5596 Journal of Medicinal Chemistry, 2006, Vol. 49, No. 18
Watanabe et al.
(2) (a) Hill, S. J.; Ganellin, C. R.; Timmerman, H.; Schwartz, J.-C.;
Shankley, N. P.; Young, J. M.; Schunack, W.; Levi, R.; Haas, J. L.
International union of pharmacologoy. XIII. Classification of hista-
mine receptors. Pharmacol. ReV. 1997, 49, 253-278. (b) van der
Goot, H.; Timmerman, H. Selective ligands as tools to study
histamine receptors. Eur. J. Med. Chem. 2000, 35, 5-20. (c) Ahang,
M.-Q.; Leurs, R. Histamine H1-receptor antagonists. In Burger’s
Medicinal Chemistry and Drug DiscoVery, 5th ed.; Wolff, M. E.,
Ed.; John Wiley & Sons: New York, 1997; Vol. 5; pp 495-559.
(d) Brown, R. E.; Stevens, D. R.; Haas, H. L. The physiology of
brain histamine. Prog. Neurobiol. 2001, 63, 647-672.
(3) (a) Arrang, J.-M.; Garbarg, M.; Schwartz, J.-C. Auto-inhibition of
brain histamine release mediated by a novel class (H3) of histamine
receptor. Nature 1983, 302, 832-837. (b) Leurs, R., Timmerman,
H., Eds. The Histamine H3 Receptor. A Target for New Drugs;
Elsevier: Amsterdam, The Netherlands, 1998. (c) Lovenberg, T. W.;
Roland, B. L.; Wilson, S. W.; Jiang, X.; Pyati, J.; Huvar, A.; Jackson,
M. R.; Erlander, M. G. Cloning and functional expression of the
human histamine H3 receptor. Mol. Pharmacol. 1999, 55, 1101-
1107. (d) Leurs, R.; Hoffmann, M.; Wieland, K.; Timmerman, H.
H3 receptor gene is cloned at last. Trends Pharmacol. Sci. 2000, 21,
11-12.
(4) (a) Oda, T.; Morikawa, N.; Saito, Y.; Masuho, Y.; Matsumoto, S.
Molecular cloning and characterization of novel type of histamine
receptor preferentially expressed in leukocytes. J. Biol. Chem. 2000,
275, 36781-36786. (b) Nakamura, T.; Itadani, H.; Hidaka, Y.; Ohta,
M.; Tanaka, K. Molecular cloning and characterization of a new
human histamine receptor, HH4R. Biochem. Biophys. Res. Commun.
2000, 279, 615-620. (c) Hough, L. B. Genomics meets histamine
receptors: New subtypes, new receptors. Mol. Pharmacol. 2001, 59,
415-419 and references therin.
(5) (a) Fung-Leung, W. P.; Thurmond, R. L.; Ling, P.; Karlsson, L.
Histamine H4 receptor antagonists: the new antihistamines? Curr.
Opin. InVest. Drugs 2004, 11, 1174-1183. (b) Ling, P.; Ngo, K.;
Nguyen, S.; Thurmond, R. L.; Edwards, J. P.; Karlsson, L.; Fung-
Leung, W. P. Histamine H4 receptor mediates eosinophil chemotaxis
with cell shape change and adhesion molecule upregulation. Br. J.
Pharmacol. 2004, 142, 161-171. (c) Lim, H. D.; van Rijn, R. M.;
Ling, P.; Bakker, R. A. Thurmond, R. L.; Leurs, R. Evaluation of
histamine H1-, H2-, and H3-receptor ligands at the human histamine
H4 receptor: identification of 4-methylhistamine as the first potent
and selective H4 receptor agonist. J. Pharmacol. Exp. Ther. 2005,
314, 1310-1321.
carboxy-3-substituted-cyclopropyl)glycines as useful probes for ex-
citatory amino acid receptors. J. Med. Chem. 1996, 39, 407-423.
(b) Stammer, S. H. Cyclopropane amino acids; 2,3- and 3,4-
methanoamino acids. Tetrahedron 1990, 46, 2231-2254. (c) Martin,
S. F.; Dwyer, M. P.; Hartmann, B.; Knight, K. S. Cyclopropane-
derived peptidomimetics. Design, synthesis, and evaluation of novel
enkephalin analogues. J. Org. Chem. 2000, 65, 1305-1318. (d)
Sekiyama, T.; Hatsuya, S.; Tanaka, Y.; Uchiyama, M.; Ono, N.;
Iwayama, S.; Oikawa, M.; Suzuki, K.; Okunishi, M.; Tsuji, T.
