基于单一合成序列的针对两个不同生物靶标家族的纳摩尔级抑制剂：组合文库设计的下一步？

Nanomolar Inhibitors for Two Distinct Biological Target Families from a Single Synthetic Sequence: A Next Step in Combinatorial Library Design?

作者信息

Burns Christopher J, Groneberg Robert D, Salvino Joseph M, McGeehan Gerard, Condon Stephen M, Morris Robert, Morrissette Matthew, Mathew Rose, Darnbrough Shelley, Neuenschwander Kent, Scotese Anthony, Djuric Stevan W, Ullrich John, Labaudiniere Richard

机构信息

Rhône-Poulenc Rorer, 500 Arcola Rd., Collegeville, PA 19426 (USA), Fax: (+1) 610-454-3311.

出版信息

Angew Chem Int Ed Engl. 1998 Nov 2;37(20):2848-2850. doi: 10.1002/(SICI)1521-3773(19981102)37:20<2848::AID-ANIE2848>3.0.CO;2-C.

DOI:10.1002/(SICI)1521-3773(19981102)37:20<2848::AID-ANIE2848>3.0.CO;2-C

PMID:29711099

Abstract

One common synthetic route creates small-molecule libraries directed toward two functionally distinct target families. The novel structural template 1 can independently display the necessary pharmacophore patterns for inhibition of members of two different biomolecular target families, the matrix metalloproteinases (MMPs) or the phosphodiesterases (PDEs). The incorporation of multiple target family directed design elements into combinatorial library design could help expedite the pharmaceutical lead discovery process. Z=OR' (PDE4), H (MMPs).

摘要

一种常见的合成路线可生成针对两个功能不同的靶标家族的小分子文库。新型结构模板1能够独立展现出抑制两种不同生物分子靶标家族（基质金属蛋白酶（MMP）或磷酸二酯酶（PDE））成员所需的药效团模式。将多个靶向家族的设计元素纳入组合文库设计中有助于加快药物先导物的发现过程。Z = OR'（PDE4），H（MMP）。