Acid-base interactions in some isoquinoline and quinazoline amino derivatives

Preparation and pH-Switching of Fluorescent Borylated Arylisoquinolines for Multilevel Molecular Logic

“…8.4 for 1,4-dimethylpiperazine) and (b) the less basic isoquinoline moiety (p K a ca. 4.8 for parent isoquinoline in 1/1 methanol/water) . The nitrogen at the aryl ring could also be protonated (in fact only observed for dye 3 ; see following), giving rise to a third protonation site.…”

“…4.8 for parent isoquinoline in 1/1 methanol/ water). 54 The nitrogen at the aryl ring could also be protonated (in fact only observed for dye 3; see following), giving rise to a third protonation site. However, the latter nitrogen is evidently the least basic site because of the involvement of its lone pair in the ICT process and the electrostatic repulsion caused by the neighboring protonated lateral amino function.…”

Design of Small-Molecule Active-Site Inhibitors of the S1A Family Proteases as Procoagulant and Anticoagulant Drugs

“…Like the other fVIIa inhibitors discussed, the recently reported macrocyclic carbamate 16 (fVIIa K i = 1.4 nM, highly selective over fXa, fXIa, thrombin, and trypsin but poorly selective over PK, K i = 36 nM) also makes extensive interactions with the large S2 (and to some extend the S3) site of fVIIa (Figure f). Rather than a P1 benzamidine group, 16 contains an aminoisoquinoline, which is significantly less basic (1-aminoisoquinoline has a p K a of 7.27 ). However, permeability of macrocyclic compounds such as 16 was still observed to be low but could be improved upon further optimization − to afford derivatives of 16 with not only improved permeability and oral bioavailability (up to 40% in dog) but also selectivity over kallikreins …”