2076 Journal of Medicinal Chemistry, 2007, Vol. 50, No. 9
Samant et al.
(12) Qasmi, D.; Rene´, L.; Badet, B. An R-aminoglycine derivative suitable
for solid phase peptide synthesis using Fmoc strategy. Tetrahedron
Lett. 1993, 34, 3861-3862.
(13) Kingsbury, W. D.; Boehm, J. C.; Perry, D.; Gilvarg, C. Portage of
various compounds into bacteria by attachment to glycine residues
in peptides. Proc. Natl. Acad. Sci. U.S.A. 1984, 81, 4573-4576.
(14) Kingsbury, W. D.; Boehm, J. C. Synthesis of alpha-thiophenylgly-
cine peptides. Novel peptide substrates useful in the study of
microbial peptide transport. Int. J. Pept. Protein Res. 1986, 27, 659-
665.
(15) Samant, M. P.; Rivier, J. E. Norcystine, a new tool for the study of
the structure-activity relationship of peptides. Org. Lett. 2006, 8,
2361-2364.
(16) Watson, A. A.; Fairlie, D. P.; Craik, D. J. Solution structure of
methionine-oxidized amyloid beta-peptide (1-40). Does oxidation
affect conformational switching? Biochemistry 1998, 37, 12700-
12706.
(17) Jiang, L.; Burgess, K. Oxidative induction of beta-turn conformations
in cyclic peptidomimetics: conformational analyses as indicators of
configuration. J. Am. Chem. Soc. 2002, 124, 9028-9029.
(18) Schenck, H. L.; Dado, G. P.; Gellman, S. H. Redox-triggered
secondary structure changes in the aggregated states of a de-
signed methionine-rich peptide. J. Am. Chem. Soc. 1996, 118, 12487-
12494.
(19) Dado, G. P.; Gellman, S. H. Redox control of secondary structure in
a designed peptide. J. Am. Chem. Soc. 1993, 115, 12609.
(20) Cetel, N. S.; Rivier, J.; Vale, W.; Yen, S. S. C. The dynamics of
gonadotropin inhibition in women induced by an antagonistic
analogue of gonadotropin-releasing hormone. J. Clin. Endocrinol.
Metab. 1983, 57, 62-65.
(21) Rivier, J.; Porter, J.; Rivier, C.; Perrin, M.; Corrigan, A.; Hook, W.
A.; Siraganian, R. P.; Vale, W. W. New effective gonadotropin
releasing hormone antagonists with minimal potency for histamine
release in Vitro. J. Med. Chem. 1986, 29, 1846-1851.
(22) Theobald, P.; Porter, J.; Rivier, C.; Corrigan, A.; Perrin, M.; Vale,
W.; Rivier, J. Novel gonadotropin releasing hormone antagonist:
Peptides incorporating modified Nω-cyanoguanidino moieties. J. Med.
Chem. 1991, 34, 2395-2402.
(23) Rivier, J.; Porter, J.; Hoeger, C.; Theobald, P.; Craig, A. G.; Dykert,
J.; Corrigan, A.; Perrin, M.; Hook, W. A.; Siraganian, R. P.; Vale,
W.; Rivier, C. Gonadotropin releasing hormone antagonists with Nω-
triazolyl-ornithine, -lysine or -para-aminophenylalanine residues at
positions 5 and 6. J. Med. Chem. 1992, 35, 4270-4278.
(24) Rivier, J. E.; Jiang, G.; Porter, J.; Hoeger, C.; Craig, A. G.; Corrigan,
A. Z.; Vale, W. W.; Rivier, C. L. GnRH antagonists: novel members
of the azaline B family. J. Med. Chem. 1995, 38, 2649-2662.
(25) Karten, M. J.; Rivier, J. E. GnRH analog design structure-function
studies toward the development of agonists and antagonists: Ratio-
nale and perspective. Endocr. ReV. 1986, 7, 44-66.
(35) Jiang, G.; Rivier, J. Novel, Water Soluble and Long Acting GnRH
Antagonists. Peptides for the New Millennium, Proceedings of the
Sixteenth American Peptide Symposium, Minneapolis, MN, June 26
to July 1, 1999; Kluwer Academic Publishers: Dordrecht, The
Netherlands, 2000; p 286.
