ACS Medicinal Chemistry Letters
Letter
(5) Sugimoto, Y.; Narumiya, S.; Ichikawa, A. Distribution and
function of prostanoid receptors: Studies from knockout mice. Prog.
Lipid Res. 2000, 39, 289−314.
(20) Juteau, H.; Gareau, Y.; Labelle, M.; Sturino, C. F.; Sawyer, N.;
̀
Tremblay, N.; Lamontagne, S.; Carriere, M.-C.; Denis, D.; Metters, K.
M. Structure-Activity Relationship of CinnamicAcylsulfonamide
Analogues on the Human EP3 Prostanoid Receptor. Bioorg. Med.
Chem. 2001, 9, 1977−1984.
(6) Narumiya, S.; Sugimoto, Y.; Ushikubi, F. Prostanoid Receptors:
Structures, Properties, and Functions. Physiol. Rev. 1999, 79, 1193−
1226.
̀
(21) Abramowitz, M.; Adam, M.; Boie, Y.; Carriere, M.-C.; Denis, D.;
Godbout, C.; Lamotagne, S.; Rochette, C.; Sawyer, N.; Tremblay, N.
M.; Belley, M.; Gallant, M.; Dufresne, C.; Gareau, Y.; Ruel, R.; Juteau,
H.; Labelle, M.; Ouimet, N.; Metters, K. M. The utilization of
recombinant prostanoid receptors to determine the affinities and
selectivities of prostaglandins and related analogs. Biochim. Biophys.
Acta 2000, 1483, 285−293.
(7) Singh, J.; Zeller, W.; Zhou, N.; Hategan, G.; Mishra, R. K.;
Polozov, A.; Yu, P.; Onua, E.; Zhang, J.; Ramírez, J. L.; Sigthorsson, G.;
Thorsteinnsdottir, M.; Kiselyov, A. S.; Zembower, D. E.; Andresson,
́
T.; Gurney, M. E. Structure-Activity Relationship Studies Leading to
the Identification of (2E)-3-[I-[(2,4-Dichlorophenyl)methyl]-5-fluoro-
3-methyl-IH-indol-7-yl]-N-[(4,5-dichloro-2-thienyl)sulfonyl]-2-prope-
namide (DG-041), a Potent and Selective Prostanoid EP3 Receptor
Antagonist, as a Novel Antiplatelet Agent That Does Not Prolong
Bleeding. J. Med. Chem. 2010, 53, 18−36.
(8) Singh, J.; Zeller, W.; Zhou, N.; Hategan, G.; Mishra, R.; Polozov,
A.; Yu, P.; Onua, E.; Zhang, J.; Zembower, D.; Kiselyov, A.; Ramírez, J.
́
L.; Sigthorsson, G.; Bjornsson, J. M.; Thorsteinsdottir, M.; Andresson,
T.; Bjarnadottir, M.; Magnusson, O.; Fabre, J.-E.; Stafansson, K.;
Gurney, M. E. Antagonists of the EP3 Receptor for Prostaglandin E2
Are Novel Antiplatelet Agents That Do Not Prolong Bleeding. Am.
Chem. Soc. Chem. Biol. 2009, 4, 115−126.
(9) Belley, M.; Gallant, M.; Roy, B.; Houde, K.; Lachance, N.;
Labelle, M.; Trimble, L. A.; Chauret, N.; Li, C.; Sawyer, N.; Tremblay,
(22) Loeffler, I.; Grun, M.; Bohmer, F. D.; Rubio, I. Role of cAMPin
̈
̈
the promotion of colorectal cancer cell growth by Prostaglandin E2.
BMC Cancer 2008, 8, 380−398.
(23) Suzuki, T.; Fujikura, K.; Higashiyama, T.; Takata, K. DNA
Staining for Fluorescence and Laser Confocal Microscopy. J.
Histochem. Cytochem. 1997, 45, 49−53.
(24) Kapuscinski, J. DAPI a DNA-specific fluorescent probe. Biotech.
Histochem. 1995, 70, 220−233.
(25) Breyer, M. D.; Jacobson, H. R.; Davis, I. S.; Breyer, R. M. In situ
hybridization and localization of nRNA for the rabbit prostaglandin
EP3 receptor. Kidney Int. 1993, 43, 1372−1378.
(26) Breyer, M. D.; Davis, L.; Jacobson, H. R.; Breyer, R. M.
Differential localization of prostaglandin E receptor subtypes in human
kidney. Am. J. Physiol. 1996, 270, F912−F918.
̀
N.; Lamontagne, S.; Carriere, M.-C-; Denis, D.; Greig, G. M.; Slipetz,
D.; Metters, K. M.; Gordon, R.; Chan, C. C.; Zamboni, R. J. Structure-
activity relationship studies on ortho-substituted cinnamic acids, a new
class of selective EP3 antagonists. Bioorg. Med. Chem. Lett. 2005, 15,
527−530.
