Macrosorb Kieselguhr-agarose composite adsorbents. New tools for downstream process design and scale up. Scientific note.

Incompressible Macrosorb composite adsorbents, while retaining all the desirable properties of traditional agarose-based hydrogel media, overcome the operational limitations imposed by the use of soft hydrogels: They permit useful application of fast flow rates without restrictions on bed depth and they can be used in fluidized bed mode. Considerations which are important when contemplating scaled-up processing are discussed. A comparative cost estimate for a production process for extracting albumin from bovine serum in column equipment illustrates the various advantages which may be exploited when using a composite adsorbent in place of a conventional soft gel equivalent.

Acidic epinephrine analogues derived from 1H, 3H-2,1,3-benzothiadiazole 2,2-dioxide and from trifluoromethanesulfonanilide. A new synthesis of 1H,3H-2,1,3-benzothiadiazole 2,2-dioxide.

Treatment of N,N'-dibenzyl-1,2-diaminobenzene (2) successively with thionyl chloride and then m-chloroperbenzoic acid gave N,N'-dibenzyl-1H,3H-2,1,3-benzothiadiazole 2,2-dioxide (4), which gave (via routes analogous to standard epinephrine syntheses) four bicyclic catecholamine analogues 7a-d. Hydrogenolysis of 4 yielded the parent heterocycle 5 in the first practicable synthesis avoiding expensive sulfamide (Scheme I). The trifluoromethanesulfonamidoacetophenones 8m and 8p on similar elaboration gave triflanilide catecholamine analogues 14m, 14p,17m, and 17p (Scheme II). 4,4'Dimethoxybenzhydrylamine (15) is recommended for the regiospecific synthesis of primary amines from epoxides (Scheme II). Series 7,14, and 17 were inactive in animal cardiovascular screens. Selected compounds were also screened in bronchodilator and in in vitro dopamine-, clonidine-, and prazosin-receptor binding assays as appropriate; again no activity was observed. Steric lipophilicity, and acidity factors are discussed, and the inactivity is ascribed to the high acidity of both systems (pKa approximately equal to 4).