13916-98-8Relevant academic research and scientific papers
Novel 3-oxazolidinedione-6-aryl-pyridinones as potent, selective, and orally active EP3 receptor antagonists
Jin, Jian,Morales-Ramos, Angel,Eidam, Patrick,Mecom, John,Li, Yue,Brooks, Carl,Hilfiker, Mark,Zhang, David,Wang, Ning,Shi, Dongchuan,Tseng, Pei-San,Wheless, Karen,Budzik, Brian,Evans, Karen,Jaworski, Jon-Paul,Jugus, Jack,Leon, Lisa,Wu, Charlene,Pullen, Mark,Karamshi, Bhumika,Rao, Parvathi,Ward, Emma,Laping, Nicholas,Evans, Christopher,Leach, Colin,Holt, Dennis,Su, Xin,Morrow, Dwight,Fries, Harvey,Thorneloe, Kevin,Edwards, Richard
scheme or table, p. 316 - 320 (2010/11/18)
High-throughput screening and subsequent optimization led to the discovery of novel 3-oxazolidinedione-6-aryl-pyridinones exemplified by compound 2 as potent and selective EP3 antagonists with excellent pharmacokinetic properties. Compound 2 was orally active and showed robust in vivo activities in overactive bladder models. To address potential bioactivation liabilities of compound 2, further optimization resulted in compounds 9 and 10, which maintained excellent potency, selectivity, and pharmacokinetic properties and showed no bioactivation liability in glutathione trapping studies. These highly potent, selective, and orally active EP3 antagonists are excellent tool compounds for investigating and validating potential therapeutic benefits from selectively inhibiting the EP3 receptor.
ERβ ligands. 3. Exploiting two binding orientations of the 2-phenylnaphthalene scaffold to achieve ERβ selectivity
Mewshaw, Richard E.,Edsall Jr., Richard J.,Yang, Cuijian,Manas, Eric S.,Xu, Zhang B.,Henderson, Ruth A.,Keith Jr., James C.,Harris, Heather A.
, p. 3953 - 3979 (2007/10/03)
The 2-phenylnaphthalene scaffold was explored as a simplified version of genistein in order to identify ER selective ligands. With the aid of docking studies, positions 1, 4, and 8 of the 2-phenylnaphthalene template were predicted to be the most potentially influential positions to enhance ER selectivity using two different binding orientations. Both orientations have the phenol moiety mimicking the A-ring of genistein. Several compounds predicted to adopt orientations similar to that of genistein when bound to ERβ were observed to have slightly higher ER affinity and selectivity than genistein. The second orientation we exploited, which was different from that of genistein when bound to ERβ, resulted in the discovery of several compounds that had superior ER selectivity and affinity versus genistein. X-ray structures of two ER selective compounds (i.e., 15 and 47) confirmed the alternate binding mode and suggested that substituents at positions 1 and 8 were responsible for inducing selectivity. One compound (i.e., 47, WAY-202196) was further examined and found to be effective in two models of inflammation, suggesting that targeting ER may be therapeutically useful in treating certain chronic inflammatory diseases.
Substituted phenyl naphthalenes as estrogenic agents
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, (2008/06/13)
This invention provides estrogen receptor modulators of formula I, having the structure 1wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10, are as defined in the specification, or a pharmaceutically acceptable salt thereof.
Synthesis of 5-Fluoro-7,12-dimethylbenzanthracene-3,4-dione: Nucleophilic Displacement of Fluorine in Polyaromatic Hydrocarbons
Sheikh, Younus M.,Ekwuribe, Nnochiri,Dhawan, Balram,Witiak, Donald T.
, p. 4341 - 4344 (2007/10/02)
The synthesis of 5-fluoro-7,12-dimethylbenzanthracene-3,4-dione (24) from 3-acetyl-1-fluoro-7-methoxynaphthalene (12) via 5-fluoro-3-methoxy-7,12-dimethylbenzanthracene (20) is described.Unexpectedly reaction of 20 with ethylthio anion and BBr3/CH2C
