Chem. Sci. 2021, 12 (34), 11294-11305
DOI: 10.1039/d1sc03615g
Fominova K.; Diachuk T.; Granat D.; Savchuk T.; Vilchynskyi V.; Svitlychnyi O.; Meliantsev V.; Kovalchuk I.; Litskan E.; Levterov V. V.; Badlo V. R.; Vaskevych R. I.; Vaskevych A. I.; Bolbut A. V.; Semeno V. V.; Iminov R.; Shvydenko K.; Kuznetsova A. S.; Dmytriv Y. V.; Vysochyn D.; Ripenko V.; Tolmachev A. A.; Pavlova O.; Kuznietsova H.; Pishel I.; Borysko P.; Mykhailiuk P. K.
A general approach to a new generation of spirocyclic molecules - oxa-spirocycles - was developed. The key synthetic step was iodocyclization. More than 150 oxa-spirocyclic compounds were prepared. Incorporation of an oxygen atom into the spirocyclic unit dramatically improved water solubility (by up to 40 times) and lowered lipophilicity. More potent oxa-spirocyclic analogues of antihypertensive drug terazosin were synthesized and studied in vivo.