Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1992-12-21
1995-03-28
Henley, III, Raymond J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514470, 514468, 514615, 514885, 549345, A61K 31335, A61K 3134, A61K 3116
Patent
active
054017670
ABSTRACT:
The present invention is directed to compounds which suppress immune responses and/or selectively inhibit complement. These compounds contain an aromatic ring and are substituted dihydrobenzofurans, spirobenzofuran-2(3H)-cycloalkanes, and their open chain intermediates. The compounds of the present invention, and the pharmaceutically acceptable salts thereof, interrupt the proteolytic processing of C5 to bioactive components, exhibit immunosuppressive activities, and have therapeutic utility in the amelioration of disease and disorders mediated by complement and/or immune activity.
REFERENCES:
patent: 3128286 (1964-04-01), Walker et al.
patent: 3518283 (1970-06-01), Brossi et al.
patent: 4035509 (1977-07-01), Nelson et al.
patent: 4229466 (1980-10-01), Miyazaki et al.
patent: 4263317 (1981-04-01), Martin et al.
patent: 4268516 (1981-05-01), Lombardino et al.
patent: 4301292 (1981-11-01), Martin et al.
patent: 4404221 (1983-09-01), Giamkowski et al.
patent: 4426380 (1984-01-01), Wenk et al.
patent: 4451462 (1984-05-01), Wenk et al.
patent: 4517311 (1985-05-01), Giamkowski et al.
patent: 4558043 (1985-12-01), Wenk et al.
patent: 4647677 (1987-03-01), Tamura et al.
patent: 4740519 (1988-04-01), Shroot et al.
patent: 4857516 (1989-08-01), Terao et al.
patent: 4863958 (1989-09-01), Belanger et al.
patent: 5173499 (1992-12-01), Sindelar et al.
Hong et al., 1979, "An anti-complementary agent, K-76 monocarboxylic acid: Its site and mechanism of inhibition of the complement activation cascade," J. Immunol., 122:2418.
Hong et al., 1981, "Inhibitory effect of K-76 monocarboxylic acid, an anticomplementary agent, on the C3b inactivator system," J. Immunol., 127:104.
Hong et al., 1981, "Simple methods for preparing EAC1, 4b, 2a, 3b, and EAC4b, 3b with human or guinea pig complement components using an anticomplementary agent, K-76 monocarboxylic acid," J. Immunol., 127:109.
Bumpers and Baum, 1983, "The effect of a novel C5 inhibitor (K-76 CONNa) on tumor cell chemotaxis," J. Lab. Clin. Med., 102:421.
Konno and Tsunifugi, 1983, "Induction of zymosan air pouch inflammation in rats and its characterization with reference to the effects of anticomplementary and anti-inflammatory agents," Dr. J. Pharmacol., 80:269.
Miyazaki et al., 1983, "Complement inhibitor, K-76 COOH," Farumashia (Japan) 19:912.
Ramm et al., 1983, "Size distribution and stability of the trans-membrane channels formed by complement complex C5b-9," Mol. Immunol., 20:155.
Hudig et al., 1984, "Inhibition of human lymphocyte natural cytotoxicity and antibody-dependent cell-mediated cytotoxicity by K-76 COONa, a reagent that blocks complement activity," J. Immunol., 133:408.
Miyazaki et al., 1984, "Effects of K-76 monocarboxylic acid, an anticomplementary agent, in various in vivo immunological reactions and on experimental glomerulonaphritis," Complement 1:134.
Rudelman et al., 1984, "The mechanism of cell-mediated cytotoxicity, II. K-76 COONa, which inhibits the activity of Factor I and CS, inhibits early events in cytotoxic T-lymphocyte-mediated cytolysis and in T-lymphocyte activation," Cell Immunol., 88:16.
Kanno and Tsurufugi, 1985, "Inhibitory effect of a novel anti-complementary agent, K-76 COONa, on the release of histamine induced by zymosan and compound 48/80," Jpn. J. Pharmacol., 38:116.
Redelman et al., 1986, "The induction of human T-cell growth factor receptor precedes the reduction of RNA and occurs in the presence of inhibitors of RNA synthesis," Cytometry 7:453.
Iida et al., 1987, "Effect of the anticomplementary agent, K-76 monocarboxylic acid on experimental immune complex glomerulonephritis in rats," Clin. Exp. Immunol., 67:130.
Miyazaki et al., 1980, "A complement inhibitor produced by Stachybotrys complementi, nov. sp. K-76, a new species of fungi imperfecti," Microbiol. Immunol., 24(11):1091.
Kaise et al., 1979, "Structure of K-76, a complement inhibitor produced by Stachybotrys complementi nov. sp. K-76," J. Chem. Soc. Chem. Commun., 726.
McMurry and Erion, 1985, "Stereoselective total synthesis of the complement inhibitor K-76," J. Am. Chem. Soc., 107:2712.
Corey and Das, 1982, "Total synthesis of the complement inhibitor K-76 in racemic form. Structural assignment to K-76 monocarboxylic acid," J. Am. Chem. Soc., 104:5551.
