- Design and synthesis of [(2,3-dichlorophenyl)piperazin-1-yl]alkylfluorenylcarboxamides as novel ligands selective for the dopamine D3 receptor subtype
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The dopamine D3 receptor subtype has been recently targeted as a potential neurochemical modulator of the behavioral actions of psychomotor stimulants, such as cocaine. However, definitive behavioral investigations have been hampered by the lack of highly selective D3 agonists and antagonists. In an attempt to design a novel class of D3 ligands with which to study this receptor system, a series of chemically divergent compounds that possessed various structural features that exist within several classes of reputed D3 agents was screened and compared to the recently reported NGB 2904 (58b). On the basis of these results, a novel series of compounds was designed that included functional moieties that were required for high-affinity and selective binding to D3 receptors. All the compounds in this series included an aryl-substituted piperazine ring, a varying alkyl chain linker (C3-C5), and a terminal aryl amide. The compounds were synthesized and evaluated in vitro for binding in CHO cells transfected with human D2, D3, or D4 receptor cDNAs. D3 binding affinities ranged from Ki=1.4 to 1460 nM. The most potent analogue in this series, 51, demonstrated a D3/D2 selectivity of 64 and a D3/D4 selectivity of 1300. Structure-activity relationships for this class of ligands at D3 receptors will provide new leads toward the development of highly selective and potent molecular probes that will prove useful in the elucidation of the role D3 receptors play in the psychomotor stimulant and reinforcing properties of cocaine.
- Robarge,Husbands,Kieltyka,Brodbeck,Thurkauf,Newman
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p. 3175 - 3186
(2007/10/03)
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- Anti-viral method
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PCT No. PCT/US97/07431 Sec. 371 Date Jan. 6, 1999 Sec. 102(e) Date Jan. 6, 1999 PCT Filed May 2, 1997 PCT Pub. No. WO97/41846 PCT Pub. Date Nov. 13, 1997The present invention provides compounds which inhibit an envelope virus by inhibiting the fusion of the virus with the host cell. The virus may be inhibited in an infected cell, a cell susceptible of infection or a mammal in need thereof.
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- Urea, thiourea and guanidine compounds and their use as anti-viral agents
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The present invention provides compounds which inhibit an envelope virus by inhibiting the fusion of the virus with the host cell. The virus may be inhibited in an infected cell, a cell susceptible of infection or a mammal in need thereof.
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- New Triazine Derivatives as Potent Modulators of Multidrug Resistance
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A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity.Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5μM in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin.The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators.In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the T/C by 39percent in mice bearing the resistant tumor cell line P388/VCR.According to these interesting properties, 16 was selected for a clinical development because it is more bioavailable than 34, even though it was less active.
- Dhainaut, Alain,Regnier, Gilbert,Atassi, Ghanem,Pierre, Alain,Leonce, Stephane,et al.
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p. 2481 - 2496
(2007/10/02)
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- N,N-Bis(trimethylsilyl)methoxymethylamine as a Convenient Synthetic Equivalent for +CH2NH2: Primary Aminomethylation of Organometallic Compounds
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The introduction of the primary aminomethyl unit at carbon through N,N-bis(trimethylsilyl)aminomethylation of Grignard and organolithium compounds can be achieved in good yield using N,N-bis(trimethylsilyl)methoxymethylamine (1).
- Morimoto, Toshiaki,Takahashi, Toshio,Sekiya, Minoru
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p. 794 - 795
(2007/10/02)
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- A Base-labile Amine Component in Four-component Condensation (4CC) Synthesis
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The use of 9-aminomethylfluorene as the amine component in four-component condensation (4CC) synthesis is described for a model peptide synthesis.
- Hoyng, Charles F.,Patel, Arvind D.
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p. 491 - 492
(2007/10/02)
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