AbstractCoupling of the 2‐hydrazinobenzoxazoles (I) with acrylonitrile (II) in the presence of a base gives the adducts (III).

3-[1-(2-Benzoxazolyl)hydrazino]propanenitrile derivatives were evaluated in the dermal and pleural reverse passive Arthus reactions in the rat. In the pleural test these compounds were effective in reducing exudate volume and accumulation of white blood cells. This pattern of activity was similar to that of hydrocortisone and different from that of indomethacin. The structural requirements for inhibiting the Arthus reactions were studied by systematic chemical modification of 1. These structure-activity relationship studies revealed that nitrogen 1' of the hydrazino group is essential for activity and must be electron rich, whereas chemical modifications of other sites of 1 had only a modest effect on activity.

The structural requirements for inhibition of RBL-1 (rat basophilic leukemia) 5-lipoxygenase by 15-hydroxyeicosa-5,8,11,13-tetraenoic acid (15-HETE, 1) were studied by systematic chemical modifications of the molecule at the hydroxyl and carboxyl groups, the double bonds, and the carboxylate and omega side chains. The most potent inhibitors were analogues that contained a 5,8-cis,cis-diene system and acted as alternate substrates for the enzyme. However, several analogues in which the 5,8-diene had been reduced were also found to inhibit the enzyme. Inhibition of 5-lipoxygenase by 15-hydroxyeicosa-11,13-dienoic acid (15-HEDE) analogues was optimal in compounds that generally contained a free carboxyl group, a carboxylate side chain of nine carbons, an omega side chain of five or six carbons, a cis,trans- or trans,cis-11,13-diene or 11,13-diyne system, and a 15-hydroxyl group. Conversion of 15-HEDE to its 16-membered lactone reduced but did not eliminate 5-lipoxygenase inhibitory activity. In contrast, a 3- to 10-fold enhancement of activity occurred when 5,15-diHETE (58) or 5-HETE (56) were cyclized to their respective delta-lactones. Molecular modeling of 15-HEDE analogues, modified in the C11-C15 region, showed that inactive analogues protrude into regions in space not occupied by active analogues. These structural studies indicate that multiple regions are important for 5-lipoxygenase inhibition by both 15-HETE and 15-HEDE analogues and that no single region plays a predominant role in inhibition.

2-[(Phenylthio)methyl]pyridine derivatives inhibited the dermal reverse passive Arthus reaction (RPAR) in the rat. In the same model, indomethacin was inactive, and hydrocortisone was active. Compounds Ia-d also significantly reduced exudate volume and white blood cell accumulation in the pleural RPAR. This pattern of activity was similar to that of hydrocortisone and different from that of indomethacin.

Die 3‐Brom‐3‐phenyl‐benzofuranone (I) reagieren mit 2‐Bromäthanol (II) zu den Substitutionsprodukten (III), die mit Alkoholaten in Methanol zu den Benzodioxepin‐5‐carbonsäurederivaten (IV) umlagem.

Das Benzofuranon (I) kann über das Anion allyliert und dann zu (II) benzyliert werden.

AbstractAus den Phenylbenzofuranonen (Ia)‐(Ic) entstehen mit Methallylchlorid die Substitutionsprodukte (IIa)‐(IIc); durch Substitution der phenolischen OH‐Gruppe in (IIc) entstehen die O‐Derivate (IId) und (IIe).

AbstractThe previously discovered neighboring group reaction has been extended to the synthesis of chroman derivatives (i.e., 4, 5, 6) containing geminal methyls in the 2‐position, a feature common to certain physiologically active natural chromans. In two instances, cyclic ortho ester by‐products (8), not observed in previous work, were formed as a result of the intramolecular trapping of tetrahedral intermediates. Reasons for the incursion of this unexpected side reaction are discussed.

AbstractA previously described neighboring group reaction has been extended to the synthesis of hydroxy‐substituted bridged 1,4‐benzoxazocines (i.e., 7, 8) bearing a structural analogy to potent analgetics of the hydroxy‐6,7‐benzomorphan series. In contrast to the latter, the presence of a hydroxyl group in the aromatic ring of the present series destroys all analgesic activity possessed by the unsubstituted system.

Journal of Heterocyclic ChemistryVolume 11, Issue 6 p. 1087-1089 Note 1,4-Benzodioxepins and 1,4-benzazepines from 3-phenyl-2-benzofuranones H. E. Zaugg, H. E. Zaugg Research Division, Abbott Laboratories, North Chicago, Illinois 60064Search for more papers by this authorJ. E. Leonard, J. E. Leonard Research Division, Abbott Laboratories, North Chicago, Illinois 60064Search for more papers by this authorR. W. Denet, R. W. Denet Research Division, Abbott Laboratories, North Chicago, Illinois 60064Search for more papers by this author H. E. Zaugg, H. E. Zaugg Research Division, Abbott Laboratories, North Chicago, Illinois 60064Search for more papers by this authorJ. E. Leonard, J. E. Leonard Research Division, Abbott Laboratories, North Chicago, Illinois 60064Search for more papers by this authorR. W. Denet, R. W. Denet Research Division, Abbott Laboratories, North Chicago, Illinois 60064Search for more papers by this author First published: December 1974 https://doi.org/10.1002/jhet.5570110645Citations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume11, Issue6December 1974Pages 1087-1089 RelatedInformation

AbstractAus den N‐Trichloräthyl‐benzamiden (II) erhält man mit Natriumhydrid in Dimethylformamid die Dichlor‐aziridine (III), während in 1,2‐Dimethoxy= äthan die Olefine (I) entstehen.

AbstractAus dem Dibromid (I) erhält man mit Methylat ausschließlich das Cyclisierungsprodukt (II), es entstehen keine Isomeren, die Reaktion verläuft stereospezifisch.