1706-81-6Relevant academic research and scientific papers
Diaminopyrimidines as P2X3 and P2X2/3 modulators
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Page/Page column 25, (2010/11/26)
Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein A, D, E, G, J, X, Y, Z R6, R7 and R8 are as defined herein. Also provided are methods of using the compounds for treating diseases mediated by a P2X3 and/or a P2X2/3 receptor antagonist and methods of making the compounds.
Structure-activity relationship of miltirone, an active central benzodiazepine receptor ligand isolated from Salvia miltiorrhiza bunge (Danshen)
Chang,Chui,Tan,Yang,Zhong,Lee,Sham,Wong
, p. 1675 - 1692 (2007/10/02)
Twenty one o-quinonoid-type compounds and one coumarin-type compound related to miltirone (1) have been synthesized with the aim to identify the key structural elements involved in miltirone's interaction with the central benzodiazepine receptor. On the basis of their inhibition of [3H]flunitrazepam binding to bovine cerebral cortex membranes, it is apparent that ring A of miltirone is essential for affinity. Although increasing the size of ring A from six-membered to seven- and eight-membered is well-tolerated, the introduction of polar hydroxyl groups greatly reduces binding affinity. The presence of 1,1-dimethyl groups on ring A is, however, not essential. On the other hand, the isopropyl group on ring C appears to be critical for binding as its removal decreases affinity by more than 30-fold. It can, however, be replaced with a methyl group with minimal reduction in affinity. Finally, linking ring A and B with a -CH2CH2- bridge results in analogue 89, which is 6 times more potent than miltirone at the central benzodiazepine receptor (IC50 = 0.05 μM).