(27) Sugimoto, Y.; Namba, T.; Shigemoto, R.; Negishi, M.; Ichikawa,
A.; Narumiya, S. Distinct cellular localization of mRNAs for three
subtypes of prostaglandin E receptor in kidney. Am. J. Physiol. 1994,
266, F823−F828.
(10) Belley, M.; Chan, C. C.; Gareau, Y.; Gallant, M.; Juteau, H.;
Houde, K.; Lachance, N.; Labell, M.; Sawyer, N.; Tremblay, N.;
Lamontagne, S.; Carriere, M.-C.; Denis, D.; Greig, G. M.; Slipetz, D.;
̀
(28) Morath, R.; Klein, T.; Seyberth, H. W.; Nusing, R M.
̈
Immunolocalization of the Four Prostaglandin E2 Receptor Proteins
EP1, EP2, EP3, and EP4 in Human Kidney. J. Am. Soc. Nephrol. 1999,
10, 1851−1860.
Gordon, R.; Chauret, N.; Li, C.; Zamboni, R. J.; Metters, K. M.
Comparison between two classes of selective EP3 antagonists and their
biological activities. Bioorg. Med. Chem. Lett. 2006, 16, 5639−5642.
(11) Belley, M.; Lachance, N.; Labelle, M.; Gallant, M.; Chauret, N;
Li, C.; Trimble, L. A. Prostaglandin Receptor Ligands. WO Patent
0020371, 2000; Chem. Abstr. 2000, 132, 278987.
(12) Amon, M.; Ligneau, X; Schwartz, J.-C.; Stark, H. Fluorescence
non-imidazole histamine H3 receptor ligands with nanomolar affinities.
Bioorg. Med. Chem. Lett. 2006, 16, 1938−1940.
(29) Sugimoto, Y.; Shigemoto, R.; Namba, T.; Negishi, M.; Mizuno,
N.; Narumiya, S.; Ichikawa, A. Distribution of the messenger RNA for
the prostaglandin E receptor subtype EP3 in the mouse nervous
system. Neuroscience 1994, 62, 919−928.
(30) Cimino, P. J.; Keene, C. D.; Breyer, R. M.; Montine, K. S.;
Montine, T. J. Therapeutic Targets in Prostaglandin E2 Signaling for
Neurologic Disease. Curr. Med. Chem. 2008, 15, 1863−1869.
(13) Amon, M.; Ligneau, X.; Camelin, J.-C.; Berrebi-Bertrand, I.;
Schwartz, J.-C.; Stark, H. Highly potent fluorescence-tagged non-
imidazole histamine H3 receptor ligands. Chem. Med. Chem. 2007, 2,
708−716.
(14) Keller, M.; Erdmann, D.; Pop, N.; Pluym, N.; Teng, S.;
Bernhardt, G.; Buschauer, A. Red-fluorescent argininamide-type NPY
Y1 receptor antagonists as pharmacological tools. Bioorg. Med. Chem.
2011, 19, 2859−2878.
(15) Schneider, E.; Keller, M.; Brennauer, A.; Hoefelschweiger, B. K.;
Gross, D.; Wolfbeis, O. S.; Bernhardt, G.; Buschauer, A. Synthesis and
Characterization of the First Fluorescent Nonpeptide NPY Y1
Receptor Antagonist. Chem. Biol. Chem. 2007, 8, 1981−1988.
(16) Bakthavachalam, V.; Baindur, N.; Madreas, B. K.; Neumeyer, J.
L. Fluorescent Probes for Dopamine Receptors: Synthesis and
Characterization of Fluorescein and 7-Nitrobenz-2-oxa-1,3-dazol-4-yl
Conjugates of D-1 and D-2 Receptor Ligands. J. Med. Chem. 1991, 34,
3235−3241.
(17) Hodl, C.; Strauss, W. S. L.; Sailer, R.; Seger, C.; Steiner, R.;
̈
Haslinger, E.; Schramm, H. W. A Novel, High-Affinity, Fluorescent
Progesterone Receptor Antagonist. Synthesis and in Vitro Studies.
Bioconjugate Chem. 2004, 15, 359−365.
(18) Mitsunobu, O. The Use of Diethyl Azodicarboxylate and
Triphenylphosphine in Synthesis and Transformation of Natural
Products. Synthesis 1981, 1−28.
(19) Renaudet, O.; Dumy, P. Synthesis of multitopicneoglycopep-
tides displaying recognition and detection motifs. Bioorg. Med. Chem.
Lett. 2005, 15, 36193−622.
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