Synthesis, biological activity and conformational study of 1,4-benzoxazinederivatives as potassium channel modulators

With the aim of discovering new molecules with K+-channel activating proper ties, we have synthesized derivatives of cromakalim (CRK), an important mol ecule which shows specific affinity towards K+ channels, by replacing the b enzopyrane ring of this reference compound with a 1,4-benzoxazine moiety. A different number of substituents showing a good discrimination between hyd rophobic and electronic properties have been inserted at the 6-position of the 1,4-benzoxazine ring. We describe here the synthesis and discuss the so lid state conformation of these new molecules. When tested on rat aorta rin g precontracted with phenylephrine, two compounds (2c and 2d) showed a conc entration-dependent relaxation similar to that measured for cromakalim but less potent than this reference drug. (C) Elsevier, Paris.