This paper reviews the blood-brain barrier (BBB) penetration of newly developed pyridinium aldoximes. Pyridinium aldoximes are highly charged hydrophilic compounds used in the treatment of subjects exposed to organophosphonates because they are effective as acetylcholinesterase reactivators. Pyridinium aldoximes have antidotal effects against poisoning with cholinesterase inhibitors, a frequent problem affecting people working with organophosphate-based insecticides and pesticides. Toxic organophosphonate products such as sarin and tabun can be used by terrorists as chemical warfare agents. This poses a severe challenge to all innocent and peace-loving people worldwide. This review gives a brief summary of BBB transporters and description of the current in vitro and in vivo methods for the characterization of BBB penetration of established and novel pyridinium aldoximes. The authors provide a putative mechanism of penetration, outline some future ways of formulation and discuss the possible advantages and disadvantages of increasing BBB penetration.

Gellert-t. 4 S. Antus, Chinoin Pharmaceutical and Chemical Works, Budapest, IV. T6-u. 1-4 2'-Benzoyloxy-7-benzyloxy-4',5-dimethoxy-2-methoxycarbonylisoflavone (1 2), prepared in nine steps by established methods, has been degraded to the corresponding phenyl benzyl ketone (9). which cyclises on treatment with ethyl formate and sodium to give 7-benzyloxy-2'-hydroxy-4',5-dimethoxyisoflavone (1 5) ; the latter has been converted in four steps into 2',5,7-trihydroxy-4'-methoxyisoflavanone (1 ), identical with natural ferreirin.(k)-Dalbergioidin has been prepared by hydrogenation and subsequent saponification of 2',4',5,7-tetra-acetoxyisoflavo ne.3-Methyl-2,4,6-trihydroxyphenyl 2.4-dimetlioxybenzyl ketone ( 21), when treated with ethoxalyl chloride, gives mainly 2-ethoxycarbonyl-5,7-dihydroxy-2',4'-dimethoxy-6-methylisoflavone (23), which has been transformed in six steps into (~)-2',4',5-trihydroxy-7-methoxy-6-methylisoflavanone, (%)-ougenin (20).THE natural occurrence of nine isoflavanones, padmakastein,2 ferreirin (l), homoferreirin (2), dalbergioidin (19), ougenin (20), sophor01,~ nepseudin,6 neot enon ,6 and 6,7-dimethoxy-3',4'-methylenedioxyisoflavanone,' has been recorded. The occurrence of padmakastein (4',5-dihydroxy-7-methoxyisoflavanone) could not later be confirmed.8 H~moferreirin,~ nepseudin,1° ougenin,ll and 6,7-dimethoxy-3',4'-methylenedioxyisoflavanone have been synthesized. We report here syntheses of ferreirin and dalbergioidin, and a new synthesis of ougenin.Ferreiriiz. -Racemic f erreirin, 2', 5,7-t rihydroxy-4'methoxyisoflavanone (1), and its 2'-methyl ether, honioferreirin (2), have been isolated from the heartwoodof Ferreirea ~+ectabiZis.~ 7 Our synthesis of ferreirin employed 2-hydroxy-4-methoxybenzaldehyde l2 (3), which was converted by benzylation [product (4)] and a subsequent simplified azlactone synthesis l3 into the nitrile (5). Since compound (5) did not react with phloroglucinol under the conditions of the Hoesch synthesis,14 it was converted by way of the hydroxyt The optical activity of compound (I) was not reported, but we found that a sample of the natural product showed no optical rotation down to 300 nm.

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