Published in Henry Rzepa's Blog

Derek Lowe has a recent post entitled " Another Funny-Looking Structure Comes Through ". He cites a recent medchem article[cite]10.1021/acsmedchemlett.5b00398[/cite] in which the following acetal sub-structure appears in a promising drug candidate (blue component below). His point is that orally taken drugs have to survive acid (green below) encountered in the stomach, and acetals are famously sensitive to hydrolysis (red below). But if

References

Organic ChemistryDrug DiscoveryBiochemistry

Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pKa Polar Moiety

Published in ACS Medicinal Chemistry Letters
Authors Chudi O. Ndubaku, James J. Crawford, Joy Drobnick, Ignacio Aliagas, David Campbell, Ping Dong, Laura M. Dornan, Sergio Duron, Jennifer Epler, Lewis Gazzard, Christopher E. Heise, Klaus P. Hoeflich, Diana Jakubiak, Hank La, Wendy Lee, Baiwei Lin, Joseph P. Lyssikatos, Jasna Maksimoska, Ronen Marmorstein, Lesley J. Murray, Thomas O’Brien, Angela Oh, Sreemathy Ramaswamy, Weiru Wang, Xianrui Zhao, Yu Zhong, Elizabeth Blackwood, Joachim Rudolph
InChI=1S/C4H11NO2.C2H3O2.Cl.H2O/c1-7-3-4(5)2-6;1-2(3)4;;/h4,6H,1-3H2,5H3;1H3;;1H2/t4-;;;/m0.../s1PEWGYHILMGIKGN-WJXVXWFNSA-N

C 6 H 16 Cl 1 N 1 O 5

Published
Authors Henry S Rzepa, Imperial College London, Imperial College London, Henry S Rzepa

# freq wb97xd/6-311g(d,p) scrf=(cpcm,solvent=water) geom=connectivity