relatively strong inhibiting activity, with the clinical use of antifungal drug compared, has high activity, low toxicity, antimicrobial spectrum and the like, can be used for preparing the antifungal drug. (by machine translation)
