- Conformational and crystal energetics of a polymorphic cyclized product of Napafenac: The Z′ and crystal stability correlation
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We report the single crystal diffraction study of a dimorphic 7-benzoyl-1,3-dihydroindol-2-one system and evaluate its stability relationships through thermal, grinding and slurry methods. Computational methods are invoked to understand the stability relationships. The form I crystallizes in the triclinic space group P1ˉ with two molecules in the asymmetric unit (Z′ = 2), whereas, form II crystallizes in the monoclinic space group P21/c with a single molecule in the asymmetric unit (Z′ = 1). The molecules exhibit subtle conformational variations along the bond connecting the phenyl and indole rings and adopt different crystal packing. While both polymorphs show similar amide dimer of NH?O interactions, they do differ significantly in the way the amide dimers are packed. The Differential Scanning Calorimetry (DSC), phase transformation studies and lattice energy calculations clearly established the greater stability of high Z′ form over low Z′ form, which contradicts the widely accepted notion that Z′ > 1 structures are usually kinetic (or metastable). The choice of two different orientations of phenyl rings in form I enforces shorter π?π interactions and additional CH?π contacts to result in the extra stabilization energy over form II crystal packing with a single conformer. The Z′ and stability correlation is established in 83 reported polymorphic systems which indicate that the number of stable crystal structures decrease as the Z′ value increases. However, the polymorphic systems with Z′ = 1 and 2 combinations are more frequently observed than any other combinations.
- Nanubolu, Jagadeesh Babu,Ravikumar, Krishnan,Sridhar, Balasubramanian,Sreedhar, Bojja
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- Preparation method of 7-benzoyl-1,3-indoline-2-ketone
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The invention discloses a preparation method of 7-benzoyl-1,3-indoline-2-ketone.The preparation method comprises the specific steps that 2-amino-3-benzoyl phenylacetamide is added in a reactor, an organic solvent is added until the solution is clear, a catalyst is added, reacting under temperature controlling is performed, and after reacting is completed, reduced-pressure concentration is performed to obtain 7-benzoyl-1,3-indoline-2-ketone.According to the method for preparing 7-benzoyl-1,3-indoline-2-ketone, the technology is stable, operation is easy, the yield is high, the purity is high, no harsh reaction condition is needed, the needed temperature and pressure are both within a conventional range, the adopted reagents are nontoxic, pollution is low, and the economical performance is achieved.
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Paragraph 0031; 0032
(2016/11/14)
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- Palladium-catalyzed direct addition of arylboronic acids to 2-aminobenzonitrile derivatives: Synthesis, biological evaluation and in silico analysis of 2-aminobenzophenones, 7-benzoyl-2-oxoindolines, and 7-benzoylindoles
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A palladium-catalyzed direct addition of arylboronic acids to unprotected 2-aminobenzonitriles has been developed, leading to a wide range of 2-aminobenzophenones with moderate to excellent yields. The transformation has broad scope and high functional group tolerance. Moreover, 2-oxoindoline-7-carbonitrile and indole-7-carbonitrile were applicable to this process for the construction of 7-benzoyl-2-oxoindolines and 7-benzoylindoles, respectively. Among the compounds examined, compound 4e possessed the most potent anticancer activity against H446 and HGC-27 in vitro, with IC50 values of 0.02 μmol L-1 and 0.09 μmol L-1, respectively, while compound 4a showed the best potent anticancer activity against SGC-7901 with an IC50 value of 0.01 μmol L-1. Furthermore, we also performed in silico molecular docking calculations to investigate the interaction mode and binding affinity between the examined compounds and their tubulin target. This journal is
- Chen, Jiuxi,Ye, Leping,Su, Weike
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supporting information
p. 8204 - 8211
(2015/01/08)
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- Antiinflammatory agents. 3. Synthesis and pharmacological evaluation of 2-amino-3-benzoylphenylacetic acid and analogues
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A series of substituted derivatives of 2-amino-3-benzoylphenylacetic acid (amfenac) has been synthesized and evaluated for antiinflammatory, analgesic, and cyclooxygenase inhibiting activity. Several derivatives including 4'-chloro, 4'-bromo and 5-chloro, 4'-bromo were more potent than indomethacin in these assays.
- Walsh,Moran,Shamblee,Uwaydah,Welstead Jr.,Sancilio,Dannenburg
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p. 1379 - 1388
(2007/10/02)
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- Antiinflammatory Agents. 2. Syntheses and Antiinflammatory Activity of Substituted 2-Aminophenylacetic Acid Derivatives
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Several substituted 2-aminophenylacetic acid derivatives were prepared and tested for in vitro prostaglandin synthetase inhibition and for in vivo antiinflammatory activity.The 2-amino substituent is beneficial to potency in the inhibition of prostaglandin synthetase for the 3-phenoxy, 4-phenyl, and 3-benzoyl series, but only 3-benzoyl series shows increased antiinflammatory potency in the in vivo assay.
- Walsh, David A.,Shamblee, Dwight A.,Welstead, William J.,Sancilio, Lawrence F.
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p. 446 - 451
(2007/10/02)
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- Intermediate and process for the preparation of 7-acylindolin-2-ones
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A novel process for the preparation of 7-acylindolin-2-ones of the formula: STR1 wherein R is hydrogen, halogen, lower alkyl, lower alkoxy, or trifluoromethyl; R1 is lower alkyl, alkylphenyl, cycloalkyl, or aryl; and R2 is hydrogen, lower alkyl or benzyl is provided. The compounds are useful as intermediates in the preparation of 2-amino-3-acylphenylacetic acid compounds which possess pharmaceutical properties.
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- 4-(5- And 7-)benzoylindolin-2-ones and pharmaceutical uses thereof
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Novel 4-(5- and 7-)benzoylindolin-2-ones of the formula: SPC1 Wherein R is hydrogen, lower-alkyl, or methylthio, R1 is hydrogen or lower-alkyl, R2 is lower-alkyl, lower-alkoxy, halogen, nitro or trifluoromethyl, R3 is hydrogen, halogen or lower-alkoxy, and n is 0, 1 or 2, are prepared by (a) acylation of indolin-2-one to give 5-benzoylindoline-2-one, (b) cyclization of 2-acetamido-3-benzoylphenylacetic acid or ethyl 2-acetamido-3-benzoylphenylacetate to give 7-benzoyindoline-2-one, or (c) by reacting aminobenzophenones with alkyl α(methylthio)acetates to give alkyl 2-amino-3-(5- or 6-)benzoyl-α-(methylthio)phenylacetates which are cyclized and demethylthiolated to 4-(5- and 7-)benzoylindolin-2-ones. The novel compounds possess anti-inflammatory activity and are intermediates for the preparation of 2-amino-3-(5- or 6-) benzoylphenylacetic acids which posess anti-inflammatory properties.
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