Identification of 4-amino-2-cyclohexylaminoquinazolines as metabolically stable melanin-concentrating hormone receptor 1 antagonists.

The optimization of the distance between two key pharmacophore features within our first hit compounds 1a and 2a led to the identification of a new class of potent non-peptidic antagonists for the MCH-R1, based around 4-amino-2-cyclohexylaminoquinazolines. In particular, ATC0065 (2c), N2-[cis-4-([2-[4-Bromo-2-(trifluoromethoxy)phenyl]ethyl]amino)cyclohexyl]-N4,N4-dimethylquinazoline-2,4-diamine dihydrochloride, bound with high affinity to the MCH-R1 (IC50 value of 16 nM) and showed good metabolic stability in liver microsomes from human and rat.

Reduction of respiration rates by forming aggregations in diapausing adults of the shield bug, Parastrachia japonensis.

Parastrachia japonensis adults in diapause live mostly in aggregated conditions and can survive more than 1 year on only water. In this study, we demonstrated that diapausing adults had a high tendency to form clusters with no sexual bias. When 3-40 insects were enclosed in chambers of equal volume used to measure respiration, oxygen consumption was reduced to nearly half that when a single individual was enclosed.