- HETEROCYCLIC DERIVATIVES
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The present invention relates to heterocyclic derivatives, and more particularly, to novel heterocyclic derivatives useful for the preparation of medicaments for treating diseases related to uric acid.
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Page/Page column 16
(2011/02/25)
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- Non-imidazole histamine H3 ligands. Part III. New 4-n-propylpiperazines as non-imidazole histamine H3-antagonists
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In search for a new lead of non-imidazole histamine H3-receptor antagonists, a series of 1[(2-thiazolopyridine)-4-n-propyl]piperazines, the analogous 1-[(2-oxazolopyridine)-4-npropyl]piperazines, 1-[(2-benzothiazole)-4- n-propyl]piperazine and 1-[(2-benzooxazole)4-n-propyl]piperazine were prepared and in vitro tested as H3-receptor antagonists (the electrically evoked contraction of the guinea-pig jejunum). It appeared that by comparison of homologous pairs the thiazolo derivatives have slightly higher activity than their oxazolo analogues. The most potent compound of these series is the 1-(2-thiazolo[4,5-c]pyridine)-4-n-propylpiperazine (3c) with pA2 = 7.25 (its oxazole analogue (4g) showed pA2 = 6.9). The structure-activity relationships for compounds with various positions of the nitrogen in the benzene ring for the thiazoles compared with oxazoles are discussed.
- Walczyski, Krzysztof,Zuiderveld, Obbe P.,Timmerman, Henk
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- Aminopyridine carbamic acid esters: Synthesis and potential as acetylcholinesterase inhibitors and acetylcholine releasers
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4-Amino-3-pyridyl carbamates (2a-c) were synthesized as potential acetylcholinesterase inhibitors and acetylcholine releasers on the basis of the reported activity of the analogous N-(4-amino-3-pyridyl)-N',N'- dimethylurea (1). Although 4-amino-3-pyridyl N,N-dimethylcarbamate (2b) showed good cholinesterase inhibition [concentration that elicited a 50% reduction in the maximal enzyme response (IC50) was 13.4 μM], it had no effect on the stimulated release of [3H]acetylcholine from rat striatal slices. 4-[[(Dimethylamino)methylene]amino]-3-pyridyl N,N-dimethylcarbamate (7a), an intermediate in the synthesis of 2b, demonstrated surprisingly good cholinesterase inhibition (IC50 was 9.4 μM) but showed no activity as a releaser. A precursor to 7a, N-(3-hydroxy-4-pyridyl)-N',N'- dimethylformamidine (6a), showed some activity in release but was not an esterase inhibitor, whereas the precursor to 6a, 4-amino-3-pyridinol (5a), was a potent releaser. A new synthesis of 5a, based on an ortho-directed lithiation strategy, is also reported.
- Shutske,Tomer,Kapples,Hrib,Jurcak,Bores,Huger,Petko,Smith
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p. 380 - 385
(2007/10/02)
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