- CYCLIC AMIDES AS METAP-2 INHIBITORS
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Compounds of the formula (I), in which R1, R3, R5, R6, R7, R, X and Y have the meanings indicated in Claim 1, are inhibitors of methionine aminopeptidase and can be employed for the treatment of tumou
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Paragraph 0396; 0397; 0398
(2015/02/19)
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- Synthesis and Structure-Activity Studies of a Series of Spirooxazolidine-2,4-diones: 4-Oxa Analogues of the Muscarinic Agonist 2-Ethyl-8-methyl-2,8-diazaspirodecane-1,3-dione
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A series of spirooxazolidine-2,4-dione derivatives related to the putative M1 agonist 2-ethyl-8-methyl-2,8-diazaspirodecane-1,3-dione (RS86; 1) were synthesized.The compounds were evaluated as cholinergic agents in in vitro binding assays and in in vivo pharmacological tests including antiamnesic effects using scopolamine-treated mice, hypothermia, and salivation in mice.Four compounds (5a,c,f and 17a) exhibited affinity for cortical M1 receptors and reversed scopolamine-induced impairment of mouse passive avoidance tasks, as did 1.Among these compounds only 5a exhibited M1-receptor stimulating activity in pithed rats.Structural requirements for muscarinic activity in this series of spirooxazolidine-2,4-dione derivatives were as strict as those reported for spirocuccinimide derivatives including 1.The antiamnesic dose of 3-ethyl-8-methyl-1-oxo-3,8-diazaspirodecane-2,4-dione (5a) was 2 orders of magnitude lower than the doses inducing hypothermia and salivation, in contrast to 1 for which the former dose was only 5-10-fold lower than the latter.These results suggest that the 8-azaspirodecane skeleton represents a useful template for designing new muscarinic agonists as antidementia drugs.
- Tsukamoto, Shin-ichi,Ichihara, Masato,Wanibuchi, Fumikazu,Usuda, Shinji,Hidaka, Kazuyuki,et al.
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p. 2292 - 2299
(2007/10/02)
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- 2-Methyl-1,3-dioxaazaspirodecanes as Novel Muscarinic Cholinergic Agonists
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Many nonquaternary ammonium muscarinic agonists have been developed over the last few years, but most of the existing compounds (e.g., arecoline, RS-86, AF-30) behave as weak partial agonists at cholinergic receptors in tissues of limited receptor reserve
- Saunders, John,Showell, Graham A.,Snow, Roger J,Baker, Raymond,Harley, Elizabeth A.,Freedman, Stephen B.
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p. 486 - 491
(2007/10/02)
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