Conformational and steric modifications of the pyran ring of the potassium-channel activator cromakalim

Structure-Activity Relationships of KATP Channel Openers

“…For cromakalim optimum substitution is attributed to the dimethyl group, which was shown to be superior to monomethyl and profoundly better than diethyl. The dihydro compound was virtually devoid of activity [28]. In a series of benzopyran-4-carbothioamides, however, larger substituents are advantageous: 2-methyl-2-n-propyl and the spirocyclic cyclobutyl or cyclopentyl moieties yielded the most potent derivatives (see above).…”

Effect of deuteration on the metabolism and clearance of some pharmacologically active compounds—synthesis and in vitro metabolism of deuterated derivatives of dronedadrone

“…β‐propiolactone, 9 , was also used in the synthesis of analogues 3e and 3g carrying D atoms α to the tertiary nitrogen atom. Starting from the readily available nitro‐substituted phenol, 14 , base mediated opening gave the propionic acid, 15 , which was deutero‐reduced to the intermediate alcohol, 16 , prior to activation as the tosyl derivative 17 . Reaction of 17 with the previously described deuterated amine, 5 or D9‐n‐butylamine, gave the two nitro derivatives 18e and 18g respectively.…”

Stereoselective Synthesis of cis,cis‐Configured Perhydroquinoxaline‐5‐Carbonitrile from Cyclohex‐2‐en‐1‐ol

“…Despite a broad screening of reaction conditions and in contrast to other epoxides , deprotonated pyrrolidin‐2‐one did not react with the epoxide 3 , even after addition of the Lewis acid Ti(O i ‐Pr) 4 . However, the synthesis of the diol 6 was achieved by dihydroxylation of the alkene 7 , which was prepared by deprotonation of pyrrolidin‐2‐one with NaH and subsequent reaction with 3‐bromocyclohex‐1‐ene .…”