Benzoxazole Derivatives as Novel 5-HT₃Receptor Partial Agonists in the Gut

Abstract

A series of benzoxazoles with a nitrogen-containing heterocyclic substituent at the 2-position was prepared and evaluated for 5-HT3 partial agonist activity on isolated guinea pig ileum. The nature of the substituent at the 5-position of the benzoxazole ring affected the potency for the 5-HT3 receptor, and the 5-chloro derivatives showed increased potency and lowered intrinsic activity. 5-Chloro-7-methyl-2-(4-methyl-1-homopiperazinyl)benzoxazole (6v) exhibited a high binding affinity in the same range as that of the 5-HT3 antagonist granisetron, and its intrinsic activity was 12% of that of 5-HT. Compound 6v inhibited 5-HT-evoked diarrhea but did not prolong the transition time of glass beads in the normal distal colon even at a dose of 100 times the ED50 for diarrhea inhibition in mice. Compounds of this type are expected to be effective for the treatment of irritable bowel syndrome without the side effect of constipation.

N,N-Dialkyl-N′-Chlorosulfonyl Chloroformamidines in Heterocyclic Synthesis. Part VII 4-Dialkylamino[1,2,3,5]Benzoxathiadiazepine Dioxides and 4-Dialkylamino-[2,1,3,5]Benzothiatriazepine Dioxides

“…Upon chromatographic purification of the residue from evaporation of the mother liquor from isolation of 3b, the only clearly identifiable component was 2-piperidin-1-ylbenzoxazole, [9,10] produced in low yield.…”

An Update on the Synthesis of Benzoxazoles

“…Piperidine-4-carboxylic acid and o-aminophenol were heated with polyphosphoric acid to afford [31] (61).…”

The synthesis of a series of adenosine A3receptor agonists

“…As dichloromethylene(diethyl)ammonium chloride was not commercially available at the time, the original synthesis had to be modified. Therefore, following the literature precedent, the aminophenol 23 was converted into the thione 28 using carbon disulfide and potassium hydroxide in ethanol, 16 the product being identified as the thione tautomer by analogy with the literature. 17 The ARTICLE attempted direct conversion of the thione 28 into the corresponding diethylamino-oxazole using diethylamine delivered unchanged starting material, perhaps because of the volatility of diethylamine.…”