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These data suggest a novel molecular mechanism of action for semagacestat via modest GHS-R1a receptor activation. Studies focusing on the relative functional consequence of such effects in vivo are now warranted.

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The palladium-catalyzed decarboxylative cross-coupling of aminothiophene carboxylate and 1-bromo-4-chlorobenzene to produce 3-amino-2-(4-chlorophenyl)thiophene (2) is described. The cross-coupling proceeds under relatively mild conditions using catalytic Pd(0) and TBAB. Through use of a mixed-solvent system of DMF and NMP, it was possible to operate the cross-coupling system at 80 °C. An assessment of carbon dioxide liberation, which provides insight into the reaction operating parameters, is also discussed.