4732-11-0Relevant articles and documents
O-Isocyanates as Uncharged 1,3-Dipole Equivalents in [3+2] Cycloadditions
Allen, Meredith A.,Beauchemin, André M.,Ivanovich, Ryan A.
supporting information, p. 23188 - 23197 (2020/10/12)
1,3-Dipoles are commonly used in [3+2] cycloadditions, whereas isoelectronic uncharged dipole variants remain underdeveloped. In contrast to conventional 1,3-dipoles, uncharged dipole equivalents form zwitterionic cycloadducts, which can be exploited to build further molecular complexity. In this work, the first cycloadditions of oxygen-substituted isocyanates (O-isocyanates) were studied experimentally and by DFT calculations. This unique cycloaddition strategy provides access to a novel class of heterocycle aza-oxonium ylides through intramolecular and intermolecular cycloadditions with alkenes. This allowed a systematic study of the reactivity of the transient aza-oxonium ylide intermediate, which can undergo N?O bond cleavage followed by nitrene C?H insertion, and the formation of β-lactams or isoxazolidinones upon varying the structure of the alkene or O-isocyanate reagents.
O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1
Malachowski, William P.,Winters, Maria,DuHadaway, James B.,Lewis-Ballester, Ariel,Badir, Shorouk,Wai, Jenny,Rahman, Maisha,Sheikh, Eesha,LaLonde, Judith M.,Yeh, Syun-Ru,Prendergast, George C.,Muller, Alexander J.
, p. 564 - 576 (2016/01/09)
Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a potent sub-micromolar inhibitor of IDO1. Structure-activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications.
3,6-Bicyclolides
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Page/Page column 47, (2008/06/13)
The present invention discloses compounds of formula (I) or pharmaceutically acceptable salts, esters, or prodrugs thereof: which exhibit antibacterial properties. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject in need of antibiotic treatment. The invention also relates to methods of treating a bacterial infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The invention further includes process by which to make the compounds of the present invention.