- GEMINAL SUBSTITUTED QUINUCLIDINE AMIDE COMPOUNDS AS AGONISTS OF ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTORS
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The present invention relates to novel geminal substituted quinuclidine amide compounds, and pharmaceutical compositions of the same, that are suitable as agonists or partial agonists of α7- nAChR, and methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering the compound or composition to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom.
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Paragraph 00399-00400
(2016/07/05)
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- Phosphodiesterase inhibitors. Part 5: Hybrid PDE3/4 inhibitors as dual bronchorelaxant/anti-inflammatory agents for inhaled administration
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(-)-6-(7-Methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-4-yl) -5-methyl-4,5-dihydropyridazin-3(2H)-one (KCA-1490) exhibits moderate dual PDE3/4-inhibitory activity and promises as a combined bronchodilatory/anti- inflammatory agent. N-alkylation of the pyridazinone ring markedly enhances potency against PDE4 but suppresses PDE3 inhibition. Addition of a 6-aryl-4,5-dihydropyridazin-3(2H)-one extension to the N-alkyl group facilitates both enhancement of PDE4-inhibitory activity and restoration of potent PDE3 inhibition. Both dihydropyridazinone rings, in the core and extension, can be replaced by achiral 4,4-dimethylpyrazolone subunits and the core pyrazolopyridine by isosteric bicyclic heteroaromatics. In combination, these modifications afford potent dual PDE3/4 inhibitors that suppress histamine-induced bronchoconstriction in vivo and exhibit promising anti-inflammatory activity via intratracheal administration.
- Ochiai, Koji,Takita, Satoshi,Kojima, Akihiko,Eiraku, Tomohiko,Iwase, Kazuhiko,Kishi, Tetsuya,Ohinata, Akira,Yageta, Yuichi,Yasue, Tokutaro,Adams, David R.,Kohno, Yasushi
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p. 375 - 381
(2013/02/23)
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- Halogenated analogs of 1′-acetoxychavicol acetate, Rev-export inhibitor from Alpinia galanga, designed from mechanism of action
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In the course of search for the robust analogs of 1′-acetoxychavicol acetate (ACA, 1), the Rev-export inhibitor from the medicinal plant Alpinia galanga, we clarified formation of the quinone methide intermediate ii to be essential for exerting the inhibi
- Tamura, Satoru,Shiomi, Atsushi,Kimura, Tominori,Murakami, Nobutoshi
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scheme or table
p. 2082 - 2085
(2010/07/05)
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- PYRAZOLONE DERIVATIVE AND PDE INHIBITOR CONTAINING THE SAME AS ACTIVE INGREDIENT
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It is to provide a novel pyrazolone derivative represented by the following general formula (1), which is useful as a pharmaceutical and has a phosphodiesterase inhibitory action: wherein R1,R2: C1-6 alkyl; R3,R4: H, X, C1-6 alkoxy; Z:O, S; A:AA, BB, wherein AA represents wherein BB represents wherein R5: H, C1-6 alkyl ; R6,R7: C1-6 alkyl.
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Page/Page column 136
(2010/04/25)
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- Cycloalkyl alkanoic acids as integrin receptor antagonists derivatives
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The present invention relates to a class of compounds represented by the Formula I or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of the Formula I, and methods of selectively inhibiting or antagonizing the αvβ3 and/or αvβ5 integrin.
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- Synthesis and anticancer activity of fluorinated analogues of combretastatin A-4
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The synthesis of a series of fluorinate d benzaldehydes and their use in the Wittig synthesis of fluoro-substituted stilbenes is described. 3,5-Difluoro-4-hydroxybenzaldehyde (6) and 3-fluoro-4-methoxybenzaldehyde (11) are prepared by Duff formylation of 3,5-difluorophenol and 2-fluoroanisole, respectively. 2-Methoxy-3,4-difluorobenzaldehyde was obtained by Friedel-Crafts formylation of 2,3-difluoroanisole with α,α-dichloromethyl methyl ether. The aldehydes were used to make a series of fluorinated analogues of the anticancer combretastatins A-1, A-2 and A-4. The in vitro anticancer properties of the fluoro combretastatins are reported. The most active fluoro analogue 3-deoxy-3-fluoro-combretastatin A-4 (Z-2) retains the potent cell growth inhibitory properties of CA-4.
- Lawrence, Nicholas J.,Hepworth, Lucy A.,Rennison, David,McGown, Alan T.,Hadfield, John A.
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p. 101 - 108
(2007/10/03)
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