26906-01-4Relevant articles and documents
Tandem Olefin Isomerization/Cyclization Catalyzed by Complex Nickel Hydride and Br?nsted Acid
Kathe, Prasad M.,Caciuleanu, Alexandru,Berkefeld, Andreas,Fleischer, Ivana
, p. 15183 - 15196 (2020/11/30)
We disclose a nickel/Br?nsted acid-catalyzed tandem process consisting of double bond isomerization of allyl ethers and amines and subsequent intramolecular reaction with nucleophiles. The process is accomplished by [(Me3P)4NiH]N(SO2CF3)2 in the presence of triflic acid. The methodology provides rapid access to tetrahydropyran-fused indoles and other oxacyclic scaffolds under very low catalyst loadings.
Novel Hypoxia-Inducible Factor 1α (HIF-1α) Inhibitors for Angiogenesis-Related Ocular Diseases: Discovery of a Novel Scaffold via Ring-Truncation Strategy
An, Hongchan,Lee, Seungbeom,Lee, Jung Min,Jo, Dong Hyun,Kim, Joohwan,Jeong, Yoo-Seong,Heo, Mi Jeong,Cho, Chang Sik,Choi, Hoon,Seo, Ji Hae,Hwang, Seyeon,Lim, Jihye,Kim, Taewoo,Jun, Hyoung Oh,Sim, Jaehoon,Lim, Changjin,Hur, Joonseong,Ahn, Jungmin,Kim, Hyun Su,Seo, Seung-Yong,Na, Younghwa,Kim, Seok-Ho,Lee, Jeewoo,Lee, Jeeyeon,Chung, Suk-Jae,Kim, Young-Myeong,Kim, Kyu-Won,Kim, Sang Geon,Kim, Jeong Hun,Suh, Young-Ger
, p. 9266 - 9286 (2018/10/24)
Ocular diseases featuring pathologic neovascularization are the leading cause of blindness, and anti-VEGF agents have been conventionally used to treat these diseases. Recently, regulating factors upstream of VEGF, such as HIF-1α, have emerged as a desirable therapeutic approach because the use of anti-VEGF agents is currently being reconsidered due to the VEGF action as a trophic factor. Here, we report a novel scaffold discovered through the complete structure-activity relationship of ring-truncated deguelin analogs in HIF-1α inhibition. Interestingly, analog 6i possessing a 2-fluorobenzene moiety instead of a dimethoxybenzene moiety exhibited excellent HIF-1α inhibitory activity, with an IC50 value of 100 nM. In particular, the further ring-truncated analog 34f, which showed enhanced HIF-1α inhibitory activity compared to analog 2 previously reported by us, inhibited in vitro angiogenesis and effectively suppressed hypoxia-mediated retinal neovascularization. Importantly, the heteroatom-substituted benzene ring as a key structural feature of analog 34f was identified as a novel scaffold for HIF-1α inhibitors that can be used in lieu of a chromene ring.
Modular Synthesis of Diverse Natural Product-Like Macrocycles: Discovery of Hits with Antimycobacterial Activity
Dow, Mark,Marchetti, Francesco,Abrahams, Katherine A.,Vaz, Luis,Besra, Gurdyal S.,Warriner, Stuart,Nelson, Adam
supporting information, p. 7207 - 7211 (2017/05/31)
A modular synthetic approach was developed in which variation of the triplets of building blocks used enabled systematic variation of the macrocyclic scaffolds prepared. The approach was demonstrated in the synthesis of 17 diverse natural product-like macrocyclic scaffolds of varied (12–20-membered) ring size. The biological relevance of the chemical space explored was demonstrated through the discovery of a series of macrocycles with significant antimycobacterial activity.