基于 2-(2-氨噻唑-4-基)吡咯烷的酒石酸盐双酰胺作为强效、选择性和口服生物利用度的 TACE 抑制剂。
2-(2-Aminothiazol-4-yl)pyrrolidine-based tartrate diamides as potent, selective and orally bioavailable TACE inhibitors.
机构信息
Department of Chemistry, Merck Research Laboratories, 320 Bent Street, Cambridge, MA 02141, USA.
出版信息
Bioorg Med Chem Lett. 2011 May 15;21(10):3172-6. doi: 10.1016/j.bmcl.2011.01.002. Epub 2011 Jan 6.
TNF-α converting enzyme (TACE) inhibitors are promising agents to treat inflammatory disorders and cancer. We have investigated novel tartrate diamide TACE inhibitors where the tartrate core binds to zinc in a unique tridentate fashion. Incorporating (R)-2-(2-N-alkylaminothiazol-4-yl)pyrrolidines into the left hand side amide of the tartrate scaffold led to the discovery of potent and selective TACE inhibitors, some of which exhibited good rat oral bioavailability.
TNF-α 转化酶（TACE）抑制剂是治疗炎症性疾病和癌症的有前途的药物。我们研究了新型的酒石酸二酰胺 TACE 抑制剂，其中酒石酸核心以独特的三齿方式结合锌。将（R）-2-（2-N-烷氨基噻唑-4-基）吡咯烷引入酒石酸支架的左手侧酰胺中，发现了有效的、选择性的 TACE 抑制剂，其中一些具有良好的大鼠口服生物利用度。
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