3-[1-(2-Benzoxazolyl)hydrazino]propanenitrile derivatives: inhibitors of immune complex induced inflammation.
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.
Haviv
F
F
Abbott Laboratories, Abbott Park, Illinois 60064.
Ratajczyk
J D
JD
DeNet
R W
RW
Kerdesky
F A
FA
Walters
R L
RL
Schmidt
S P
SP
Holms
J H
JH
Young
P R
PR
Carter
G W
GW
D000818:Animals; D000893:Anti-Inflammatory Agents; D001183:Arthus Reaction / Q000188:drug therapy*; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000627:therapeutic use*; D055598:Chemical Phenomena; D002621:Chemistry; D006834:Hydrazines / Q000138:chemical synthesis / Q000627:therapeutic use; D006854:Hydrocortisone / Q000627:therapeutic use; D007105:Immune Complex Diseases / Q000188:drug therapy; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D009570:Nitriles / Q000138:chemical synthesis / Q000627:therapeutic use*; D010995:Pleural Diseases / Q000276:immunology; D051381:Rats; D012871:Skin Diseases / Q000276:immunology; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D001583:Benzoxazoles; D006834:Hydrazines; D009570:Nitriles; D006854:Hydrocortisone; D007213:Indomethacin