- 5-HT3 receptor agonist, novel thiazole derivative and intermediate thereof
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A 5-HT3 receptor against containing a thiazole derivative as the effective ingredient is provided and is represented by the Formula (I): STR1 wherein the A ring is substituted or unsubstituted and represents a benzene or a heterocyclic ring with one or two heteroatoms; one of L1 or L2 represents a single bond and the other is non-existent or represents an alkylene or alkenylene group; R represents: STR2
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- Substituent variation in azabicyclic triazole- and tetrazole-based muscarinic receptor ligands
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The effect of variation of the 1-azabicyclic substituent on the novel 1,2,3-triazol-4-yl-, 1,2,4-triazol-1-yl-, tetrazol-5-yl-, and tetrazol-2-yl- based muscarinic receptor ligands has been studied, and the exo- azabicyclic[2.2.1]hept-3-yl substituent was found to give the most potent and efficacious compounds. In addition, variation of the second substituent on 1,2,4-triazol-1-yl- and tetrazol-2-yl-based muscarinic receptor ligands has yielded a series of novel compounds with high potencies and efficacies, ranging from full agonists to antagonists. Small lipophilic electron withdrawing substituents give potent but low efficacy compounds, while small polar electron donating substituents give potent and efficacious compounds. The activity of these compounds is described in terms of a model of the receptor involving lipophilic and hydrogen bonding interactions. These compounds provide muscarinic ligands with high potency and a range of efficacies suitable for testing as candidate drugs in the treatment of Alzheimer's disease.
- Jenkins,Wadsworth,Bromidge,Orlek,Wyman,Riley,Hawkins
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p. 2392 - 2406
(2007/10/02)
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