Xoma Corporation

Sri International

Dane A Goff

Dayton T Reardan

Stephen Fitzhugh Carroll

Ralph New Harris, Iii

Gary A Koolpe

Clifford D Bedford

Richard A Kenley

Duane E Hilmas

Robert A Howd

Robert O Pick

Macromolecular species such as enzymes, proteins, drugs, and solid supports which contain reactive carbonyl groups or groups which are readily converted to reactive carbonyl groups are modified by reaction with a compound of the formula ##STR1## in which R.sup.1 is H, C.sub.1 -C.sub.20 alkyl, phenyl, (C.sub.1 -C.sub.10 alkyl)-substituted phenyl, or phenyl-substituted C.sub.1 -C.sub.10 alkyl; R.sup.2 is C.sub.2 -C.sub.5 alkylene or (C.sub.1 -C.sub.4 alkoxy)-substituted C.sub.2 -C.sub.5 alkylene; R.sup.3 is ##STR2## R.sup.4 is H or C.sub.1 -C.sub.4 alkyl; n is at least 5; and m is zero or 1.

Activated polymers and conjugates thereof

Compounds containing carbohydrate moieties or carboxyl groups are linked to either compounds containing thiol moieties or electron-deficient moieties by the use of linking agents of the formula ##STR1## in which R.sup.1 is NH.sub.2 -- or NH.sub.2 --NH--; R.sup.2 is --NH--C(O)--, --C(O)--NH--, or --C(O)--; R.sup.3 is C.sub.1 -C.sub.10 alkylene, C.sub.5 -C.sub.7 cyclic alkylene, arylene, phenyl-substituted C.sub.1 -C.sub.10 alkylene, benzyl-substituted C.sub.1 -C.sub.10 alkylene, or amino-substituted C.sub.1 -C.sub.10 alkylene; R.sup.4 is H, acetyl, ##STR2## where R.sup.5 is C.sub.1 -C.sub.5 alkyl; m is zero or 1; and n ia zero or 1.

Linking agents and methods

Novel compounds and methods for the formation of disulfide linkages are presented. The novel compounds employed are substituted 2-iminothiolane hydrohalide linking agents of the following formula (I): ##STR1## wherein, X is halogen;

Hindered linking agents and methods

Macromolecular species such as enzymes, proteins, drugs, and solid supports which contain reactive carbonyl, groups or groups which are readily converted to reactive carbonyl groups are modified by reaction with a compound of the formula ##STR1## in which R.sup.1 is H, C.sub.1 -C.sub.20 alkyl, phenyl, (C.sub.1 -C.sub.10 alkyl)-substituted phenyl, or phenyl-substituted C.sub.1 -C.sub.10 alkyl; R.sup.2 is C.sub.2 -C.sub.5 alkylene or (C.sub.1 -C.sub.4 alkoxy)-substituted C.sub.2 -C.sub.5 alkylene; R.sup.3 is ##STR2## R.sup.4 is H or C.sub.1 -C.sub.4 alkyl; n is at least 5; and m is zero or 1.

Hindered linking agents derived from 2-iminothiolanes and methods

Activated polyers and conjugates thereof

Compounds containing carbohydrate moieties or carboxyl groups are linked to either compounds containing thiol moieties or electron-deficient moieties by the use of linking agents of the formula ##STR1## in which R.sup.1 is NH.sub.2 -- or NH.sub.2 --NH--; R.sup.2 is --NH--C(O)--, --C(O)--NH--, or --C(O)--; R.sup.3 is C.sub.1 -C.sub.10 alkylene, C.sub.5 -C.sub.7 cyclic alkylene, arylene, phenyl-substituted C.sub.1 -C.sub.10 alkylene, benzyl-substituted C.sub.1 -C.sub.10 alkylene, or amino-substituted C.sub.1 -C.sub.10 alkylene; R.sup.4 is H, acetyl, ##STR2## where R.sup.5 is C.sub.1 -C.sub.5 alkyl; m is zero or 1; and n is zero or 1.

A therapeutically effective class of low toxicity aldoxime-substituted functionalized imidazolium compounds and compositions is disclosed which is effective in the treatment of living species poisoned by organophosphorus chemicals which inactivate the enzyme acetylcholinesterase. In vivo administration of therapeutically effective amounts of these aldoxime-substituted imidazolium derivatives has been found to save mammals having inhibited acetylcholinesterase due to injection with lethal dosages of Soman.

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Menlo Park, CA, United States of America

Dane A Goff