Synthesis and antiviral activity of novel acyclic nucleosides: Dis-
covery of a cyclopropyl nucleoside with potent inhibitory activity
against herpes viruses. J. Med. Chem. 1998, 41, 1284-1298.
(11) (a) Shuto, S.; Ono, S.; Hase, Y.; Kamiyama, N.; Takada, H.;
Yamashita, K.; Matsuda, A. Conformational restriction by repulsion
between adjacent substituents of a cyclopropane ring: Design and
enantioselective synthesis of 1-phenyl-2-(1-aminoalkyl)-N,N-dieth-
ylcyclopropanecarboxamides as potent NMDA receptor antagonists.
J. Org. Chem. 1996, 61, 915-923. (b) Shuto, S.; Ono, S.; Hase, Y.;
Ueno, Y.; Noguchi, T.; Yoshii, K.; Matsuda, A. Synthesis and
biological activity of conformationally restricted analogs of mil-
nacipran: (1S,1R)-1-Phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcy-
clopropanecarboxamide, an efficient noncompetitive N-methyl-D-
aspartic acid receptor antagonist. J. Med. Chem. 1996, 39, 4844-
4852. (c) Shuto, S.; Ono, S.; Imoto, H.; Yoshii, K.; Matsuda, A.
Synthesis and biological activity of conformationally restricted
analogs of milnacipran: (1S,2R)-1-Phenyl-2-[(R)-1-amino-2-propy-
nyl]-N,N-diethylcyclopropanecarboxamide is a novel class of NMDA
receptor channel blocker. J. Med. Chem. 1998, 41, 3507-3514. (d)
Ono, S.; Ogawa, K.; Yamashita, K.; Yamamoto, T.; Kazuta, Y.;
Matsuda, A.; Shuto, S. Conformational analysis of the NMDA
receptor antagonist (1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N-
diethylcyclopropanecarboxamide (PPDC) designed by a novel con-
formational restriction method based on the structural feature of
cyclopropane ring. Chem. Pharm. Bull. 2002, 50, 966-968 and
references therein.
(12) De Esch, I. J. P.; Vollinga, R. C.; Goubitz, K.; Schenk, H.; Appelberg,
U.; Hacksell, U.; Lemstra, S.; Zuiderveld, O. P.; Hoffmann, M.;
Leurs, R.; Merge, W. M. P. B.; Timmerman, H. Characterization of
the binding site of the histamine H3 receptor. 1. Various approaches
to the synthesis of 3-(1H-imidazole-4-yl)cyclopropylamine and
histaminergic activity of (1R,2R)- and (1S,2S)-2-(1H-imidazol-4-yl)-
cyclopropylamine. J. Med. Chem. 1999, 42, 1115-1122.
(13) (a) Ali, S. M.; Tedford, C. E.; Gregory, R.; Handley, M. K.; Yates,
S. L.; Hirth, W. W.; Phillips, J. G. Design, synthesis, and structure-
activity relationships of acetylene-based histamine H3 receptor
antagonists. J. Med. Chem. 1999, 42, 903-909. (b) Liu, H.; Kerdesky,
F. A.; Black, L. A.; Fitzgerald, M.; Henry, R.; Esbenshade, T. A.;
Hancock, A. A.; Bennani, Y. L. An efficient multigram synthesis of
the potent histamine H3 antagonist GT-2331 and the reassessment
of the absolute configuration. J. Org. Chem. 2004, 69, 192-194.
(14) Davis, A. M.; Teague, S. J. Hydrogen bonding, hydrophobic
interactions and failure of the rigid receptor hypothesis. Angew.
Chem., Int. Ed. 1999, 38, 736-749.
(15) (a) Ahang, M.-Q.; Leurs, R.; Timmerman, H. Histamine H1-receptor
antagonists. In Burger’s Medicinal Chemistry and Drug DiscoVery,
5th ed.; Wolff, M. E., Ed.; John Wiley & Sons: New York, 1997;
Vol. 5; pp 495-559. (b) Timmerman, H.; Smith, R. D. Major classes
of currently established antihypertensive drugs. In Burger’s Medicinal
Chemistry and Drug DiscoVery, 5th ed.; Wolff, M. E., Eds.; John
Wiley & Sons: New York, 1997; Vol. 2; pp 278-299.
(16) (a) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-Y.; Yip, Y.-C. Use of
cyclopropanes and their derivatives in organic synthesis. Chem. ReV.
1989, 89, 165-198. (b) Singh, V. K.; DattaGupta, A.; Sekar, G.
