title: Anti-inflammatory properties of new bioisosteres of indomethacin synthesized from safrole which are sulindac analogues.
abstract: The anti-inflammatory activities of new compounds (I, II, III and IV) synthesized in 30% overall yield from the abundant natural product safrole, the principal chemical constituent of the oil of sassafras (Ocotea pretiosa, Lauraceae), were determined in mice. The synthesis of these new indenyl-acetic acids (I and II) and indenyl-propionic acids (III and IV) was based on the minimal structural features of non-steroid anti-inflammatory agents of the aryl- or heteroarylcarboxylic acid group. The compounds exhibited potencies 4- to 10-fold less than that of indomethacin in inhibiting carrageenan-induced hindpaw edema. In contrast, like sulindac, all the new compounds were more potent than indomethacin in antagonizing writhing pain and increased vascular permeability caused by acetic acid. The results confirm the anticipated bioisosteric relationship between these synthetic derivatives, designed as sulindac analogues, and the classical non-steroidal anti-inflammatory agent, indomethacin.
authors.affiliation: Departamento de Farmacologia Básica e Clínica, Universidade Federal do Rio de Janeiro, Brasil.
authors.forename: E F
authors.initials: EF
authors.lastname: Pereira
authors.forename: N A
authors.initials: NA
authors.lastname: Pereira
authors.forename: M E
authors.initials: ME
authors.lastname: Lima
authors.forename: F A
authors.initials: FA
authors.lastname: Coelho
authors.forename: E J
authors.initials: EJ
authors.lastname: Barreiro
mesh_terms: D000698:Analgesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004149:Dioxoles / Q000378:metabolism*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D012451:Safrole / Q000031:analogs & derivatives / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013467:Sulindac / Q000031:analogs & derivatives*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004149:Dioxoles; D013467:Sulindac; D012451:Safrole; D007213:Indomethacin