“…However, NPS2143 has unfavorable pharmacokinetic properties in vivo (see section V.D). Later on, several HTS and lead optimization programs have yielded a number of negative allosteric CaSR modulators from various chemical classes: compounds relatively closely related to NPS2143 (Gavai et al, 2005), but also different molecules, such as Calhex 231 (compound II in Table 13) and derivatives thereof (Petrel et al, 2003;Kessler et al, 2006), trisubstituted pyridines/ pyrimidines (compound V in Table 13) (Arey et al, 2005;Yang et al, 2009), benzyloxy analogs (compound IV in Table 13) (Balan et al, 2009), 2-benzylpyrrolidinesubstituted aryloxypropanols (compound VI in Table 13) , 3H-quinazolin-4-ones (compound VII in Table 13) (Shcherbakova et al, 2005), and 4-arylquinazolin-2-ones (compound VIII in Table 13) (Widler et al, 2010) were identified as novel calcilytics, having essentially similar effects on intracellular calcium mobilization and inositol formation in cellular assay systems, some of them also being active in vivo. More compounds having in vivo activity are discussed below.…”