title: Inhibitors of immune complex-induced inflammation: 3-[1-(2-benzoxazolyl)hydrazino]propanenitrile derivatives.
abstract: The octanol-water partition coefficients (log P) and the dissociation constants (pKa) of 3-[1-(2-benzoxazolyl)hydrazino]propanenitrile analogues have been determined, and quantitative structure--activity relationships (QSAR) of the analogues as inhibitors of immune complex-induced inflammation have been studied. A significant correlation is observed between log P and pi substituent constants, and between pKa and inductive-field (F) and resonance (R) constants. The QSAR equations indicate that smaller substituents both at the 5-position and/or at the side chain tend to make the compound more potent, while an electron-withdrawing group at the side chain tends to make the compound less potent. The predicted potencies of 14 of 18 additional monosubstituted and all six disubstituted analogues agree reasonably well with the observed activities.
authors.affiliation: Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064.
authors.forename: K H
authors.initials: KH
authors.lastname: Kim
authors.forename: Y C
authors.initials: YC
authors.lastname: Martin
authors.forename: B
authors.initials: B
authors.lastname: Norris
authors.forename: F
authors.initials: F
authors.lastname: Haviv
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006834:Hydrazines / Q000627:therapeutic use*; D007105:Immune Complex Diseases / Q000150:complications*; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D009570:Nitriles / Q000627:therapeutic use*; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006834:Hydrazines; D009570:Nitriles; C060730:3-(1-(2-benzoxazolyl)hydrazino)propanenitrile