No abstract

Several 3-(sulfamoylmethyl)-1,2-benzisoxazole derivatives were synthesized from 3-(bromomethyl)-1,2-benzisoxazole by the reaction with sodium bisulfite followed by chlorination and amination. Some of them displayed marked anticonvulsant activity in mice. The introduction of a halogen atom to the 5 position of the benzisoxazole ring caused increased activity and neurotoxicity; the substitution of a sulfamoyl group caused decreased activity. The activity of monoalkylated compounds might be the result of biotransformation. Among these compounds, 3-(sulfamoylmethyl)-1,2-benzisoxazole (1a) was thought to be the most promising as an anticonvulsant from the ratio of NTD50 and ED50.

Abstract. Emerging aquatic insects from streams are important food sources for riparian predators, yet their availability is seasonally limited. Spatial heterogeneity in stream water temperature was found to spatially desynchronize the emergence timing of aquatic insects, and prolong their flight period, potentially enhancing consumer growth. While a mayfly Ephemerella maculata emergence lasted for 12-22 d in local sites along a river, mayflies emerged 19 days earlier from warmer than cooler sites. Therefore, the overall emergence of E. maculata from the river lasted for 37 d, and adult swarms were observed over that same period in an adjacent reproductive habitat. A feeding experiment with the riparian spider Tetragnatha versicolor showed that a prolonged subsidy, as would occur in a heterogeneous river, led to higher juvenile growth than a synchronous pulsed subsidy of equal total biomass, as would typify a more homogeneous river. Since larger female adult spiders produce more eggs, spiders that received prolonged subsidy as juveniles should achieve higher fecundity. Restoring spatial heterogeneity in streams may benefit not only stream communities but also riparian predators.

Animal migrations can link ecosystems across space. We discovered an aquatic insect that migrates between a river mainstem and its tributaries, and provides an important trophic subsidy for tributary predators. A mayfly, Ephemerella maculata, rears in a warm, sunlit productive river mainstem, then migrates as adults to cool, shaded unproductive tributaries where they oviposit and die. This migration tripled insect flux into a tributary for 1 month in summer. A manipulative field experiment showed that this E. maculata subsidy nearly tripled the growth of the young of the year steelhead trout (Oncorhynchus mykiss) in the recipient tributary over the summer months, and was more important than terrestrial invertebrate subsidies, which have been considered the primary food source for predators in small, forested creeks. By delivering food subsidies from productive but warming river mainstems to cool but food-limited tributaries, aquatic insect migrations could enhance resilience to cool-water predators in warming river networks.

10,ll-Dihydro-ll-oxodibenz[6,/]oxepinacetic acids and related compounds were synthesized as potential antiinflammatory agents. Among them,/]oxepin-2-yl)propionic acid (16b) and its thiepin analogue (16c) showed excellent antipyretic activity together with potent antiinflammatory and analgesic properties in biological tests. Structure-activity relationships are discussed, In recent years a number of arylacetic acid derivatives have been reported to possess potent antiinflammatory activity in animal tests,2 and several of them have been clinically used.3 Shen4 has proposed a hypothetical antiinflammatory receptor site for indomethacin-type nonsteroidal agents, and for optimal receptor interaction, the two aromatic rings in a molecule should be out of plane. We, therefore, carried out the synthesis of the arylacetic acid derivatives containing tricyclic systems, such as dibenz[b,/]oxepin and dibenzo[b,/]thiepin, their 10,11-dihydro-11-oxo and 10,11-dihydro-ll-hydroxy analogues, and 10.11-dihydro-ll-oxodibenz[6,/][l,4]oxazepin, in which the two benzene rings are held in a noncoplanar orientation by the two-atom bridge, and subjected them to biological tests. Consequently, it was found that 2-(8-methyl-10.11-dihydro-ll-oxodibenz[i>,/]oxepin-2-yl)propionic acid (16b) and its thiepin analogue (16c) were highly active as o 16b, X = O c, X= S antiinflammatory, analgesic, and antipyretic agents. Based on these data, they have been selected for further study.Recently, the Nippon Chemiphar group has reported an analogous study in a patent5 independently of our work.6Chemistry. Dibenz[6,/]oxepinacetic acid derivatives (8-10) have been synthesized by the route shown in Scheme I. Ullmann reaction between 2-iodobenzoic acids 1 and ethyl hydroxybenzoates 2 gave the diphenyl ethers 3, which were reduced with lithium aluminum hydride to afford the diols 4. On chlorination, followed by reaction with sodium cyanide, 4 gave the bis(cyanomethyl) derivatives 6. Hydrolysis of 6 and subsequent cyclization with(1)