《Discovery of a Gut-Restricted JAK Inhibitor for the Treatment of Inflammatory Bowel Disease》 was written by Leonard, Kristi A.; Madge, Lisa A.; Krawczuk, Paul J.; Wang, Aihua; Kreutter, Kevin D.; Bacani, Genesis M.; Chai, Wenying; Smith, Russell C.; Tichenor, Mark S.; Harris, Michael C.; Malaviya, Ravi; Seierstad, Mark; Johnson, Marguerite E.; Venable, Jennifer D.; Kim, Suzie; Hirst, Gavin C.; Mathur, Ashok S.; Rao, Tadimeti S.; Edwards, James P.; Rizzolio, Michele C.; Koudriakova, Tatiana. Reference of trans-4-Aminocyclohexanol And the article was included in Journal of Medicinal Chemistry in 2020. The article conveys some information:
To identify Janus kinase (JAK) inhibitors that selectively target gastrointestinal tissues with limited systemic exposures, a class of imidazopyrrolopyridines with a range of phys. properties was prepared and evaluated. We identified compounds with low intrinsic permeability and determined a correlation between permeability and physicochem. properties, clogP and tPSA, for a subset of compounds This low intrinsic permeability translated into compounds displaying high colonic exposure and low systemic exposure after oral dosing at 25 mg/kg in mouse. In a mouse PK/PD model, oral dosing of lead compound 2 demonstrated dose-dependent inhibition of pSTAT phosphorylation in colonic explants post-oral dose but low systemic exposure and no measurable systemic pharmacodynamic activity. We thus demonstrate the utility of JAK inhibitors with low intrinsic permeability as a feasible approach to develop gut-restricted, pharmacol. active mols. with a potential advantage over systemically available compounds that are limited by systemic on-target adverse events. The results came from multiple reactions, including the reaction of trans-4-Aminocyclohexanol(cas: 27489-62-9Reference of trans-4-Aminocyclohexanol)
trans-4-Aminocyclohexanol(cas: 27489-62-9) belongs to anime. Milder oxidation, using reagents such as NaOCl, can remove four hydrogen atoms from primary amines of the type RCH2NH2 to form nitriles (R―C≡N), and oxidation with reagents such as MnO2 can remove two hydrogen atoms from secondary amines (R2CH―NHR′) to form imines (R2C=NR′). Tertiary amines can be oxidized to enamines (R2C=CHNR2) by a variety of reagents.Reference of trans-4-Aminocyclohexanol
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