14366-59-7Relevant academic research and scientific papers
Synthesis and SAR of 1,3-thiazolyl thiophene and pyridine derivatives as potent, orally active and S1P3-sparing S1P1 agonists
Asano, Masayoshi,Nakamura, Tsuyoshi,Sekiguchi, Yukiko,Mizuno, Yumiko,Yamaguchi, Takahiro,Tamaki, Kazuhiko,Shimozato, Takaichi,Doi-Komuro, Hiromi,Kagari, Takashi,Tomisato, Wataru,Inoue, Ryotaku,Yuita, Hiroshi,Oguchi-Oshima, Keiko,Kaneko, Reina,Nara, Futoshi,Kawase, Yumi,Masubuchi, Noriko,Nakayama, Shintaro,Koga, Tetsufumi,Namba, Eiko,Nasu, Hatsumi,Nishi, Takahide
scheme or table, p. 3083 - 3088 (2012/06/04)
We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P3-sparing S1P1 agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3. Extensive SAR studies led to the finding of 1,3-thiazole 24c with the EC50 value of 3.4 nM for human S1P1, and over 5800-fold selectivity against S1P3. In rat on host versus graft reaction (HvGR), the ID50 value of 24c was determined at 0.07 mg/kg. The pharmacokinetics in rat and monkey is also reported. Compared to compound 3, 24c showed excellent stability against enterobacteria.
The selective reaction of aryl halides with KOH: Synthesis of phenols, aromatic ethers, and benzofurans
Anderson, Kevin W.,Ikawa, Takashi,Tundel, Rachel E.,Buchwald, Stephen L.
, p. 10694 - 10695 (2007/10/03)
The direct and selective synthesis of phenols from aryl/heteroaryl halides and KOH has been achieved through the use of highly active monophosphine-based catalysts derived from Pd2dba3 and ligands L1 or L2 and the biphasic solvent system 1,4-dioxane/H2O. We have also demonstrated a one-pot method of phenol formation/alkylation for the preparation of alkyl aryl ethers from aryl halides. In many instances, this protocol overcomes limitations in existing Pd-catalyzed coupling reactions of aliphatic alcohols with aryl halides. Finally, we demonstrate that substituted benzofurans can be prepared efficiently via a Pd-catalyzed phenol formation/cyclization protocol starting from 2-chloroaryl alkynes. Copyright
