- Direct cycle between co-product and reactant: An approach to improve the atom economy and its application in the synthesis and protection of primary amines
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Two important goals of green chemistry are to maximize the efficiency of reactants and to minimize the production of waste. In this study, a novel approach to improve the atom economy of a chemical process was developed by incorporating a direct cycle between a co-product and a reactant of the same reaction. To demonstrate this concept, recoverable 3,4-diphenylmaleic anhydride (1) was designed and used for the atom-economical synthesis of aliphatic primary amines from aqueous ammonia. In each individual cycle, only ammonia and alkyl halide were consumed, and 1 was recovered in nearly a quantitative yield. In this approach for developing atom-economical protecting agents, 1 showed good performance as a recoverable protecting agent for primary amines. The broad substrate scope, good tolerance to various reaction conditions, and high reaction and recovery rates make 1 a valuable complement to conventional primary amine protecting agents.
- Guan, Qi,Jiang, Mingyang,Wu, Junhui,Zhai, Yanpeng,Wu, Yue,Bao, Kai,Zhang, Weige
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supporting information
p. 5794 - 5799
(2016/11/06)
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- O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1
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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.
- 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.
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p. 564 - 576
(2016/01/09)
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- CONTROLLED RELEASE OF ACTIVE COMPOUNDS FROM DYNAMIC MIXTURES
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The present invention relates to a dynamic mixture in the form of a dynamic mixture obtained by reacting together, in the presence of water, at least one O-substituted hydroxylamine or S-substituted thiohydroxylamine derivative with at least one perfuming
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- 2-chloro-N6 -substituted adenosines, their pharmaceutical compositions, and activity in treating ischemias
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Adenosine compounds having the following structure STR1 wherein X is halogen, perhalomethyl, acetamido, cyano, C 1-6 -alkoxy, C 1-6 -alkylthio or C 1-6 -alkylamino; andR 1 is --NR 2 R 3 or YR 4, wherein Y is oxygen or sulfur;R 2 is phenyl, C 1-6 -alkyl or
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- Symmetrical O-substituted dioximes of benzo-fused β-diketocyclo-alkylenes, the processes for their preparation and their application as drugs
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Drugs with high anticonvulsant and analgesic activities constituted by symmetrical β-dialkoxyiminocycloalklene derivatives in which the imine double bonds are conjugated with the cyclic double bond or bonds belonging to one or more fused benzene rings. They correspond to the general formula I: STR1
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