- Fused imidazopyridine derivatives as antihyperlipidemic agents
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A novel compound of the formula: wherein ring Q is an optionally substituted pyridine ring; One of R0, R1and R2is —Y0—Z0, and the other tow groups are a hydrogen, a halogen, an optionally substituted hydroxy group, a hydrocarbon group that may be an optionally substituted hydrocarbon group or an acyl group; Y0is a bond or an optionally substituted bivalent hydrocarbon group; Z0is a basic group which may be bonded via oxygen, nitrogen, —CO—, —CS—, —SO2N(R3)— (where R3is hydrogen or an optionally substituted hydrocarbon group), or S(O)n(wherein n is to 0, 1 or 2); .........is a single bond or a double bond, or a salt thereof, which has an excellent LDL receptor up-regulating, blood-lipids lowering, blood-sugar lowering and diabetic complication-ameliorating activity.
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- Synthesis and structure-activity relationships of naphthamides as dopamine D3 receptor ligands
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A series of naphthamides were synthesized, and the affinities of these compounds were determined for dopamine D2 and D3 receptors using radioligand binding techniques. The naphthamide compounds that were prepared include N-(1- alkylp
- Huang,Luedtke,Freeman,Wu,Mach
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p. 1815 - 1826
(2007/10/03)
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- Synthesis and structure-activity relationships of N-(1-benzylpiperidin-4-yl)arylacetamide analogues as potent σ1receptor ligands
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A series of N-(1-benzylpiperidin-4-yl)arylacetamides were synthesized and evaluated for their binding properties for σ1 and σ2 receptors. In agreement with previously reported σ1/σ2 receptor binding data for N-(1-benzylpiperidin-4-yl)phenylacetamide, all of the N-(1-benzylpiperidin-4-yl)arylacetamide compounds reported below displayed higher affinity for σ1 vs σ1 receptors. Replacement of the phenyl ring of the phenylacetamide moiety with a thiophene, naphthyl, or indole aromatic ring had no significant effect on the σ1 receptor affinity. Replacement of the phenyl ring with an imidazole or pyridyl aromatic ring resulted in a >60-fold loss in affinity for σ1 receptors and no significant binding affinity for σ2 receptors. Substitution on the aromatic ring of the benzyl group showed a similar or slightly decreased affinity for σ1 receptors. Substitution on the aromatic rings of both the phenylacetamide moiety and the benzyl group with a halogen resulted in a similar affinity for σ1 receptors and a significantly increased affinity for σ2 receptors. Comparative molecular field analysis revealed that electrostatic properties of the substituents in the phenylacetamide aromatic ring strongly influenced binding to σ1 receptors. Compounds 1, 10, 18, 22, 37, and 40 showed the highest selectivity for σ1 receptors with Ki (σ2) to Ki (σ1) ratios of 100, >92, >122, 77, 74, and 80, respectively. In agreement with previously reported results, the phenylacetamide analogues had no binding affinity for dopamine receptors (D2/D3).
- Huang,Hammond,Wu,Mach
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p. 4404 - 4415
(2007/10/03)
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- Synthesis and gastrointestinal prokinetic activity of novel benzamide derivatives with amphoteric side chains
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Novel benzamide derivatives (19-24, 32a-c, 43d-f), each possessing a cycloaminoalkanecarboxylic acid side chain, were synthesized and their gastrointestinal prokinetic and dopamine D2 receptor antagonist activities were evaluated. 4-[(4-Amino-5
- Sakaguchi,Iwasaki,Iwanaga,Saito,Takahara,Kato,Hanaoka
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p. 424 - 436
(2007/10/03)
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- 18F-labeled benzamides for studying the dopamine D2 receptor with positron emission tomography
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Two series of (N-benzylpiperidin-4-yl)- and (9-azabicyclo[3.3.1]nonan- 3β-yl)benzamides were prepared, and in vitro binding assays were used to measure the affinity of these compounds for dopamine D2, dopamine D3, serotonin 5-HT2, and α2-adrenergic receptors. The results of these studies indicated compounds 23, 26b, and 34 have the selectivity needed for in vivo studies of the D2 (and possibly D3) receptors. 18F-Labeled analogues of 23, 26b and 34 were prepared by N-alkylation of the corresponding desbenzyl precursors with [18F]-4-fluorobenzyl iodide. Preliminary in vivo studies demonstrated that [18F]-23 and [18F]-26b are suitable candidates for further evaluation in positron emission tomography imaging studies. The slow rate of washout of [18F]-34 from nondopaminergic regions and its comparatively high lipophilicity indicates that this compound may not be suitable for imaging studies because of a high level of nonspecific binding.
- Mach,Leudtke,Unsworth,Boundy,Nowak,Scripko,Elder,Jackson,Hoffman,Evora,Rao,Molinoff,Childers,Ehrenkaufer
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p. 3707 - 3720
(2007/10/02)
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- New cinnamoic compounds, the process for preparing same and the use thereof in therapeutics
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Compounds of formula: STR1 wherein: Ar is an aromatic group; R and R1 are H or CH3 ; A represents a nitrogenized heterocyclic radical; B is OH or forms with the adjacent CO group, either an amido group, or a carbonyloxy group; R
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