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| Formula | C16H18N2O3 |
| Molar mass | 286.331 g·mol−1 |
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Cromakalim (INN) is apotassium channel-openingvasodilator. The activeisomer islevcromakalim. It acts onATP-sensitive potassium channels and so causes membranehyperpolarization. It can be used to treat hypertension as it will relax vascular smooth muscle to lower blood pressure. Hyperpolarisation of smooth muscle cell membranes pulls their membrane potential away from the threshold, so making it more difficult to excite them and thereby cause relaxation.
Reaction of4-cyanophenol[5] (4-Hydroxybenzonitrile) with 2-hydroxy-2-methyl-3-butyne underPTC probably proceeds to initial formation of a propargyl carbocation. The course of the reaction can be envisaged by assuming that this then attacks the aromatic ring; the resulting allylic cation can then capture the adjacent phenol oxygen and thus form the observed product (3). Treatment of that product with aqueousNBS leads to the addition of the elements ofhypobromous acid and formation of thebromohydrin (4) as a mixture of thetrans enantiomers. This cyclizes to the epoxide5 in the presence of sodium hydroxide (5). Ring opening of the oxirane with ammonia gives a mixture of thetrans amino alcohols (6). These are probably resolved at this stage and the 3S,4R-enantiomer used in the next stage. That isomer is next acylated with4-Chlorobutyryl chloride[6] to give the chloroamide (7). The anion from reaction of the amide withsodium hydride then displaces the chlorine on the end of the chain to form the pyrrolidine ring. There is thus obtained levcromakalim (8).
