Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model.

中文翻译：

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磺胺嘧啶作为有效的RORγ反向激动剂

高亲脂性阻碍了鉴定合适的RORγ反向激动剂作为临床候选物的进展，而高亲脂性似乎是对该核受体具有高效力所必需的。在这种情况下，我们决定专注于取代在已知调节剂上发现的羟甲基基团，以确定在该位置是否可以容许更多的极性。本文介绍了该部分置换的SAR，从而鉴定了亚砜亚胺衍生物作为在体内小鼠咪喹莫特牛皮癣模型中具有药理活性的强效调节剂。