X. Y. Chen et al. / Bioorg. Med. Chem. Lett. 22 (2012) 4307–4309
4309
13. For example, see the inhibition of the glutathione biosynthesis by buthionine
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Pharm. Bull. 2010, 33, 556; (b) Ong, P.-S.; Chan, S.-Y.; Ho, P. C. Int. J. Oncol. 2011,
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14. For selected examples in medicinal chemistry, see: (a) Kahraman, M.; Sinishtaj,
S.; Dolan, P. M.; Kensler, T. W.; Peleg, S.; Saha, U.; Chuang, S. S.; Bernstein, G.;
Korczak, B.; Posner, G. H. J. Med. Chem. 2004, 47, 6854; (b) Raza, A.; Sham, Y. Y.;
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inhibition and receptor binding. In contrast to the sulfone-based
analog, all sulfoximines showed low COX inhibitory potency. Also
their binding to the estrogen receptors differed. While the sulfone
was selective and moderately active for ER b, the sulfoximines
were essentially ER
ab unselective with remarkable inhibitions of
up to 91% and 80% for ER
a
and ER b, respectively. Subsequent
studies shall focus on testing these and other sulfoximine-based
molecules in additional enzyme inhibitory assays and confirm
the opportunities on modifying biological profiles by replacing sin-
gle atoms by other molecular units in core fragments of drug-like
molecules.22
Acknowledgments
Support by the Fonds der Chemischen Industrie is greatly
appreciated. X.Y.C. thanks the China Scholarship Council for a doc-
toral stipend, and M.D.R. acknowledges support by the University
of Siena for a pre-doctoral fellowship allowing her to perform re-
search at RWTH Aachen University.
16. This observation was in line with data reported by Pfizer on inhibition studies
of proline-rich tyrosine kinase 2. For details see Ref. 14c.
17. (a) Mancheño, O. G.; Bolm, C. Org. Lett. 2007, 9, 2951; (b) Mancheño, O. G.;
Bistri, O.; Bolm, C. Org. Lett. 2007, 9, 3809; (c) Pandey, A.; Bolm, C. Synthesis
2010, 2922.
Supplementary data
18. Selected data for product characterization: Compound 8a 1H NMR (400 MHz,
CDCl3): d 7.72–7.65 (m, 2H), 7.37–7.13 (m, 7H), 7.04–6.89 (m, 3H), 6.82–6.74
(m, 2H), 3.23 (s, 3H), 2.42 (t, 2H, J = 7.8 Hz), 1.44–1.08 (m, 4H), 0.73 (t, 3H,
J = 7.1 Hz); 13C NMR (100 MHz, CDCl3) d 151.3, 142.44, 142.39, 141.9, 138.8,
133.2, 131.5, 130.7, 129.3, 128.4, 128.0, 127.5, 127.4, 126.9, 111.9, 45.0, 35.42,
Supplementary data associated with this article can be found, in
31.2, 22.8, 13.9; IR (KBr):
t
= 2195, 1249, 1090, 967 cmꢀ1; MS (EI), m/z (relative
intensity) 414 [M+, 100], 373 [31], 315 [58], 267 [14], 167 [15], 91 [17]; 8b 1H
NMR (300 MHz, CDCl3): d 7.76 (d, 2H, J = 8.6 Hz), 7.44 (d, 2H, J = 8.6 Hz), 7.38–
7.22 (m, 7 H), 7.10–7.04 (m, 2H), 6.90–6.84 (m, H), 3.29 (s, 3 H), 2.18 (s, 3 H);
13C NMR (75 MHz, CDCl3): d 152.2, 142.7, 142.3, 141.8, 133.1, 133.0, 131.1,
130.7, 129.7, 128.7, 128.3, 127.9, 127.5, 127.3, 125.9, 44.8, 22.8; IR (KBr):
References and notes
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t
= 2195, 1097, 965 cmꢀ1; 9a 1H NMR (400 MHz, CDCl3): d 7.75–7.65 (m, 2H),
7.34–7.13 (m, 7H), 7.01–6.88 (m, 3H), 6.84–6.75 (m, 2H), 3.01 (s, 3H), 2.40 (t,
2H, J = 7.8 Hz), 1.45–1.09 (m, 4H), 0.72 (t, 3H, J = 7.1 Hz); 13C NMR (100 MHz,
CDCl3): d 148.4, 142.8, 142.3, 141.3, 140.9, 139.5, 130.74, 130.6, 129.4, 128.4,
127. 8, 127.4, 127.1, 126.5, 46.4, 35.6, 31.2 22.9, 14.0; IR (KBr):
t = 3180, 1261,
1214, 1090, 1006 cmꢀ1; Anal. Calcd for C25H27NOS: C 77.08, H 6.99, N 3.60,
found: C 76.89, H 7.158, N 3.52; HRMS (ESI), m/z: [M+H] Calcd for C25H27NOS
390.1886, found 390.1891; 9b 1H NMR (300 MHz, CDCl3): d 7.76 (d, 2H,
J = 8.4 Hz), 7.40–7.23 (m, 9H), 7.06–7.02 (m, 2H), 6.93–6.80 (m, 1H), 3.06 (s,
3H), 2.31 (bs, 1H), 2.16 (s, 3H); 13C NMR (75 MHz, CDCl3): d 149.6, 142.7, 142.2,
141.5, 140.7, 133.8, 130.7, 130.2, 129.8, 128.2, 127.7, 127.3, 127.0, 126.5, 46.2,
23.0; IR (KBr):
t
= 3274, 1220, 1069, 969 cmꢀ1; Anal. Calcd for C22H21NOS: C
76.04, H 6.09, N 4.03, found: C 75.17, H 5.67, N 3.86; HRMS (ESI), m/z: [M+H]
Calcd for C22H21NOS 348.1415, found 348.1417.
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