Ro 22-3747: a new antiallergic agent for the treatment of immediate hypersensitivity diseases.

Ro 22-3747 was orally active in two animal models of immediate hypersensitivity diseases mediated by immunoglobulin E: the rat passive cutaneous anaphylaxis test (ID50 of 0.65 mg/kg) and a model in which anaphylactic bronchospasm was studied in passively sensitized rats (ID50 of 0.022 mg/kg).

(E)-3-(4-Oxo-4H-quinazolin-3-yl)-2-propenoic acids, a new series of antiallergy agents.

A series of substituted (E)-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acids was prepared and evaluated in the rat passive cutaneous anaphylaxis (PCA) test for antiallergic activity. Alkoxy, alkylthio, and isopropyl substituents at the 6- or 8-positions provided highly potent compounds. Conversion to the Z isomer, reduction of the side chain double bond, or reduction of the quinazoline ring resulted in substantial loss of activity.

Synthesis and pharmacology of metabolically stable tert-butyl ethers of morphine and levorphanol.

3-O-tert-Butylmorphine (5) was prepared from 6-O-acetylmorphine (3) via alkylation with N,N-dimethylformamide di-tert-butyl acetal, followed by hydrolytic removal of the 3-(dimethylamino)-2-propenoate group. The same process was used to prepare the tert-butyl ether of levorphanol (6), (-)-3-tert-butoxy-N-methylmorphinan (8). Both 5 and 8 exhibited in vitro affinity for the opiate receptor comparable to codeine and had analgesic properties in the writhing test.

Ro 21-7634, a new antiallergic agent with potent oral activity.

Ro 21-7634 was examined for oral antiallergic activity in two in vivo models commonly used to evaluate antiallergics. In the rat PCA test, this drug had an oral ID50 of 1.14 mg/kg and was found to be more potent than several other antiallergics including Disodium Cromoglycate (cromoglycate), Oxatomide, Doxanthrazole, Xanoxate, 2,6-bis (ethyoxyoxalylamino) pyridine, PRD-92-EA and M + B 22,948.