Spanevello et al., 1982, "Regioselective synthesis of the spiro-benzofuran unit, present in several natural products, by an intramolecular Michael cyclization," Syn. Commun. 16(7):749.
Sullivan et al., 1981, "Antimicrobial constituents of the sponge Siphonodictyon coralliphagum," Tetrahedron 37:979.
Dave et al., 1984, "A piscicidal chromanol and a chromenol from the brown alga Dictyopteris undulata," Heterocycles 22(10):2301.
Gerwick and Fenical, 1981, "Ichthyotoxic and cytotoxic metabolites of the tropical brown alga Stypopodium zonale (Lamouroux) papenfuss," J. Org. Chem., 46:22.
Brandt et al., 1972, "Structure and synthesis of crombenin, a natural spirocoumaranone," J. Chem. Soc. Chem. Commun., 392.
Antua et al., 1986, "Synthesis of Grisan," Tetrahedron 42(20):5637.
Kazlauskas et al., 1978, "New quinones from a dictyoceratid sponge," Aus. J. Chem., 31:2685.
Jackson and Short, 1937, "Anisoxide. Part I," J. Chem. Soc., 513.
Grove et al., 1952, "Griseofulvin. Part IV," J. Chem. Soc., 3977.
Oxford et al., 1935, "CXXXIX. Studies in the biochemistry of microorganisms. XLIV. Fulvic acid, a new crystalline yellow pigment, a metabolic product of P. griseofulvum dierckx, P. Flexuosum dale and P. Brefeldianum dodge," Biochem J., 29:1102.
Weinberg, 1981, "Principles of medicinal chemistry," 2d. Ed. Foye, W. O., ed., Lea and Febiger, Philadelphia, Pa. p. 813.
Closse et al., 1981, "2,3-dihydrobenzofuran-2-one: A new class of highly potent antinflammatory agents," J. Med. Chem., 24:1465.
Hammond et al., 1989, "2,3-dihydro-5-benzofuranols as antioxidant-based inhibitors of leukotriene biosynthesis," J. Med. Chem., 32:1006.
Kruse et al., 1981, "Synthesis of spiro[isobenzofuran-1(3H), 4'-piperidines] as potential central nervous system agents. 6. Synthesis, C-13 NMR, and biological evaluation of cis- and trans-4-amino-3'-arylspiro-[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives," J. Med. Chem. 24:617.
Narasimhan and Mali, 1983, "Synthesis of heterocyclic compounds involving aromatic lithiation reactions in the key step," Synthesis, 957.
Townsend and Bloom 1981, "Studies on methoxymethyl-directed metalation," Tet. Lett. 22:3923.
Ronald, 1975, "Methoxymethyl ethers, an activating group for rapid and regioselective metalation," Tet. Lett. 46:3973.
Lielbriedis and Gudriniece, 1968, "Diketone-based heterocyclic compounds," Latv. PSR Zinat. Akad. Vestis, Kim. Ser. 2:192.
Scholz et al., 1982, "Preparation and study of some transformations in 1(4H)-naphthalenone," Bol. Soc. Chil. Quim. 27(2):129.
Becker et al., 1983, "Chemotactic factors of inflammation," Trends Pharmacol. Sci., 4:223.
Becker, 1967, "The relationship of the structure of phosphonate esters to their ability to inhibit chymotrypsin, trypsin, acetylcholinesterase and C'ia," Biochim. Biophys. Acta., 147:289.
Bradbury and Sindelar, 1989, "Synthesis of 4,7-disubstituted spirobenzofuran-2(3H)-cyclohexanes," J. Heterocyclic Chem., 26:1827.
Bult and Herman, 1983, "Inflammatory mediators released by complement-derived peptides," Agents and Actions 13(5/6):405.
Burge et al., 1978, "Inhibition of the alternative pathway of complement by gold sodium thiomalate in vitro," J. Immunol., 120(5):1625.
Cavarocchi et al., 1986, "Oxygen free radical generation during cardiopulmonary bypass: correlation with complement activation," Circulation 74(suppl.III):130.
Crawford et al., 1972, "Metalation of limonene. A novel method for the synthesis of bisabolane sesquiterpenes," J. Am. Chem. Soc., 94:4298.
Djura and Sargent, 1983, "The structure of isopannarin," Aust. J. Chem., 36:1057.
Eisen, 1979, "Cell-mediated hypersensitivity and immunity," Immunology Ch. 20, Harper and Row, Hagerstown, Md., p. 558.
Eisen et al., 1974, "Complement," Immunology Ch. 18, Harper and Row, Publishers Inc., Hagerstown, Md., p. 512.
Fugi et al., 1979, "Hard acid and soft nucleophile syste
Bradbury Barton J.
Ip Stephen H.
Kaufman Teodoro
Marsh, Jr. Henry C.
Sindelar Robert D.
Criares T. J.
Henley III Raymond J.
T Cell Sciences, Inc.
The University of Mississippi
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