The　inhibition　of　11β-hydroxysteroid　dehydrogenase　type　1　(11β-HSD1)　has　demonstrated　potential　for　the　treatment　of　various　components　of　metabolic　syndrome.　In　this　study,　a　series　of　1,4-diaryl-1,4-dihydropyrazines　were　designed　as　inhibitors　of　11β-HSD1　based　on　the　structure-activity　relationship　of　known　11β-HSD1　inhibitors　through　docking　simulations.　The　docking　simulation　results　supported　the　initial　pharmacophore　hypothesis:　the　docking　results　of　the　known　inhibitors　with　11β-HSD1　suggested　a　similar　interaction　of　1,4-diaryl-1,4-dihydropyrazines　with　the　catalytic　site　of　11β-HSD1.　Twelve　of　these　compounds　were　synthesized　through　the　cyclization　of　N,N-dialkylanilines　with　anilines,　and　their　structures　were　determined　by　(1)H-NMR,　(13)C-NMR,　high　resolution　(HR)-MS,　and　single-crystal　X-ray　diffraction.　The　inhibitory　activities　of　these　compounds　against　human　11β-HSD1　were　investigated　in　vitro　through　a　scintillation　proximity　assay　using　microsomes　containing　11β-HSD1.