Evaluation of Oxetan-3-ol, Thietan-3-ol, and Derivatives Thereof as Bioisosteres of the Carboxylic Acid Functional Group

被引：34

作者：

Lassalas, Pierrik ^{[1
]}

Oukoloff, Killian ^{[2
]}

Makani, Vishruti ^{[3
]}

James, Michael ^{[3
]}

Van Tran ^{[1
]}

Yao, Yuemang ^{[3
]}

Huang, Longchuan ^{[1
]}

Vijayendran, Krishna ^{[1
]}

Monti, Ludovica ^{[2
]}

Trojanowski, John Q. ^{[3
]}

Lee, Virginia M. -Y. ^{[3
]}

Kozlowski, Marisa C. ^{[1
]}

Smith, Amos B., III ^{[1
]}

Brunden, Kurt R. ^{[3
]}

Ballatore, Carlo ^{[2
]}

机构：

[1] Univ Penn, Dept Chem, Sch Arts & Sci, Philadelphia, PA 19104 USA

[2] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, 9500 Gilman Dr, La Jolla, CA 92093 USA

[3] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2017年 / 8卷 / 08期

关键词：

Oxetan-3-ol; thietan-3-ol; carboxylic acid bioisostere; cyclooxygenase; lipoxygenase; dual inhibitors; MEDICINAL CHEMISTRY; DRUG DISCOVERY; RECEPTOR ANTAGONISTS; DUAL INHIBITORS; OXETANES; DESIGN; CYCLOPENTANE-1,3-DIONE; SULFONIMIDAMIDES; ISOSTERES; PEPTIDES;

D O I：

10.1021/acsmedchemlett.7b00212

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The oxetane ring serves as an isostere of the carbonyl moiety, suggesting that oxetan-3-ol may be considered as a potential surrogate of the carboxylic acid functional group. To investigate this structural unit, as well as thietan-3-ol and the corresponding sulfoxide and sulfone derivatives, as potential carboxylic acid bioisosteres, a set of model compounds has been designed, synthesized, and evaluated for physicochemical properties. Similar derivatives of the cyclooxygenase inhibitor, ibuprofen, were also synthesized and evaluated for inhibition of eicosanoid biosynthesis in vitro. Collectively, the data suggest that oxetan-3-ol, thietan-3-ol, and related structures hold promise as isosteric replacements of the carboxylic acid moiety.

引用

页码：864 / 868

页数：5

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