Sulfoximine- and Sulfilimine-Based DAPSON Analogues; Syntheses and Bioactivities

Xiao Yun Chen; Helmut Buschmann; Carsten Bolm

doi:10.1055/s-0032-1317493

Synlett, Table of Contents

Synlett 2012; 23(19): 2808-2810
DOI: 10.1055/s-0032-1317493

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Sulfoximine- and Sulfilimine-Based DAPSON Analogues; Syntheses and Bioactivities

Xiao Yun Chen

^aInstitute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany Fax: +49(241)8092391 Email: carsten.bolm@oc.rwth-aachen.de

,

Helmut Buschmann

^bSperberweg 15, 52076 Aachen, Germany

,

Carsten Bolm*

^aInstitute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany Fax: +49(241)8092391 Email: carsten.bolm@oc.rwth-aachen.de

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Abstract

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Abstract

Sulfoximine- and sulfilimine-based diamino-diphenyl sulfone (DAPSON) analogues have been prepared and their COX-1 and COX-2 inhibition potencies as well as LTB₄ and TNF binding properties were studied. Furthermore, their antiproliferative activities on cancer cell growth were investigated. Neither compounds showed significant bioactivities.

Key words

drug discovery - cancer - oxidation - sulfoximine - sulfilimine

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References

References
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10 General procedure for the synthesis of N-cyano sulfoximine from the corresponding sulfide: Step 1: To a solution of sulfide (1 mmol) and NH₂CN (63.0 mg, 1.5 mmol) in DMF (5 mL), PhI(OAc)₂ (354.3 mg, 1.1 mmol) was added. The reaction was stirred at 0 °C for 30 min and then warmed to r.t. (substrate conversion was monitored by TLC). When the starting material was no longer consumed, the reaction mixture was diluted with H₂O (30 mL) and extracted with CH₂Cl₂ (4 × 15 mL). The combined organic layers were washed with sat. NaHCO₃, H₂O, and brine, and dried over MgSO₄. The purified sulfilimine was obtained by silica gel column chromatography. Step 2: To a stirring solution of N-cyanosulfilimine (1 mmol) in MeOH (10 mL) was added K₂CO₃ (414.6 mg, 3.0 mmol) and MCPBA (258.9 mg, 1.5 mmol) at 0 °C. The mixture was stirred at room temperature until the starting material was consumed (ca. 6 h). The solvent was then removed under reduced pressure, H₂O (20 mL) was added and the resulting mixture was extracted with CH₂Cl₂ (4 × 15 mL). The combined organic layers were dried over MgSO₄, and column chromatography (silica gel) provided the purified N-cyano sulfoximine.

These assays were performed by Ricerca Biosciences, Chicago, USA. Methods:

11a COX-1: human platelets (source); 100 μM arachidonic acid (substrate); EIA quantification of PGE₂ (quantification method).
11b COX-2: human recombinant insect Sf21 cells (source); 0.3 μM arachidonic acid (substrate); EIA quantification of PGE₂ (quantification method).
11c LTB₄: human U937 cells (source); 0.2 nM [³H] LTB₄ (ligand); radioligand binding (quantification method).
11d TNF: human U937 cells (source); 0.028 nM [¹²⁵I] TNF-α (ligand); radioligand binding (quantification method). For details see the Supporting Information.

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14 For the original One Dose Mean Graphs provided by the NCI, see the Supporting Information.
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Supplementary Material

Supporting Information