64015-88-9Relevant academic research and scientific papers
Thiazolothiazepine inhibitors of HIV-1 integrase
Neamati, Nouri,Turpin, Jim A.,Winslow, Heather E.,Christensen, John L.,Williamson, Karen,Orr, Ann,Rice, William G.,Pommier, Yves,Garofalo, Antonio,Brizzi, Antonella,Campiani, Giuseppe,Fiorini, Isabella,Nacci, Vito
, p. 3334 - 3341 (2007/10/03)
A series of thiazolothiazepines were prepared and tested against purified human immunodeficiency virus type-1 integrase (HIV-1 IN) and viral replication. Structure-activity studies reveal that the compounds possessing the pentatomic moiety SC(O)CNC(O) with two carbonyl groups are in general more potent against purified IN than those containing only one carbonyl group. Substitution with electron-donating or -withdrawing groups did not enhance nor abolish potency against purified IN. By contrast, compounds with a naphthalene ring system showed enhanced potency, suggesting that a hydrophobic pocket in the IN active site might accommodate an aromatic system rather than a halogen. The position of sulfur in the thiazole ring appears important for potency against IN, as its replacement with an oxygen or carbon abolished activity. Further extension of the thiazole ring diminished potency. Compounds 1, 19, and 20 showed antiviral activity and inhibited IN within similar concentrations. These compounds inhibited IN when Mn2+ or Mg2+ was used as cofactor. None of these compounds showed detectable activities against HIV-1 reverse transcriptase, protease, virus attachment, or nucleocapsid protein zinc fingers. Therefore, thiazolothiazepines are potentially important lead compounds for development as inhibitors of IN and HIV replication.
Conformationally restricted analogues of remoxipride as potential antipsychotic agents
Norman,Kelley,Hollingsworth
, p. 3417 - 3423 (2007/10/02)
Several conformationally restricted derivatives of (S)-3-bromo-N-((1- ethyl-2-pyrrolidinyl)methyl)-2,6-dimethoxybenzamide (remoxipride) were synthesized and evaluated in vitro for their ability to inhibit [3H]raclopride binding at the dopamine D-2 receptor. The cyclic benzamides designed to mimic the intramolecular hydrogen bonding of desmethylremoxipride (4, FLA-797) included 2,3-dihydro-4H-1,3-benzoxazin-4-ones, 2,3-dihydro-4H- 1,3-benzthiazin-4-ones, phthalimides, 1-isoindolinones, 1,2-benzisothiazol- 3(2H)-ones, and 1,2-benzisothiazol-3(2H)-one 1,1-dioxides. In this series, enhanced affinities to the dopamine D-2 receptor were not observed. The phthalimidine analogue 24b ((S)-6-chloro-2-(1-ethylpyrrolidinyl)-1- isoindolinone) exhibited the highest affinity to the dopamine D-2 receptor with an IC50 of 1.3 μM, which was equipotent to remoxipride.
