title: N-(4-Isoxazolylthiazol-2-yl)oxamic acid derivatives as potent orally active antianaphylactic agents.
abstract: A series of N-(4-isoxazolylthiazol-2-yl)oxamic acid derivatives was synthesized and tested on the passive cutaneous anaphylaxis (PCA) model in rats to verify its potential antianaphylactic activity. These compounds were prepared by reaction of an appropriate bromoacetylisoxazole with thiourea to give the corresponding aminothiazole and subsequent condensation with an oxalic acid monoester chloride to yield, following the usual process, the oxamic acid derivatives. Most of the new compounds exhibited, by intraperitoneal route in rats, a very potent antianaphylactic activity on PCA response, higher than that of the reference compound disodium cromoglycate (DSCG). The new derivatives, in contrast with DSCG, were effective on PCA even by oral route. The most interesting derivative of the new series was N-[4-(3-methyl-5-isoxazolyl)-2-thiazolyl]oxamic acid 2-ethoxyethyl ester (49), which was also active and more potent than DSCG in experimental models involving either IgE- or IgG-mediated anaphylactic responses at bronchopulmonary level.
authors.affiliation: Zambon Group Spa, Milano, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Chiarino
authors.forename: G
authors.initials: G
authors.lastname: Grancini
authors.forename: V
authors.initials: V
authors.lastname: Frigeni
authors.forename: I
authors.initials: I
authors.lastname: Biasini
authors.forename: A
authors.initials: A
authors.lastname: Carenzi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004205:Cromolyn Sodium / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D010072:Oxamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: D006633:Histamine Antagonists; D007555:Isoxazoles; D013189:SRS-A; C067390:2-ethoxyethyl N-(4-(3-methyl-5-isoxazolyl)-2-thiazolyl)oxamate; D004205:Cromolyn Sodium; D010072:Oxamic Acid