Brief Articles
Journal of Medicinal Chemistry, 2007, Vol. 50, No. 2 393
(
m, 2H), 1.24 (m, 22H), 0.85 (t, J ) 6.7 Hz, 3H). 13C NMR (75
(5) Xu, Y.; et al. Design and synthesis of a potent and selective
triazolone-based PPARR agonist. J. Med. Chem. 2003, 46, 5121-
5124.
MHz, CDCl ) : 129.9, 129.7, 43.6, 31.8, 29.7-26.6, 27.1, 27.2,
2
SO , 346.57): C, H, N, S.
2
General Procedure for the Preparation of Disubstituted
Sulfamides 6-12. Freshly distilled N-propylsulfamoyl chloride was
added dropwise to a solution of the amine and TEA in dry toluene
at 0 °C under a nitrogen atmosphere. The reaction mixture was
stirred at room temperature, the white solid formed was filtered,
the solvent was evaporated to dryness, and the crude was purified
3
+
+
38 2
2.6, 14.1. MS (ES ) [M + H] 347 (100%). Anal. (C18H N -
(
(
(
6) Forman, B. M.; Chen, J.; Evans, R. M. Hypolipidemic drugs,
polyunsaturated fatty acids, and eicosanoids are ligands for peroxi-
some proliferator-activated receptors alpha and delta. Proc. Natl.
Acad. Sci. U.S.A. 1997, 94, 4312-4317.
7) Rodr ´ı guez De Fonseca, F.; Navarro, M.; G o´ mez, R.; Escuredo, L.;
Nava, F.; Fu, J.; Murillo, E.; Giuffrida, A.; Loverne, J.; Gaetani, S.;
Kathuria, S.; Gali, C.; Piomelli, D. An anorexic lipid mediator
regulated by feeding. Nature 2001, 414, 209-212.
8) Fu, J.; Gaetani, S.; Oveisi, F.; Lo Verme, J.; Serrano, A.; Rodr ´ı guez
De Fonseca, F.; Rosengarth, A.; Luecke, H.; Di Giacomo, B.; Tarzia,
G.; Piomelli, D. Oleylethanolamide regulates feeding and body weight
through activation of the nuclear receptor PPAR-R. Nature 2003,
by column chromatography on silica gel with CH
:1, giving the desired product.
The preparation of N-octadecy-N′-propylsulfamide (7) is given
2
Cl
2
/MeOH+NH
3
9
as representative example.
N-Octadecyl-N′-propylsulfamide (7). From N-octadecylamine
425, 90-93.
(0.270 g, 1.0 mmol), N-propylsulfamoyl chloride (0.157 g, 1.0
(9) Fu, J.; Oveisi, F.; Gaetani, S.; Lin, E.; Piomelli, D. Oleoylethano-
lamide, and endogenous PPARR agonist, lowers body weight and
hyperlipidemia in obese rats. Neuropharmacology 2005, 48, 1147-
1153.
mmol), TEA (0.300 g, 3.0 mmol), and toluene (30 mL); reaction
time, 24 h; yield ) 0.122 g of white solid, 31%; mp ) 110-112
°
1
C; H NMR (400 MHz, CDCl
3
) 3.01 (m, 4H), 1.53 (m, 4H), 1.24
(
br m, 30H), 0.94 (t, J ) 7.6 Hz, 3H), 0.86 (t, J ) 6.8 Hz, 3H).
(10) Cano, C.; P a´ ez J. A.; Goya, P.; Pavon, J.; Macias, M.; Rodr ´ı guez
De Fonseca, F.; Derivados ac ´ı clicos saturados e insaturados de cadena
larga de sulfamidas como activadores espec ´ı ficos de PPARR. Pat.
Esp. P200600184, 2006.
13
C NMR (100 MHz, CDCl
2.9, 22.6, 14.1, 11.2; MS (ES ) [M + H] 391 (100%). Anal.
SO , 390.67): C, H, N, S.
3
) 45.0, 43.3, 31.9, 29.7-29.2, 26.7,
+
+
2
(
C H
21 46
N
2
2
(
11) (a) Paquin, A. M. Neue verbindungen und reaktionen des sulfamids.
Angew. Chem. 1948, 60, 316-320. (b) McDermott, S. D.; Spillane,
W. J. Synthesis and reactions of sulfamides, a review. Org. Prep.
Proced. Int. 1984, 16, 49-77.
Acknowledgment. This study was supported by Consejeria
de Salud de la Junta de Andalucia, Instituto de Salud Carlos III
PI02/001, PI04/0834, and CP04/00039), Grants 02/001, Redes
Tem a´ ticas FIS RCMN (C03/08) and Red de Obesidad (G03/
28), and MEC Grant SAF 2004-07762 and SAF 2003-08003.
(
(
12) Atkins, G. M., Jr.; Burgess, E. M. Synthesis and reactions of
N-sulfonylamines. J. Am. Chem. Soc. 1972, 94, 6135-6141.
13) Kloek, J. A.; Leschinsky, K. L. An improved synthesis of sulfamoyl
chlorides. J. Org. Chem. 1976, 41, 4028-4029.
0
(
C.C. is recipient of I3P fellowship from the C.S.I.C. C.C. and
J.P. contributed equally to the present study.
(14) Odenwaelder, H.; Pueschel, W.; Ranz, E. Light-sensitive color
photographic material. Ger. Offen. 1979, 36.
Supporting Information Available: Experimental details and
CHNS analysis. This material is available free of charge via the
Internet at http://pubs.acs.org.
(
15) Macias-Gonzalez, M.; Samenfeld, P.; Perkyla, M.; Carlberg, C.
Corepressor excess shifts the two-side chain vitamin D analog gemini
from an agonist to an inverse agonist of the vitamin D receptor. Mol.
Endocrinol. 2003, 17, 2028-2038.
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