- Iridium-catalyzed enantioselective hydrogenation of unsaturated heterocyclic acids
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Spiral binding: A highly enantioselective hydrogenation of unsaturated heterocyclic acids has been developed by using chiral iridium/spirophosphino oxazoline catalysts (see scheme; BArF-=tetrakis[3,5- bis(trifluoromethyl)phenyl]borate, Boc=tert-butoxycarbonyl). This reaction provided an efficient method for the preparation of optically active heterocyclic acids with excellent enantioselectivities. Copyright
- Song, Song,Zhu, Shou-Fei,Pu, Liu-Yang,Zhou, Qi-Lin
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supporting information
p. 6072 - 6075
(2013/07/05)
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- THERAPEUTIC COMPOUNDS AND USES THEREOF
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Compounds of formula (I) are described herein The compounds can be used, for example, to modulate growth hormone secretagogue receptor (GHS-R). In some instances, the compounds can be used to treat obesity.
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Page/Page column 95
(2008/06/13)
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- New carbamoylpiperidines as human platelet aggregation inhibitors
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A series of 3-carbamoylpiperidines (nipecotamides) are designed, synthesized and tested for their inhibitory action against adenosine diphosphate (ADP)-induced aggregation of human platelets. A structure- activity analysis of the bis(nipecotamido)aralkane type showed that a substituent on the piperidine ring should preferably be an amide and that the electronegativity of the carbonyl oxygen and the orientation of the amide group affected activities. Based on the knowledge of factors influencing platelet activation and aggregation, a nitric ester moiety which could release nitric oxide (NO) in situ, is incorporated into the nipecotamide structure. These compounds exhibit increased activity compared to those having no -ONO2 function. They also show stereoselectivity, with the meso isomer being approximately twice as potent as the synthetic diastereomeric mixture. Replacement of the -ONO2 function with hydroxyl, ester or alkyl groups considerably diminishes aggregation-inhibitory potential. Nipecotamides are shown here to inhibit the basal and collagen-induced rise in platelet inositol trisphosphate (IP3) levels, as well as phosphoinositide turnover. A comprehensive mechanism of action is proposed taking earlier results into consideration. (C) 2000 Elsevier Science Ltd.
- Guo, Zhengming,Zheng, Xiaozhang,Thompson, Walter,Dugdale, Marion,Gollamudi, Ram
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p. 1041 - 1058
(2007/10/03)
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- Synthesis and muscarinic activity of a series of tertiary and quaternary N-substituted guvacine esters structurally related to arecoline and arecaidine propargyl ester
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A series of tertiary and quaternary N-substituted guvacine (1,2,5,6-tetrahydro-3-carboxy-pyridine) methyl and propargyl esters have been synthesized and tested for muscarinic/antimuscarinic activity on rat ileum and electrically paced left atria. Arecoline and arecaidine propargyl ester (APE) as well as their corresponding N-demethyl derivatives, guvacoline (norarecoline) and guvacine propargyl ester, acted as full agonists at both atrial and ileal muscarinic receptors (range of pD2-values 6.09-8.07). However, in both preparations arecoline and APE were clearly more potent (up to 15-fold) than their N-demethyl analogues. Replacement of the N-methyl group in arecoline and APE by larger substituents (ethyl, n-propyl, n-butyl, benzyl, phenylethyl) as well as N-methylation resulted in a decrease or even a complete loss of agonistic activity. In both organs, the propargyl esters usually showed higher potency than the corresponding methyl ester analogues. N-Ethylguvacine propargyl ester and APE methiodide displayed pronounced agonistic activity in the atria (pD2 ? 6.5; intrinsic activity = 0.79 and 0.67, respectively) but behaved as competitive antagonists in the ileum (pA2 = 6.06 and 5.62, respectively). Beside the lower sensitivity to muscarinic agonists of the rat ileum as compared to rat atria, the cardioselective stimulant action of both agents may also be due to their ability to recognize structural differences between atrial M(2α) and ileal M(2β) muscarinic receptor subtypes.
- Wolf-Pflugmann,Lambrecht,Wess,Mutschler
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p. 539 - 544
(2007/10/02)
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