Identification and initial structure-activity relationships of a novel non-peptide quinolone GnRH receptor antagonist

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 17, 1999, Pages 2615-2620

  DeVita, Robert J ^a   Hollings, Darius D ^a   Goulet, Mark T ^a   Wyvratt, Matthew J ^a   Fisher, Michael H ^a   Lo, Jane L ^a   Yang, Yi Tien ^a   Cheng, Kang ^a   Smith, Roy G ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALIPHATIC AMINE; BENZENE DERIVATIVE; GONADORELIN ANTAGONIST; HORMONE RECEPTOR BLOCKING AGENT; LEAD; QUINOLONE DERIVATIVE;

ANIMAL CELL; ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; HYPOPHYSIS CELL; NONHUMAN; RAT; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ANIMALS; PROTEIN BINDING; QUINOLONES; RATS; RECEPTORS, LHRH; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033530102     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00446-1     Document Type: Article

References (17)

1. Matsuo, H.; Baba, Y.; Nair, R.M.G.; Arimura, A.; Schally, A.V. Biochem. Biophys. Res. Comm. 1971, 43, 1334.
2. Conn. P.M.; Janovick, J.A.; Stanislaus, D.; Kuphal, D.; Jennes, L. In Vitamins and Hormones; Litwack, G., Ed.; Academic Press: New York, 1995; Vol. 50, pp 151-214.
3. Barbieri, R.L. Trends Endocrinol. Metab. 1992, 3, 30.
4. Conn, P.M.; Crowley, Jr., W.F.; N. Engl. J. Med. 1991, 324, 93.
5. Goulet, M.T. In Annual Reports in Medicinal Chemistry; Bristol, J.A., Ed.; Academic Press: New York, 1995; Vol. 30, pp 169-178.
6. Kutsher, B.; Bernd, M.; Beckers, T.; Polymeropolis, E.E.; Engel, J. Angew. Chem. Int. Ed. Engl. 1997, 36, 2148.
7. Cho, N.; Harada, M.; Imaeda, T.; Imada, T.; Matsumoto, H.; Hayase, Y.; Sasaki, S.; Furuya, S.; Suzuki, N.; Okubo, S.; Ogi, K.; Endo, S.; Onda, H.; Fujino, M. J. Med. Chem. 1998, 41, 4190.
8. 16
9. Carling, R.W.; Leeson, P.D.; Moore, K.W.; Moyes, C.R.; Duncton, M.; Hudson, M.L.; Baker, R.; Foster, A.C.; Grimwood, S.; Kemp, J.A.; Marshall, G.R.; Tricklebank, M.D.; Saywell, K.L J. Med. Chem. 1997, 40, 754.
10. Methyl anthranilate esters were were prepared with sulfuric acid and methanol or trimethylsilyldiazomethane. 4-Trifluoromethyl anthranilic acid was prepared from 2-nitro-4-trifluoromethyl benzoic acid. 4-Chloro-5-nitro-anthranilic acid is described in the literature: Keyser, G.E.; Leonard, N.J. J. Org. Chem. 1979, 44, 2989.
11. Feldkamp, R.F; Faust, J.A.; Cushman, A.J. J. Am. Chem. Soc. 1952, 74, 3831.
12. Some starting aminoalcohols were prepared according to literature procedures; i.e. 1-methyl-3-hydroxymethyl-hexamethyleneimine: Lee, D.L.; Morrow, C.J.; Rapoport, H.J. Org. Chem. 1974, 39, 893.
13. 1H NMR. All yields are given for isolated products and are unoptimized.
14. Rodriguez, M.; Linares, M.; Doulut, S.; Heitz, A.; Martinez, J. Tetrahedron Lett. 1991, 32, 923.
15. Fuson, R.C.; Zirkle, C.L. J. Am. Chem. Soc. 1948, 70, 2760.
16. Additional manuscripts, Young, J.R.; Walsh, T.F. et al. and Chu, L. et al., concerning the SAR of the 3-aryl group in non-peptide GnRH antagonists and the 6-position of quinolone GnRH antagonists are in preparation.
17. DeVita, R.J.; Goulet, M.T.; Wyvratt, M.J.; Fisher, M.H.; Lo, J.; Yang, Y.-T.; Cheng, K.; Smith, R.G. Bioorg. Med. Chem. Lett. 1999, 9, 2621.