(36) Samant, M. P.; Gulyas, J.; Hong, D. J.; Croston, G.; Rivier, C.; Rivier,
J. Iterative approach to the discovery of novel degarelix analogues:
substitutions at positions 3, 7 and 8. Part II. J. Med. Chem. 2005,
48, 4851-4860.
(37) Rivier, J.; Rivier, C.; Perrin, M.; Porter, J.; Vale, W. LHRH Analogs
as Antiovulatory Agents. LHRH and Its AnalogssContraceptiVe and
Therapeutic Applications. AdVances in Reproduction; MTP Press:
Lancaster, U.K., Boston, The Hague, The Netherlands, 1984; pp 11-
22.
(38) Rizo, J.; Koerber, S. C.; Bienstock, R. J.; Rivier, J.; Gierasch, L.
M.; Hagler, A. T. Conformational analysis of a highly potent,
constrained gonadotropin-releasing hormone antagonist. II. Molecular
dynamics simulations. J. Am. Chem. Soc. 1992, 114, 2860-2871.
(39) Bienstock, R. J.; Rizo, J.; Koerber, S. C.; Rivier, J. E.; Hagler, A.
T.; Gierasch, L. M. Conformational analysis of a highly potent
dicyclic gonadotropin-releasing hormone antagonist by nuclear
magnetic resonance and molecular dynamics. J. Med. Chem. 1993,
36, 3265-3273.
(40) Sherwood, N.; Eiden, L.; Brownstein, M.; Spiess, J.; Rivier, J.; Vale,
W. Characterization of a teleost gonadotropin-releasing hormone.
Proc. Natl. Acad. Sci. U.S.A. 1983, 80, 2794-2798.
(41) Lovejoy, D. A.; Fischer, W. H.; Ngamvongchon, S.; Craig, A. G.;
Nahorniak, C. S.; Peter, R. E.; Rivier, J. E.; Sherwood, N. M. Distinct
sequence of gonadotropin-releasing hormone (GnRH) in dogfish brain
provides insight into GnRH evolution. Proc. Natl. Acad. Sci. U.S.A.
1992, 89, 6373-6377.
(42) Miyamoto, K.; Hasegawa, Y.; Minegishi, T.; Nomura, M.; Takahashi,
Y.; Igarashi, M.; Kanagawa, K.; Matsuo, H. Isolation and charac-
terization of chicken hypothalamic luteinizing hormone-releasing
hormone. Biochem. Biophys. Res. Commun. 1982, 106, 820.
(43) Sherwood, N. M.; Sower, S. A.; Marshak, D. R.; Fraser, B. A.;
Brownstein, M. J. Primary structure of gonadotropin-releasing
hormone from lamprey brain. J. Biol. Chem. 1986, 261, 4812-4819.
(44) Sower, S. A.; Chiang, Y. C.; Lovas, S.; Conlon, J. M. Primary
structure and biological activity of a third gonadotropin- releasing
hormone from lamprey brain. Endocrinology 1993, 132, 1125-1131.
(45) Powell, J. F. F.; Reska-Skinner, S. M.; Prakash, O. M.; Fischer, W.
H.; Park, M.; Rivier, J. E.; Craig, A. G.; Mackie, G. O.; Sherwood,
N. M. Two new forms of gonadotropin-releasing hormone in a
protochordate and the evolutionary implications. Proc. Natl. Acad.
Sci. U.S.A. 1996, 93, 10461-10464.
(46) Adams, B. A.; Tello, J.; Erchegyi, J.; Warby, C.; Hong, D. J.;
Akinsanya, K. O.; Mackie, G. O.; Vale, W.; Rivier, J. E.; Sherwood,
N. M. Six novel GnRH hormones are encoded as triplets on each of
two genes in protochordate Ciona intestinalis. Endocrinology 2003,
144, 1907-1919.
(47) Hocart, S. J.; Nekola, M. V.; Coy, D. H. Improved antagonists of
luteinizing hormone-releasing hormone modified in position 7. J.
Med. Chem. 1985, 28, 967.
(48) Rivier, J.; Varga, J.; Porter, J.; Perrin, M.; Rivier, C.; Vale, W.;
Struthers, S.; Hagler, A. Design of Cyclic GnRH Antagonists. The
GnRH Satellite Symposium, 7th International Congress of Endocri-
nology, Quebec, Canada, June 28-30, 1984; 1984.
