- Proposal for crystallization of 3-amino-4-halo-5-methylisoxazoles: An energetic and topological approach
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The supramolecular structure of 3-amino-4-halo-5-methylisoxazoles (halo = Cl, Br, and I) was investigated in order to suggest a route for crystallization of small molecules. The hierarchy of intermolecular interactions during the growth of the crystal was established by X-ray diffraction, 1H NMR titration, QTAIM analysis and quantum mechanical calculations. The relationship between QTAIM and energetic data was the fundamental innovation in this work. It allowed partitioning of the dimer interaction energy between interacting atoms. The partitioning shows the cooperation of the intermolecular interactions in the stabilization of the dimers and led to observation of the energetic consequences that small changes in the molecular structure of each compound may have on the crystal packing. The proposed route for the crystallization of the supramolecular cluster was based on the energetic hierarchy, in which the hydrogen bond is the strongest interaction and the first to form, and the π-interactions are weaker than the hydrogen bond and cannot compete with it. However, the π-interactions are responsible for the growth of the crystal, connecting the rising layers of the hydrogen bond dimers. The other interaction formed, the halogen bond, is too weak to compete with the other two interactions, but it is fundamental for linking the layer that leads to the final three-dimensional arrangement. Finally, a new way of understanding the crystallization process and the design of new materials is presented.
- Martins,Meyer,Tier,Longhi,Ducati,Bonacorso,Zanatta,Frizzo
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p. 7381 - 7391
(2015/10/05)
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- Regioselective, photochemical bromination of aromatic compounds using N-bromosuccinimide
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Regioselective nuclear bromination of aromatic compounds is investigated with N-bromosuccinimide as the brominating agent under UV irradiation to afford the corresponding brominated compounds. The reaction proceeds at ambient temperature (30 ± 2 °C) without any catalyst. In most of the reactions, regioselectively mono-brominated products are obtained in good to high yields. The conversion and selectivity for bromination depend on the nature of the substituent on the aromatic ring.
- Chhattise, Prakash K.,Ramaswamy,Waghmode, Suresh B.
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p. 189 - 194
(2008/03/30)
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- Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin
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Biphenylsulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, bicyclic or tricyclic carbon or heterocyclic ring biphenylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
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- N-aryl thienyl-, furyl-, and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin
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Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
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Page column 142
(2010/01/30)
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- N-(4-halo-isoxazolyl)-sulfonamides and derivatives thereof that modulate the activity of endothelin
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N-(4-halo-isoxazolyl)sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(4-halo-3-isoxazolyl)sulfonamides and N-(4-halo-5-isoxazolyl)benzenesulfonamides and methods for inhibiting the binding of an endothelin peptide to an endothelin receptor or increasing the activity of endothelin peptides by contacting the receptor with a sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
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- SULFONAMIDES AND DERIVATIVES THEREOF THAT MODULATE THE ACTIVITY OF ENDOTHELIN
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Sulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided. The sulfonamides have formula I: STR1 in which Ar 1 is a 3-or 5-isoxazolyl and Ar. sup.2 is selected from among alkyl, including straight and branched chains, aromatic rings, fused aromatic rings and heterocyclic rings, including 5-membered heterocycles with one, two or more heteroatoms and fused ring analogs thereof and 6-membered rings with one, two or more heteroatoms and fused ring analogs thereof. Ar 2 is preferably thiophenyl, furyl, pyrrolyl, naphthyl, and phenyl. Compounds in which Ar. sup.1 is a 4-halo-substituted isoxazole are more active than the corresponding alkyl-substituted compound and compounds in which Ar 1 is substituted at this position with a higher alkyl tend to exhibit greater affinity for ET B receptors than the corresponding lower alkyl-substituted compound.
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- N-(5-ISOXAZOLYL)BIPHENYLSULFONAMIDES, N-(3-ISOXAZOLYL)BIPHENYLSULFONAMIDES AND DERIVATIVES THEREOF THAT MODULATE THE ACTIVITY OF ENDOTHELIN
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N-(5-isoxazolyl)biphenylsulfonamides and N-(3-isoxazolyl) biphenylsulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(5-isoxazolyl)biphenylsulfonamides and N-(3-isoxazolyl)biphenylsulfonamides and methods for inhibiting the binding of an endothelin peptide to an endothelin receptor or increasing the activity of endothelin peptides by contacting the receptor with a sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
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- Synthesis of 4-Hydroxy-N--2-methyl-2H-1,2-benzothiazine-3-carboxamide 1,1-Dioxide and oxoacetic Acid. Major Metabolites of Isoxicam
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4-Hydroxy-N--2-methyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide (2), the major oxidative human metabolite of isoxicam (1), and oxoacetic acid (3), the major rat metabolite of isoxicam (1), were synthesized. 2 was synthesized by condensation of the known benzothiazine ester 8 with the isoxazolamine 9b. 9b was synthesized via a nine-step sequence starting with 5-methyl-3-isoxazolecarboxylic acid (14).NBS bromination of 14 gave 5-(bromomethyl)-3-isoxazolecarboxylic acid, which was coverted to the carbamate ester via a Curtius rearrangement of the acid azide.Displacement of bromine with silver acetate gave the acetoxy compound 21.Hydrolysis of 21 gave the unstable 3-isoxazolamine derivative 9a, which was converted to the OSiMe3 derivative 9b.The compound 3 was synthesized by reaction of ethyl oxalyl chloride with 5-methyl-3-isoxazolamine followed by base hydrolysis.
- Sircar, Jagadish C.,Capiris, Thomas,Bobovski, Thomas P.,Schwender, Charles F.
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p. 5723 - 5727
(2007/10/02)
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