Abstract
Unlike the oxetane ring, which, as evidenced by numerous studies, is known to play an
increasingly important role in medicinal chemistry, the thietane ring has thus far received comparatively
limited attention. Nonetheless, a growing number of reports now indicate that this 4-
membered ring heterocycle may provide opportunities in analog design. In the present review article,
we discuss the possible use and utility of the thietane fragment in medicinal chemistry and provide
an overview of its properties and recent applications with a focus on isosteric replacements.
Keywords:
Thietanes derivatives, Medicinal chemistry, Oxetane ring, MMP, Arachidonic acid, Heterocycles.
Graphical Abstract
[10]
Bevan, J.W.; Legon, A.C.; Millen, D.J. Tilts, bends, and twists of
methylene groups in four-membered rings. Evidence from the microwave
spectrum of trimethylene sulphoxide. J. Chem. Soc.,
Chem. Comm., 1974, 659-660.
[12]
Barlow, J.H.; Hall, R.; Russell, D.R.; Smith, D.J.H. Stereochemical assignments of 3-substited thietan-1-oxides. The crystal structures of cis- and trans-3-p-bromophenylthietan-1-oxides. J. Chem. Soc., Chem. Comm, 1975, 133-134.
[13]
Chiang, J.F. Structure of 3-Bromo- &6-thietane 1,1-Dioxide, C3H3BrO2S. Acta Crystallogr., 1983, C39, 737-738.
[15]
Ziegler, M.L.; Weib, J.; Schildknecht, H.; Grund, N.; Sasse, H-E. Die kristall- und molekulstruktur von 2,2-dimethylthietan- 1,1-dioxid. Justus Liebigs Ann. Chem., 1972, 1702-1709.
[18]
Block, E. Comprehensive Heterocyclic Chemistry; Katritzky, A.R; Rees, C.W., Ed.; Elsevier, 1984, p. 7.
[38]
Hamano, S.; Komatsu, H.; Hiraku, S.; Ujiie, A. Role of thromboxane A2 (TXA2) in the phospholipid metabolism in rabbit platelets. Nihon Kessen Shiketsu Gakkai shi, 1986, 17, 315-321.
[99]
Kung, P.P.; Bingham, P.; Brooun, A.; Collins, M.; Deng, Y.L.; Dinh, D.; Fan, C.; Gajiwala, K.S.; Grantner, R.; Gukasyan, H.J.; Hu, W.; Huang, B.; Kania, R.; Kephart, S.E.; Krivacic, C.; Kumpf, R.A.; Khamphavong, P.; Kraus, M.; Liu, W.; Maegley, K.A.; Nguyen, L.; Ren, S.; Richter, D.; Rollins, R.A.; Sach, N.; Sharma, S.; Sherrill, J.; Spangler, J.; Stewart, A.E.; Sutton, S.; Uryu, S.; Verhelle, D.; Wang, H.; Wang, S.; Wythes, M.; Xin, S.; Yamazaki, S.; Zhu, H.; Zhu, J.; Zehnder, L.; Edwards, M. Optimization of orally bioavailable enhancer of zeste homolog 2 (ezh2) inhibitors using ligand and property-based design strategies: identification of development candidate (R)-5,8-dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497).
J. Med. Chem., 2018,
61(3), 650-665.
[
http://dx.doi.org/10.1021/acs.jmedchem.7b01375] [PMID:
29211475]