Journal of Medicinal Chemistry
Brief Article
C8-RP stationary phase (150 mm × 4.6 mm, dp = 5 μm) with UV-
DAD, based on the area under the curve as calculated by Agilent
ChemStation revision A.09.03 for individual measurement at 230 and
254 nm and by recording HR-MS data on a Bruker Apex II FT-ICR-
MS or a Finnigan MAT95 (EI) instrument. All compounds have a
purity of >95%.
the Prostaglandin E2 Production Pathway in Human Pancreatic
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General Procedure for Activation of Carboxylic Acids and
Coupling with Sulfonamides. Carboxylic acid (1 mmol) and CDI
(1.5 mmol) in dry THF (15 mL) were stirred for 3 h. To sulfonamide
(2.5 mmol) in dry THF was added NaH (mineral oil suspension, 1.2
mmol). The mixture was stirred for 3 h and was slowly added to the
activated carboxylic acid. After being stirred overnight, the mixture was
poured into cold water, adjusted to pH 1, and extracted with EtOAc.
Purification was by recrystallization or flash chromatography.
2-(3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-N-tosylaceta-
mide (9) was obtained from lonazolac (1.59 mmol, 0.5 g). The crude
product was purified using methanol to yield 0.45 g (60%) of white
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1
solid product. H NMR (200 MHz, DMSO-d6): δ [ppm] = 2.3 (s,
3H), 3.69 (s, 2H), 7.35 (m, 5H), 7.49 (4H), 7.7 (4H), 8.3 (s, 1H),
12.2 (s, 1H, NH). IR (ATR) 3253, 2924, 2160, 1707, 1598, 1504,
1437, 1177, 1121, 1086, 1011, 860, 834, 817, 751, 686, 673 cm−1.
Purity (HPLC) 98%. Mp 186.6 °C. HR-MS (FT-ICR-MS) for
C24H20ClN3O3S [M + H]+: 466.098.
ASSOCIATED CONTENT
* Supporting Information
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S
Synthesis details and analytical data (NMR, IR, HPLC, MS) of
all compounds; biological assay details. This material is
AUTHOR INFORMATION
Corresponding Author
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*Phone: +49-7071-2978788. Fax: +49-7071-295037. E-mail:
Notes
The authors declare no competing financial interest.
(14) De Luca, L.; Giacomelli, G.; Masala, S.; Porcheddu, A. Mild
Procedure for the Preparation of 3-Aryl-4-formylpyrazoles. Synlett
2004, 13, 2299−2302.
ACKNOWLEDGMENTS
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Thanks are extended to C. Krause, D. Wistuba, and P. Haiss for
HRMS results. This research was financially supported by the
(15) Rainer, G.; Kruger, U.; Klemm, K. Synthesis and Physico-
Chemical Properties of Lonazolac-Ca, a New Antiphlogistic/
Antirheumatic Agent. Arzneim. Forsch. 1981, 31, 649−654.
(16) Koeberle, A.; Siemoneit, U.; Buhring, U.; Northoff, H.; Laufer,
S.; Albrecht, W.; Werz, O. Licofelone Suppresses Prostaglandin E2
Formation by Interference with the Inducible Microsomal Prosta-
glandin E2 Synthase-1. J. Pharmacol. Exp. Ther. 2008, 326, 975−982.
(17) Siemoneit, U.; Hofmann, B.; Kather, N.; Lamkemeyer, T.;
Madlung, J.; Franke, L.; Schneider, G.; Jauch, J.; Poeckel, D.; Werz, O.
Identification and Functional Analysis of Cyclooxygenase-1 as a
Molecular Target of Boswellic Acids. Biochem. Pharmacol. 2008, 75,
503−513.
Landesgraduiertenforderung program of the Ministry of
̈
Science, Research and Arts of the state of Baden-Wurttemberg,
̈
Germany.
ABBREVIATIONS USED
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AA, arachidonic acid; CDI, 1,1-carbonyldiimidazole; 12-HHT,
12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid; TBTU, 2-
(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluor-
oborate; XPhos, 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-
biphenyl
(18) Wang, J.; Limburg, D.; Carter, J.; Mbalaviele, G.; Gierse, J.;
Vazquez, M. Selective Inducible Microsomal Prostaglandin E2
Synthase-1 (mPGES-1) Inhibitors Derived from an Oxicam Template.
Bioorg. Med. Chem. Lett. 2010, 20, 1604−1609.
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