1,1,3-Trioxo-2H,4H-Thieno[3,4-e][1,2,4]Thiadiazine (TTD) Derivatives: a New Class of Nonnucleoside Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase Inhibitors with Anti-HIV-1 Activity

We report the development of a new group of nonnucleoside reverse transcriptase inhibitors (NNRTIs). One of the most active congeners of this series of 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine (TTD) derivatives, i.e., 2-(3-fluorobenzyl)-4-cyanomethylen-1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine) (QM96639) was found to inhibit human immunodeficiency virus (HIV) type 1 [HIV-1 (III(B))] replication in MT-4 cells at a concentration of 0.09 μM. This compound was toxic for the host cells only at a 1,400-fold higher concentration. The TTD derivatives proved effective against a variety of HIV-1 strains, including those that are resistant to 3′-azido-3′-deoxythymidine (AZT), but not against HIV-2 (ROD) or simian immunodeficiency virus (SIV/MAC251). HIV-1 strains containing the L100I, K103N, V106A, E138K, Y181C, or Y188H mutations in their reverse transcriptase (RT) displayed reduced sensitivity to the compounds. Their cross-resistance patterns correlated with that of nevirapine. 2-Benzyl-4-cyanomethylen-1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine (QM96521) enhanced the anti-HIV-1 activity of AZT and didanosine in a subsynergistic manner. HIV-1-resistant virus containing the V179D mutation in the RT was selected after approximately six passages of HIV-1 (III(B)) in CEM cells in the presence of different concentrations of QM96521. From structure-activity relationship analysis of a wide variety of TTD derivatives, a number of restrictions appeared as to the chemical modifications that were compatible with anti-HIV activity. Modelling studies suggest that in contrast to most other NNRTIs, but akin to nevirapine, QM96521 does not act as a hydrogen bond donor in the RT-drug complex

Rheological behaviour of enzyme clarified Indian gooseberry juice

The rheological behaviour of enzyme clarified depectinated Indian gooseberry juice and its concentrate was studied as a function of total soluble solids concentration in the range of 8.2 to 35.9°Bx and temperatures from 20 to 80°C using coaxial controlled stress rheometer up to a shear rate of 600 s-1. The results indicated that the enzyme clarified gooseberry juice behaves like a Newtonian fluid with a viscosity ranging from 3.92 to 7.94 mPa s. The effect of temperature on viscosity of different concentration of juice was described by an Arrhenius type relationship (R >0.99). The activation energy for viscous flow was found to be in the range 4.34 to 5.37 KJ mol-1 depending upon the concentration of the juice. The activation energy of viscous flow on concentration was modeled by exponential equation (R>0.99). The effect of concentration on viscosity followed an exponential type relationship (R>0.98) at the temperature used

THE 400-KM SEISMIC DISCONTINUITY AND THE PROPORTION OF OLIVINE IN THE EARTHS UPPER MANTLE

The 400-km seismic discontinuity has traditionally been ascribed to the isochemical transformation of α-olivine to the β-modified-spinel structure in a mantle of peridotitic bulk composition1-6. It has recently been proposed7,8 that the observed seismic velocity increase at 400km depth is too abrupt and too small to result from a phase change in olivine but instead requires that the transition zone be chemically distinct in bulk composition from the uppermost mantle. By requiring phase relations in the Mg2SiO4-Fe2SiO4 system to be internally consistent thermodynamically, we find that the α-β transition in olivine of mantle (Mg0.9Fe0.1) 2SiO4 composition is extremely sharp, occurring over a depth interval (isothermal) of ∼6 km. The magnitude of the predicted velocity increase is in agreement with that observed seismically9,10 if the transition zone is composed of ∼60-70% olivine. Thus, our results indicate that seismic velocities across the 400-km discontinuity are consistent with a transition zone of homogeneous peridotitic composition and do not require chemical stratification. © 1986 Nature Publishing Group