Several 2-alkyl-5-methoxytryptamine analogues were designed and prepared as potential 5-HT(6) serotonin agonists. It was found that 5-HT(6) receptors accommodate small alkyl substituents at the indole 2-position and that the resulting compounds can bind with affinities comparable to that of serotonin. In particular, 2-ethyl-5-methoxy-N, N-dimethyltryptamine (8) binds with high affinity at human 5-HT(6) receptors (K(i) = 16 nM) relative to 5-HT (K(i) = 75 nM) and was a full agonist, at least as potent (8: K(act) = 3.6 nM) as serotonin (K(act) = 5.0 nM), in activating adenylate cyclase. Compound 8 displays modest affinity for several other populations of 5-HT receptors, notably h5-HT(1A) (K(i) = 170 nM), h5-HT(1D) (K(i) = 290 nM), and h5-HT(7) (K(i) = 300 nM) receptors, but is otherwise quite selective. Compound 8 represents the first and most selective 5-HT(6) agonist reported to date. Replacing the 2-ethyl substituent with a phenyl group results in a compound that retains 5-HT(6) receptor affinity (i.e., 10: K(i) = 20 nM) but lacks agonist character. 2-Substituted tryptamines, then, might allow entry to a novel class of 5-HT(6) agonists and antagonists.
The inhibitory effects of some flavonoids on the infectivity of rotavirus, which predominantly causes sporadic diarrhea in infants and young children, were investigated. Among tested flavonoids, diosmin and hesperidin had the most potent inhibitory activity on rotavirus infection. The fifty percent inhibitory concentration of both compounds was 10 microM. However, their aglycones did not have the inhibitory activity. The rutinose moiety of flavonoids should protect against the invasion of rotavirus into cells.
Several 2-alkyl-5-methoxytryptamine analogues are prepared and screened as serotonin agonists. In particular, derivative (IX) binds with high affinity at human 5-HT 6 receptors and is a full agonist, at least as potent as serotonin, in activating adenylate cyclase. Replacing the 2-ethyl substituent with a phenyl group results in a compound that retain 5-HT 6 receptor affinity but lacks agonist character. -(GLENNON, RICHARD A.; LEE, MASE; RANGISETTY, JAGADEESH B.; DUKAT, MALGORZATA;
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