Catalytic enantioselective cyclopropanation of olefins using carbenoid
chemistry. Synthesis 1997, 137-149. (c) Doyle, M. P.; Protopopova,
M. N. New aspects of catalytic asymmetric cyclopropanation.
Tetrahedron 1998, 54, 7919-7946. (d) Cossy, J.; Blanchard, N.;
Meyer, C. Stereoselective synthesis of cyclopropanes bearing adjacent
stereocenters. Synthesis 1999, 1063-1075.
(17) (a) Kazuta, Y.; Abe, H.; Yamamoto, T.; Matsuda, A.; Shuto, S. A
systematic study of the hydride reduction of cyclopropyl ketones with
structurally simplified substrates. Highly stereoselective reductions
of trans-substituted cyclopropyl ketones via the bisected s-cis-
conformation. J. Org. Chem. 2003, 68, 3511-3521. (b) Kazuta, Y.;
Abe, H.; Matsuda, A.; Shuto, S. Highly stereoselective Grignard
addition to cis-substituted C-cyclopropylaldonitrones. The bisected
s-trans transition state can be stabilized effectively by the Lewis acid-
coordination. J. Org. Chem. 2004, 69, 9143-9150 and references
therein.
(6) (a) Jablonowski, J. A.; Grice, C. A.; Chai, W.; Dvorak, C. A.;
Venable, J. D.; Kwok, A. K.; Ly, K. S.; Wei, J.; Baker, S. M.; Desai,
P. J.; Jiang, W.; Wilson, S. J.; Thurmond, R. L.; Karlsson, L.;
Edwards, J. P.; Lovenberg, T. W.; Carruthers, N. I. The first potent
and selective non-imidazole human histamine H4 receptor antagonists.
J. Med. Chem. 2003, 46, 3957-3960. (b) Thurmond, R. L.; Desai,
P. J.; Dunford, P. J.; Fung-Leung, W. P.; Hofstra, C. L.; Jiang, W.;
Nguyen, S.; Riley, J. P.; Sun, S.; Williams, K. N.; Edwards, J. P.;
Karlsson, L. A potent and selective histamine H4 receptor antagonist
with anti-inflammatory properties. J. Pharmacol. Exp. Ther. 2004,
309, 404-413. (c) Terzioglu, N.; van Rijn, R. M.; Bakker, R. A.;
De Esch I. J. P.; Leurs, R. Synthesis and structure-activity
relationships of indole and benzimidazole piperazines as histamine
H4 receptor antagonists. Bioorg. Med. Chem. Lett. 2004, 14, 5251-
5256. (d) Venable, J. D.; Cai, H.; Chai, W.; Dvorak, C. A.; Grice,
C. A.; Jablonowski, J. A.; Shah, C. R.; Kwok, A. K.; Ly, K. S.; Pio,
B.; Wei, J.; Desai, P. J.; Jiang, W.; Nguyen, S.; Ling, P.; Wilson, S.
J.; Dunford, P. J.; Thurmond, R. L.; Lovenberg, T. W.; Karlsson,
L.; Carruthers, N. I.; Edwards, J. P. Preparation and biological
evaluation of indole, benzimidazole, and thienopyrrole piperazine
carboxamides: potent human histamine H4 antagonists. J. Med.
Chem. 2005, 48, 8289-8298.
(7) (a) Kazuta, Y.; Matsuda, A.; Shuto, S. Development of versatile cis-
and trans-dicarbon-substituted chiral cyclopropane units: synthesis
of (1S,2R)- and (1R,2R)-2-aminomethyl-1-(1H-imidazol-4-yl)cyclo-
propanes and their enantiomers as conformationally restricted
analogues of histamine. J. Org. Chem. 2002, 67, 1669-1677. (b)
Kazuta, Y.; Hirano, K.; Natsume, K.; Yamada, S.; Kimura, R.;
Matsumoto, S.; Furuichi, K.; Matsuda, A.; Shuto, S. (1S,2S)-2-(2-
Aminoethyl)-1-(1H-imidazol-4-yl)cyclopropane, a highly selective
agonist for the histamine H3 receptor, having a cis-cyclopropane
structure. J. Med. Chem. 2003, 46, 1980-1988.
(8) Kier, L. B. Molecular orbital calculations of the preferred conforma-
tions of histamine and a theory on its dual activity. J. Med. Chem.
1968, 11, 441-445.
(9) Silverman, R. B. The Organic Chemistry of Drug Design and Drug
Action; Academic Press: San Diego, CA, 2004.
(10) For examples, see the following. (a) Shimamoto, K.; Ofune, Y.
Syntheses and conformational analyses of glutamate analogs: 2-(2-
JM0603318