Synthesis of HNMT, NNMT intermediates and PK

NCATS is in need of custom synthesis and bioanalytical services in internal projects focused on developing small molecule inhibitors of physiological small molecule methyltransferases. NACTS is pursuing small molecules in two projects where methyltransferases are implicated in disease. NCATS requires key intermediates that will allow for the lab to scale up lead compounds or make analogs. NCATS also requires exposure data in various tissues of interest to gauge compound concentrations to select compounds for POC.

100g of N-(pyridin-3-yl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-e][1,4]diazepin-8-amine 100g of (tert-butyl (R)-3-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3- yl)piperidine-1- carboxylate. Mouse PK on at least 10 compounds with routes and tissues determined. The final purity has to be >95% with optical purity >98%. Spectroscopic characterization and analytical data will be required and verified.