- Indoles
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A 1,4-substituted cyclic amine derivative represented by the following formula or a pharmacologically acceptable salt thereof: wherein A, B, C, D, T, Y, and Z each represent a methine or a nitrogen linkage; R1, R2, R3, R4, and R5 each represent a substituent; n represents 0 or an integer of 1 to 3; m represents 0 or an integer of 1 to 6; and p represents an integer of 1 to 3. The compounds have serotonin antagonism. They are therefore clinically useful as medicaments, in particular, for treating, ameliorating, and preventing spastic paralysis. They are also useful as central muscle relaxants for ameliorating myotonia.
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- Orally bioavailable, indole-based nonpeptide GnRH receptor antagonists with high potency and functional activity
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Stereospecific introduction of a methyl group to the indole-3-side chain enhanced activity in our tryptamine-derived series of GnRH receptor antagonists. Further improvements were achieved by variation of the bicyclic amino moiety of the tertiary amide and by adjustment of the tether length to a pyridine or pyridone terminus. These modifications culminated in analogue 24, which had oral activity in a rat model and acceptable oral bioavailability and half-life in dogs and monkeys.
- Ashton, Wallace T.,Sisco, Rosemary M.,Kieczykowski, Gerard R.,Yang, Yi Tien,Yudkovitz, Joel B.,Cui, Jisong,Mount, George R.,Ren, Rena Ning,Wu, Tsuei-Ju,Shen, Xiaolan,Lyons, Kathryn A.,Mao, An-Hua,Carlin, Josephine R.,Karanam, Bindhu V.,Vincent, Stella H.,Cheng, Kang,Goulet, Mark T.
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p. 2597 - 2602
(2007/10/03)
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