US 2440649 А, 27.04.1948. GB 1108819 А, 03.04.1968. WO 01/90077 А1, 29.11.2001. Li Xun et al. Structure confirmation of L-iso-glutamine derivatives. Journal of Chemical Research, 2005, 2, с.94-95. F. Macovec et al. New glutamic and aspartic derivatives with potent CCK-antagonistic activity. Eur. J. Med. Chem.-Chim.Ther., 1986, т.21,1, с.9-20. U. Kuefner et al. Carboxypeptidase-Mediated Release of Methotrexate from Methotrexate -Peptides. Biochemistry, 1989, т.28, 5, с.2288-2297. W.E. Gaunt et al. CCLXIX. The Action of Phenyl Isocyanate on Insulin. II. Further Observation on the Chemistry of Insulin and its Phosphate-Lowering Power. The Biochemical Journal, 1936, том XXX, 10, с.1915-1926. D.L. Boger et al. Conformationally Restricted Analogues Designed for Selective Inhibition of GAR Tfase Versus Thymidylate Synthase or Dihydrofolate Reductase. Bioorganic & Medicinal Chemistry, 2000, т.8, с.5, с.1075-1086. I. Selmiciu, Zur Synthese der Nicotinoyl-p-aminobenzoyl-glutaminsaüre. Pharmazeutische Zentralhalle, 1951, т.90, 9, с.300-301. M. Bergmann et al. On Proteolytic Enzymes. VI. On the Specificity of Papain. J. Biol. Chem., 1935, т.111, с.225-244. F. Macovec et al. Structure-Antigastrin Activity Relationships of New (R)-4-Benzamido-5-oxopentanoic Acid Derivatives. J. Med. Chem., 1992, т.35, 1, с.28-38. D. J. Augeri et al. Potent and Selective Non-Cysteine-Containing Inhibitors of Protein Farnesyltransferase. J. Med. Chem., 1998, т.48, 22, с.4288-4300. С.J. Springer et al. Optimization of Alkylating Agent Prodrugs Derived from Phenol and Aniline Mustards: A New Clinical Candidate Prodrug (ZD2767) for Antibody-Directed Enzyme Prodrug Therapy (ADEPT). J. Med. Chem., 1995 т.38, 26, с.5051-5065. J.F. Kerwin et al, Hybrid Cholecystokinin (CCK) Antagonists: New Implications in the Design and Modification of CCK Antagonists. J. Med. Chem., 1989, т.32, 4, с.739-742. J.R. Piper et al. Syntheses of - and -Substituted Amides, Peptides, and Esters of Methotrexate and Their Evaluation as Inhibitors of Folate Metabolism. J. Med. Chem., 1982, т.25, 2, с.182-187. J. E. Martinelli et al. Methotrexate Analogues. 12. Synthesis and Biological Properties of Some Aza Homologues. J. Med. Chem., 1979, т.22, 7, с.869-874. DATABASE Chemical Abstract, 1965, 63: 14973f-h, C.H.Budeanu et al. Synthesis of anticancerous substances. IV. Obtention of Et N[N'-[p-bis(-chloroethyl)aminobenzoyl]--L-glutamyl]-p-aminobenzoate. 1964, Analete Stiint.Univ. "Al. I.Cuza" Isai, Sect. I. Chem. 10c(l), с.45-51. К. Sakyo et al. Methotrexate Matrix Metalloproteinase-1 (Collagenase). Inhibitory Effect of Methotrexate on Matrix Metalloproteinase-1 (Collagenase) Production by Synovial Fibroblasts. Oyo Yakuri, 1996, т.52, 6, с.451-457. С.Paal et al. Ueber die Einwirkung von Phenylisocyanat auf organische. Aminosäuren. Chem. Ber., 1903, т.3, с.3337-3345. DATABASE Beilstein, BRN 2600925. DATABASE Beilstein, BRN 2894932. WO 2005/060456 A2, 07.07.2005. WO 2005/058808 A1, 30.06.2005. WO 00/27808 A1, 18.05.2000. WO 01/83445 A1, 08.11.2001. RU 2189973 C2, 27.09.2002.
Имя заявителя:
ВАЙЕТ (US)
Изобретатели:
САМ Файк-Инг (US) ХАУ Дэвид Брайн (US) САБАТИНИ Джошуа Джеймс (US) КСЯНГ Джейсон Шаойюн (US) ФЕЙФАНТ Эрик (US) ТАМ Стив ЙикКай (US) СКОТНИКИ Джеральд Стэнли (US) МАНСУР Тарек Сахэйл (US)
Патентообладатели:
ВАЙЕТ (US)
Приоритетные данные:
11.07.2005 US 60/697,590
Реферат
Настоящее изобретение относится к новым соединениям формулы (I) или к их фармацевтически приемлемым солям, обладающим способностью модулировать активность металлопротеиназы, представляющей собой металлопротеиназу матрикса или аггреканазу, к фармацевтической композиции на их основе и к способу лечения остеоартрита.