Discovery of a highly orally bioavailable c-5-[6-(4-Methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane-r-2-carboxylic acid as a potent hypoglycemic and hypolipidemic agent

Pingali, Harikishore; Jain, Mukul; Shah, Shailesh R.; Basu, Sujay; Makadia, Pankaj; Goswami, Amitgiri; Zaware, Pandurang; Patil, Pravin; Godha, Atul K.; Giri, Suresh; Goel, Ashish; Patel, Mehul S.; Patel, Harilal; Patel, Pankaj

doi:10.1016/j.bmcl.2008.08.112

Cited by 12 publications

(4 citation statements)

References 23 publications

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“…N -alkylation of the commercially available key intermediate 12 with custom synthesized [4-(4-fluorophenyl)butyl] methanesulfonate afforded intermediate 13 in 49% yield. Further treatment with BBr 3 yielded phenolic reference compound 14 (PF-NB1) in 61% yield.…”

Section: Resultsmentioning

confidence: 99%

Structure–Affinity Relationships of 2,3,4,5-Tetrahydro-1H-3-benzazepine and 6,7,8,9-Tetrahydro-5H-benzo[7]annulen-7-amine Analogues and the Discovery of a Radiofluorinated 2,3,4,5-Tetrahydro-1H-3-benzazepine Congener for Imaging GluN2B Subunit-Containing N-Methyl-d-aspartate Receptors

et al. 2019

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Aspiring to develop a positron emission tomography (PET) imaging agent for the GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), a key therapeutic target for drug development toward several neurological disorders, we synthesized a series of 2,3,4,5-tetrahydro-1H-3-benzazepine and 6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amine analogues. After in vitro testing via competition binding assay and autoradiography, [18F]PF-NB1 emerged as the best performing tracer with respect to specificity and selectivity over σ1 and σ2 receptors and was thus selected for further in vivo evaluation. Copper-mediated radiofluorination was accomplished in good radiochemical yields and high molar activities. Extensive in vivo characterization was performed in Wistar rats comprising PET imaging, biodistribution, receptor occupancy, and metabolites studies. [18F]PF-NB1 binding was selective to GluN2B-rich forebrain regions and was specifically blocked by the GluN2B antagonist, CP-101,606, in a dose-dependent manner with no brain radiometabolites. [18F]PF-NB1 is a promising fluorine-18 PET tracer for imaging the GluN2B subunits of the NMDAR and has utility for receptor occupancy studies.

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Section: Resultsmentioning

confidence: 99%

Structure–Affinity Relationships of 2,3,4,5-Tetrahydro-1H-3-benzazepine and 6,7,8,9-Tetrahydro-5H-benzo[7]annulen-7-amine Analogues and the Discovery of a Radiofluorinated 2,3,4,5-Tetrahydro-1H-3-benzazepine Congener for Imaging GluN2B Subunit-Containing N-Methyl-d-aspartate Receptors

et al. 2019

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“…Vallejos et al [10] reported the experimental investigation of the structure and vibrational properties of methoxycarbonylsulfenyl isocyanate. Pingali et al [11] reported a highly orally bio available sulfonyl derivative as a potent hypoglycaemic and hypolipidemic agent. Yang et al [12] reported the new preparation of difluoroiodomethylsulfanylbenzenes and their radical addition to unsaturated compounds initiated by sodium dithionite.…”

Section: Introductionmentioning

confidence: 99%

FT-IR, HOMO–LUMO, NBO, MEP analysis and molecular docking study of 3-Methyl-4-{(E)-[4-(methylsulfanyl)-benzylidene]amino}1H-1,2,4-triazole-5(4H)-thione

Panicker¹,

Varghese

Manjula³

et al. 2015

Spectrochimica Acta Part A: Molecular and Biomolecular Spectros

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“…Yang et al [8] reported a new method of preparation of difluoroiodomethylsulfanylbenzenes and their radical addition to unsaturated compounds initiated by sodium dithionite. Synthesis and structure-activity relationships of 4-alkynyloxy phenyl sulfanyl, sulfinyl, and sulfonyl alkyl hydroxamates as tumor necrosis factor-α converting enzyme and matrix metalloproteinase inhibitors were reported by Venkatesan et al [9] Pingali et al [10] reported the highly orally bioavailable c-5- [6-(4-methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane-r-2-carboxylic acid as a potent hypoglycemic and hypolipidemic agent. The synthesis of a series of 2-benzenesulfonylalkyl-5-substituted-sulfanyl- [1,3,4]oxadiazoles and the examination of their anti-hepatitis B virus activity have also been reported.…”

Section: Introductionmentioning

confidence: 98%

Vibrational spectroscopic studies and computational study of methyl(2‐methyl‐4,6–dinitrophenylsulfanyl)ethanoate

Panicker¹,

Raj²,

Varghese

et al. 2010

J Raman Spectroscopy

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FT-IR and FT-Raman spectra of methyl(2-methyl-4,6-dinitrophenylsulfanyl)ethanoate (MDIE) were recorded and analyzed. Surface-enhanced Raman scattering (SERS) spectra were recorded in silver colloid and silver electrode. The vibrational wavenumbers were computed using HF/6-31G * and B3LYP/6-31G * basis. The data obtained from vibrational wavenumber calculations are used to assign vibrational bands obtained in infrared and Raman spectroscopies as well as in SERS of the studied molecule. The first hyperpolarizability and infrared intensities are reported. The geometrical parameters of the title compound are in agreement with the reported similar derivatives. The presence of new bands at 1045 and 948 cm −1 in the SERS spectrum in silver electrode is related to the change in orientation of the molecule with respect to the metal surface. In silver colloid SERS spectrum, the methyl group attached to the methoxy carbonyl group is close to the metal surface, whereas on silver electrode the methyl group attached to the phenyl ring is close to the metal surface.

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Discovery of a highly orally bioavailable c-5-[6-(4-Methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane-r-2-carboxylic acid as a potent hypoglycemic and hypolipidemic agent

Cited by 12 publications

References 23 publications

Structure–Affinity Relationships of 2,3,4,5-Tetrahydro-1H-3-benzazepine and 6,7,8,9-Tetrahydro-5H-benzo[7]annulen-7-amine Analogues and the Discovery of a Radiofluorinated 2,3,4,5-Tetrahydro-1H-3-benzazepine Congener for Imaging GluN2B Subunit-Containing N-Methyl-d-aspartate Receptors

Structure–Affinity Relationships of 2,3,4,5-Tetrahydro-1H-3-benzazepine and 6,7,8,9-Tetrahydro-5H-benzo[7]annulen-7-amine Analogues and the Discovery of a Radiofluorinated 2,3,4,5-Tetrahydro-1H-3-benzazepine Congener for Imaging GluN2B Subunit-Containing N-Methyl-d-aspartate Receptors

FT-IR, HOMO–LUMO, NBO, MEP analysis and molecular docking study of 3-Methyl-4-{(E)-[4-(methylsulfanyl)-benzylidene]amino}1H-1,2,4-triazole-5(4H)-thione

Vibrational spectroscopic studies and computational study of methyl(2‐methyl‐4,6–dinitrophenylsulfanyl)ethanoate

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