70125-67-6Relevant articles and documents
Development of Orally Efficacious Allosteric Inhibitors of TNFα via Fragment-Based Drug Design
Dietrich, Justin D.,Longenecker, Kenton L.,Wilson, Noel S.,Goess, Christian,Panchal, Sanjay C.,Swann, Steven L.,Petros, Andrew M.,Hobson, Adrian D.,Ihle, David,Song, Danying,Richardson, Paul,Comess, Kenneth M.,Cox, Philip B.,Dombrowski, Amanda,Sarris, Kathy,Donnelly-Roberts, Diana L.,Duignan, David B.,Gomtsyan, Arthur,Jung, Paul,Krueger, A. Chris,Mathieu, Suzanne,McClure, Andrea,Stoll, Vincent S.,Wetter, Jill,Mankovich, John A.,Hajduk, Philip J.,Vasudevan, Anil,Stoffel, Robert H.,Sun, Chaohong
, p. 417 - 429 (2021)
Tumor necrosis factor α (TNFα) is a soluble cytokine that is directly involved in systemic inflammation through the regulation of the intracellular NF-κB and MAPK signaling pathways. The development of biologic drugs that inhibit TNFα has led to improved clinical outcomes for patients with rheumatoid arthritis and other chronic autoimmune diseases; however, TNFα has proven to be difficult to drug with small molecules. Herein, we present a two-phase, fragment-based drug discovery (FBDD) effort in which we first identified isoquinoline fragments that disrupt TNFα ligand-receptor binding through an allosteric desymmetrization mechanism as observed in high-resolution crystal structures. The second phase of discovery focused on the de novo design and optimization of fragments with improved binding efficiency and drug-like properties. The 3-indolinone-based lead presented here displays oral, in vivo efficacy in a mouse glucose-6-phosphate isomerase (GPI)-induced paw swelling model comparable to that seen with a TNFα antibody.
One-Pot Tandem Photoredox and Cross-Coupling Catalysis with a Single Palladium Carbodicarbene Complex
Hsu, Yu-Cheng,Wang, Vincent C.-C.,Au-Yeung, Ka-Chun,Tsai, Chung-Yu,Chang, Chun-Chi,Lin, Bo-Chao,Chan, Yi-Tsu,Hsu, Chao-Ping,Yap, Glenn P. A.,Jurca, Titel,Ong, Tiow-Gan
supporting information, p. 4622 - 4626 (2018/03/21)
The combination of conventional transition-metal-catalyzed coupling (2 e? process) and photoredox catalysis (1 e? process) has emerged as a powerful approach to catalyze difficult cross-coupling reactions under mild reaction conditions. Reported is a palladium carbodicarbene (CDC) complex that mediates both a Suzuki–Miyaura coupling and photoredox catalysis for C?N bond formation upon visible-light irradiation. These two catalytic pathways can be combined to promote both conventional transition-metal-catalyzed coupling and photoredox catalysis to mediate C?H arylation under ambient conditions with a single catalyst in an efficient one-pot process.
Versatile and Efficient Synthesis of Aryl-1,2,3,4-tetrahydroisoquinolines: Nickel(II) Phosphine Ligand Catalyzed Coupling of Arylmagnesium Halides to Haloisoquinolines
Pridgen, Lendon N.
, p. 1289 - 1291 (2007/10/02)
Dichloronickel(II) (dppp) was used as catalyst to prepare some previously unreported arylisoquinolines 3, which were in turn hydrogenated to aryl-1,2,3,4-tetrahydroisoquinolines 2.This procedure is the most direct and ef