(26) Jiang, G.; Stalewski, J.; Galyean, R.; Dykert, J.; Schteingart, C.;
Broqua, P.; Aebi, A.; Aubert, M. L.; Semple, G.; Robson, P.;
Akinsanya, K.; Haigh, R.; Riviere, P.; Trojnar, J.; Junien, J. L.; Rivier,
J. E. GnRH antagonists: A new generation of long acting analogues
incorporating urea functions at positions 5 and 6. J. Med. Chem. 2001,
44, 453-467.
(27) Goulet, M. T. Gonadotropin Releasing Hormone Antagonists. Annual
Reports in Medicinal Chemistry; Academic Press: New York, 1995;
pp 169.
(28) Sundaram, K.; Didolkar, A.; Thau, R.; Chaudkuri, M.; Schmidt, F.
Antagonists of luteinizing hormone releasing hormone bind to rat
mast cells and induce histamine release. Agents Actions 1988, 25,
307-313.
(29) Herbst, K. L.; Coviello, A. D.; Page, S.; Amory, J. K.; Anawalt, B.
D.; Bremner, W. J. A single dose of the potent gonadotropin-releasing
hormone antagonist acyline suppresses gonadotropins and testosterone
for 2 weeks in healthy young men. J. Clin. Endocrinol. Metab. 2004,
89, 5959-5965.
(49) Fujino, M.; Kobayashi, S.; Obayashi, M.; Sinagawa, S.; Fukuda, T.;
Kitada, C.; Nakayama, R.; Yamazaki, I.; White, W. F.; Rippel, R.
H. Structure-activity relationships in the C-terminal part of luteinizing
hormone releasing hormone (LH-RH). Biochem. Biophys. Res.
Commun. 1972, 49, 863-869.
(50) Knollman, P. E.; Janovick, J. A.; Brothers, S. P.; Conn, P. M. Parallel
regulation of membrane trafficking and dominant-negative effects
by misrouted gonadotropin-releasing hormone receptor mutants. J.
Biol. Chem. 2005, 280, 24506-24514.
(30) Herbst, K. L.; Anawalt, B. D.; Amory, J. K.; Bremner, W. J.
Acyline: the first study in humans of a potent, new gonadotropin-
releasing hormone antagonist. J. Clin. Endocrinol. Metab. 2002, 87,
3215-3220.
(51) Anderes, K. L.; Luthin, D. R.; Castillo, R.; Kraynov, E. A.; Castro,
M.; Nared-Hood, K.; Gregory, M. L.; Pathak, V. P.; Christie, L. C.;
Paderes, G.; Vazir, H.; Ye, Q.; Anderson, M. B.; May, J. M.
Biological characterization of a novel, orally active small molecule
gonadotropin-releasing hormone (GnRH) antagonist using castrated
and intact rats. J. Pharmacol. Exp. Ther. 2003, 305, 688-695.
(52) Samant, M. P.; Hong, D. J.; Croston, G.; Rivier, C.; Rivier, J. Novel
analogues of degarelix incorporating hydroxy-, methoxy- and pegy-
lated- urea moieties at residues 3, 5, 6 and the N-terminus. Part III.
J. Med. Chem. 2006, 49, 3536-3543.
(53) Ljungqvist, A.; Feng, D.-M.; Tang, P.-F. L.; Kubota, M.; Okamoto,
T.; Zhang, Y.; Bowers, C. Y.; Hook, W. A.; Folkers, K. Design,
synthesis and bioassays of antagonists of LHRH which have high
antiovulatory activity and release negligible histamine. Biochem.
Biophys. Res. Commun. 1987, 148, 849-856.
(31) Fersht, A. Enzyme Structure and Mechanism, 2nd ed.; W. H. Freeman
and Co.: New York, 1985.
(32) McCarthy, J. R.; Matthews, D. P.; Paolini, J. P. Reaction of sulfoxides
with diethylaminosulfur trifluoride: Fluoromethyl phenyl sulfone, a
reagent for the synthesis of fluoroalkenes. Org. Synth. 1993, 72, 209.
(33) Boekelheide, V.; Linn, W. J. Rearrangements of N-oxides. A novel
synthesis of pyridyl carbinols and aldehydes. J. Am. Chem. Soc. 1954,
76, 1286-1291.
(34) Bell, T. W.; Cho, Y.-M.; Firestone, A.; Healy, K.; Liu, J.; Ludwig,
R.; Rothenberger, S. D. 9-n-butyl-1,2,3,4,5,6,7,8-octahydroacridin-
4-ol. Org. Synth. 1990, 69, 226.