286441-66-5Relevant academic research and scientific papers
Optimization of chromone-2-carboxamide melanin concentrating hormone receptor 1 antagonists: Assessment of potency, efficacy, and cardiovascular safety
Lynch, John K.,Freeman, Jennifer C.,Judd, Andrew S.,Iyengar, Rajesh,Mulhern, Mathew,Zhao, Gang,Napier, James J.,Wodka, Dariusz,Brodjian, Sevan,Dayton, Brian D.,Falls, Doug,Ogiela, Christopher,Reilly, Regina M.,Campbell, Thomas J.,Polakowski, James S.,Hernandez, Lisa,Marsh, Kennan C.,Shapiro, Robin,Knourek-Segel, Victoria,Droz, Brian,Bush, Eugene,Brune, Michael,Preusser, Lee C.,Fryer, Ryan M.,Reinhart, Glenn A.,Houseman, Kathryn,Diaz, Gilbert,Mikhail, Ann,Limberis, James T.,Sham, Hing L.,Collins, Christine A.,Kym, Philip R.
, p. 6569 - 6584 (2007/10/03)
Evaluation of multiple structurally distinct series of melanin concentrating hormone receptor 1 antagonists in an anesthetized rat cardiovascualar assay led to the identification of a chromone-2-carboxamide series as having excellent safety against the chosen cardiovascular endpoints at high drug concentrations in the plasma and brain. Optimization of this series led to considerable improvements in affinity, functional potency, and pharmacokinetic profile. This led to the identification of a 7-fluorochromone-2-carboxamide (22) that was orally efficacious in a diet-induced obese mouse model, retained a favorable cardiovascular profile in rat, and demonstrated dramatic improvement in effects on mean arterial pressure in our dog cardiovascular model compared to other series reported by our group. However, this analogue also led to prolongation of the QT interval in the dog that was linked to affinity for hERG channel and unexpectedly potent functional blockade of this ion channel.
Synthesis and antifungal activities of R-102557 and related dioxane- triazole derivatives
Oida, Sadao,Tajima, Yawara,Konosu, Toshiyuki,Nakamura, Yoshie,Somada, Atsushi,Tanaka, Teruo,Habuki, Shinobu,Harasaki, Tamako,Kamai, Yasuki,Fukuoka, Takashi,Ohya, Satoshi,Yasuda, Hiroshi
, p. 694 - 707 (2007/10/03)
Novel triazole compounds with a dioxane ring were synthesized. Condensation of the diol precursor 10 with various aromatic aldehydes 11 - 13 under acidic conditions afforded a series of dioxane-triazole compounds 14 - 16. The antifungal activities of the compounds 14 - 16 were evaluated in vivo in mice infection models against Candida and Aspergillus species. High activities were seen for the derivatives with one or two double bond(s) and an aromatic ring substituted with an electron-withdrawing group in the side chain. Among the derivatives, R-102557 (16R: Ar=4-(2,2,3,3- tetrafluoropropoxy)phenyl) showed excellent in vivo activities against Candida, Aspergillus and Cryptococcus species. It also showed high tolerance in a preliminary toxicity study in rats.
