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Two subseries of nonquaternized (5a-10a) and quaternized derivatives (5b-10b) related to oxotremorine and oxotremorine-M were synthesized and tested. The agonist potency at the muscarinic receptor subtypes of the new compounds was estimated in three classical in vitro functional assays: M1 rabbit vas deferens, M2 guinea pig left atrium and M3 guinea pig ileum. In addition, the occurrence of central muscarinic effects was evaluated as tremorigenic activity after intraperitoneal administration in mice. In in vitro tests a nonselective muscarinic activity was exhibited by all the derivatives with potencies values that, in some instances, surpassed those of the reference compounds (i.e. 8b). Functional selectivity was evidenced only for the oxotremorine-like derivative 9a, which behaved as a mixed M3 -agonist/M1 -antagonist (pD2 =5.85; pA2 =4.76, respectively). In in vivo tests non- quaternary compounds were able to evoke central muscarinic effects, with a potency order parallel to that observed in vitro. (C) 1999 Elsevier Science Ltd. All rights reserved.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H1232NO – PubChem

 

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A novel series of muscarinic receptor ligands of the hexamethonio-type was prepared which contained, on one side, the phthalimidopropane or 1,8-naphthalimido-2,2-dimethylpropane moiety typical for subtype selective allosteric antagonists and, on the other, the acetylenic fragment typical for the nonselective orthosteric muscarinic agonists oxotremorine, oxotremorine-M, and related muscarinic agonists. Binding experiments in M2 receptors using [3H]N-methylscopolamine as an orthosteric probe proved an allosteric action of both groups of hybrids, 7a-10a and 8b-10b. The difference in activity between a-group and b-group hybrids corresponded with the activity difference between the allosteric parent compounds. In M1-M 3 muscarinic isolated organ preparations, most of the hybrids behaved as subtype selective antagonists. [35S]GTPgammaS binding assays using human M2 receptors overexpressed in CHO cells revealed that a weak intrinsic efficacy was preserved in 8b-10b. Thus, attaching muscarinic allosteric antagonist moieties to orthosteric muscarinic agonists may lead to hybrid compounds in which functions of both components are mixed.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H1234NO – PubChem

 

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This review is focused on the synthesis of isoxazolidines as the core of biologically active compounds having anti-cancer, antiviral, antibacterial and anti-inflammatory properties. The isoxazolidine ring, as mimetic of ribose, has been principally synthesized with high regio-, stereo- and enantioselectivity, applying the methodology of 1,3-dipolar cycloaddition, involving nitrones and alkenes as dipoles and dipolarophiles, respectively. The easy accessibility of this ring by this approach, then, makes this heterocycle, particularly suitable for the synthesis of small molecules useful in the design of new and modified drugs.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H1230NO – PubChem

 

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The pyrimidine nucleus is a versatile core in the development of antiretroviral agents. Onthis basis, a series of pyrimidine-2,4-diones linked to an isoxazolidine nucleus have been synthesized and tested as nucleoside analogs, endowed with potential anti-HIV (human immunodeficiency virus) activity. Compounds 6a-c, characterized by the presence of an ethereal group at C-3, show HIV reverse transcriptase (RT) inhibitor activity in the nanomolar range as well as HIV-infection inhibitor activity in the low micromolar with no toxicity. In the same context, compound 7b shows only a negligible inhibition of RT HIV.

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Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H1245NO – PubChem

 

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Several grass and broadleaf weed species around the world have evolved multiple-herbicide resistance at alarmingly increasing rates. Research on the biochemical and molecular resistance mechanisms of multiple-resistant weed populations indicate a prevalence of herbicide metabolism catalyzed by enzyme systems such as cytochrome P450 monooxygenases and glutathione S-transferases and, to a lesser extent, by glucosyl transferases. A symposium was conducted to gain an understanding of the current state of research on metabolic resistance mechanisms in weed species that pose major management problems around the world. These topics, as well as future directions of investigations that were identified in the symposium, are summarized herein. In addition, the latest information on selected topics such as the role of safeners in inducing crop tolerance to herbicides, selectivity to clomazone, glyphosate metabolism in crops and weeds, and bioactivation of natural molecules is reviewed.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H1240NO – PubChem

 

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The high selectivity of the Cp2ZrHCl reducing agent for imides: A combined experimental and theoretical study on gamma-lactam and isoxazolidinone derivatives

