Journal article
Evaluation of Oxetan-3-ol, Thietan-3-ol, and Derivatives Thereof as Bioisosteres of the Carboxylic Acid Functional Group
P Lassalas, K Oukoloff, V Makani, M James, V Tran, Y Yao, L Huang, K Vijayendran, L Monti, JQ Trojanowski, VMY Lee, MC Kozlowski, AB Smith, KR Brunden, C Ballatore
ACS Medicinal Chemistry Letters | Published : 2017
Abstract
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 isoster..
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Awarded by National Science Foundation
Funding Acknowledgements
Financial support for this work has been provided in part by the NIH/NIA (Grant AG044332-01), the NSF Grant CHE-0840438 (X-ray facility), the Woods Charitable Foundation, and the Cenci Bolognetti Foundation (LM).