Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. V. Thienopyridazinone derivatives.

Synthesis and pharmacological evaluation of novel thienopyridazinones and related compounds are described. A thiophene ring was found to be able to replace the benzene ring of a phthalazinone without loss of biological activities. This observation supports our hypothesis that the benzene ring plays an important role in both thromboxane A2 (TXA2) synthetase-inhibitory and bronchodilatory activities. Further, it was shown that the carbonyl moiety of a phthalazinone is not necessary for these activities.

Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. VI. Indazole derivatives.

Synthesis and pharmacological evaluation of novel indazole derivatives are described. These compounds were found to exhibit both thromboxane A2 (TXA2) synthetase-inhibitory and bronchodilatory activities. This observation supports the idea that the partial structure of the 3-pyridyl and phenyl groups with a methylene insertion is an important component for well-balanced activities.

Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. IV. 2-[2-(1-Imidazolyl)ethyl]-4-(3-pyridyl)-1(2H)-phthalazinones.

Synthesis and pharmacological evaluation of several compounds related to 2-[2-(1-imidazolyl)ethyl]-4-(3-pyridyl)-1(2H)-phthalazinones are described. The phenyl moiety of the phthalazinone skeleton was found to play an important role in both thromboxane A2 synthetase-inhibitory and bronchodilatory activities. Further, the 3-pyridyl group at the 4-position was shown to be necessary for in vivo thromboxane A2 synthetase-inhibitory activity.

Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. III. 4-[2-(5-ethyl-2-thienyl)]-2'-[2-(1-imidazolyl)ethyl]-1(2H)- phthalazinones.

Synthesis and pharmacological evaluation of novel 4-[2-(5-ethyl-2-thienyl)]-2-[2-(1-imidazolyl)ethyl]-1(2H)-phthalazinone s are described. The phenyl moiety of the phthalazinone skeleton was found to play an important role in both thromboxane A2 synthetase-inhibitory and bronchodilatory activities.

Development of Babesia ovata in the ovary and eggs of the tick, Haemaphysalis longicornis.

The ovary and eggs of adult tick Haemaphysalis longicornis (H. longicornis) infected with Babesia ovata (B. ovata), were examined at regular intervals of time. As a result kinetes could be detected in the ovary for the first time 6 days after engorgement. The kinetics could be classified into three types on the basis of their morphological characteristics. On the 2nd day after oviposition, round-formed protozoa were found in the ooplasm of the egg. In 5 days after oviposition, these round-formed bodies were transformed into club-forms. On the 9th day after oviposition, the kinetes were observed in the ooplasm. Morphologically, it seemed possible that B. ovata is transmitted by eggs of the tick, H. longicornis.

Development of Babesia ovata in the midgut of the tick, Haemaphysalis longicornis.

Studies were made on the development of Babesia ovata in the midgut of the nymphal tick vector, Haemaphysalis longicornis. In 12 hr post-repletion, merozoites were observed outside of erythrocytes infected with B. ovata in the contents of the midgut of the tick. After that, these merozoites were transformed into ring-forms which were comparatively large ring 2-3 microns in diameter. Within 48-72 hr post-repletion, ring-form protozoa developed into spherical form 4-5 microns in diameter. Within 3-4 days post-repletion, fission-forms were transformed into fission-bodies 2-3 microns in diameter. Within 4-6 days post-repletion, fission-bodies developed into bizarre-forms 6-7 microns in diameter. At this time, elongated form protozoa which were considered as microgametes, 6-8 microns in length, are also seen. Within 6-8 days post-repletion, round-formed protozoa which were considered as zygotes in 9-10 microns in diameter were observed in the gut. About 10 days after repletion, those round-formed protozoa were transformed into vermicule-formed and round-formed protozoa, 13-15 microns in length, appeared again in the gut epithelial cells.