Selective reductions of semicyclic imides either to hemiaminals (endo carbonyl reduction) or to aldehydes and amines (exo carbonyl reduction) in high yields by Schwartz’s reagent (Cp2ZrHCl) are reported. Mechanistic aspects of these reactions have been investigated at the DFT ab initio level with consideration of implicit solvent effects and thermal and pressure corrections to 298 K/1 atm. The reactions proceed from the reagents to very stable final Zr-oxo intermediates through the formation of sigma complexes and subsequent four-center transition state structures (1,2-migratory insertion). The energetic barriers for the insertion steps depend strongly on the natures of the ancillary groups at the reducing carbonyl groups. N-Carbamoyl groups are reduced to hemiaminals whereas N-acyl groups react at the exo carbonyl groups. The absence of the second carbonyl group in the simple N-methyl-2-pyrrolidone (less oxidized system) strongly reduces the thermodynamic drive for the formation of the metallocene oxo intermediate and allows an explanation of the remarkable chemoselectivity of the hydrozirconation. The zirconocene-oxo intermediates hydrolyze quickly throughout an ionic mechanism in which water molecules strongly assist the process by stabilizing ion pair separation. The computational results are consistent with a large set of experimental data on reduction of gamma-lactam and isoxazolidinone derivatives under mild conditions. They provide a way to explain and predict the relative importance of the two competitive endo/exo reduction channels of semicyclic imides by considering the electronic and steric features of substituents. Semicyclic imides such as gamma-lactam and isoxazolidinone derivatives are efficiently and selectivity reduced by the Cp2ZrHCl agent. The energetic reaction pathways for endo and exo attack, computed at the DFT level including thermal effects, allow an exhaustive interpretation of current and previously reported experimental data. Copyright

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Oxazolidine – Wikipedia,
Oxazolidine | C3H1237NO – PubChem

 

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A Convenient and Concise Metal-Free Approach to Functionalized Bicyclic Pyrimidinones from Oxazine-2,6-diones

The synthesis of previously unreported pyrazolo-pyrimidinones and isoxazolo-pyrimidinones are achieved via metal-free coupling of oxazine-2,6-diones with pyrazolidinone and isoxazolidinone, respectively. The synthesis provides easy access to a variety of novel 2-dimensional building blocks that can be derivatized to generate a range of drug- and agro-like molecules.

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Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H1248NO – PubChem

 

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Preparation of N- and S-1,2-ethylenically unsaturated organic compounds

The invention is a process for the preparation of a N- or S-1,2-ethylenically unsaturated organic compound which comprises (a) contacting a N- or S-silylated organic compound with an aldehyde, wherein the aldehyde has a hydrogen atom bonded to the carbon adjacent to the carbonyl moiety, at elevated temperatures under conditions such that a N- or S-1-siloxyalkyl-substituted organic compound is prepared; and (b) pyrolyzing the N- or S-1-siloxyalkyl-substituted organic compound under conditions such that the siloxy moiety is elminated to prepare a N- or S-1,2-ethylenically unsaturated compound.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H1227NO – PubChem

 

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Structure-function studies of acinetobactin analogs

Pathogenic Acinetobacter baumannii excrete the siderophore pre-acinetobactin as an iron-scavenging virulence factor. Pre-acinetobactin is a 2,3-dihydroxy-phenyl oxazoline that undergoes pH-dependent isomerization to the isooxazolidinone form acinetobactin in order to expand the pH range for iron acquisition by A. baumannii. In this study we establish important structure-function relationships for the kinetics of isomerization, iron(iii) binding, and siderophore utilization by A. baumannii. We showed that electronic properties of the phenyl oxazoline influence isomerization kinetics and iron(iii) binding. We found that iron(iii) chelation was directly correlated with A. baumannii utilization. Our studies provide important structural and mechanistic insight for understanding how pathogenic A. baumannii uses pre-acinetobactin as a 2-for-1 iron-scavenging siderophore virulence factor.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H1247NO – PubChem

 

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Design, synthesis and antitumor study of a series of N-Cyclic sulfamoylaminoethyl substituted 1,2,5-oxadiazol-3-amines as new indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors

Indoleamine 2, 3-dioxygenase 1 (IDO1) plays a key role in tryptophan catabolism which is an important mechanism in immune tolerance. The small molecule epacadostat is the most advanced IDO1 inhibitor, but its phase III trials as a single agent or in combinations with PD-1 antibody failed to show appreciable objective responses. To gain more insight on the antitumor efficacy of IDO1 inhibitors, we have designed a series of analogues of epacadostat by incorporating a cyclic aminosulfonamide moiety as the sidechain capping functionality. Compound 5a was found to display significant potency against recombinant hIDO1 and hIDO1 expressed HEK293 cancer cells. This compound has improved physico-chemical properties, acceptable PK parameters as well as optimal cardiac safety. Similar to epacadostat, 5a is ineffective as single agent in the CT-26 syngeneic xenograft model, however, the combination of 5a with PD-1 antibody showed both elevated tumor growth inhibition and prolonged median life span.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H1229NO – PubChem