Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2005-06-14
2005-06-14
Aulakh, Charanjit S. (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C549S336000, C546S195000, C546S197000, C548S526000, C514S319000, C514S321000, C514S422000
Reexamination Certificate
active
06906098
ABSTRACT:
Disclosed herein are mixed steroidal tetraoxanes having the following structural formula 1wherein n is 0, 1, 2, or 3; R is H; ethanoyl, propanoyl, or benzoyl; R1 is H, methyl, ethyl, or isopropyl; R2 is H, methyl, or ethyl; R3 is H, methyl, or ethyl; R4 is H, methyl, ethyl, tert-butyl, phenyl, p-hydroxyphenyl, p-methoxyphenyl, or p-nitrophenyl, orwherein Y is a C1-C4straight or branched-chain alkoxy, orwherein W is N, R5 is hydrogen, methyl, ethyl, n-propyl, isopropyl, or methyl ethanoate 2-yl, and R6 is hydrogen, methyl, ethyl, or n-propyl, or R5 and R6 are part of a pyrrolidine or piperidine ring; X is a C1-C4straight or branched-chain alkoxy, a primary amino, a N-alkylamino wherein the alkyl is a straight-chain alkyl groups containing from 1 to 4 carbon atoms, methyl ethanoate-2-yl, N-phenylamino, p-nitrophenyl, N,N-dimethylamino, N,N-diethylamino, N,N-di(n-propyl)amino, N-pyrrolidino, or N-piperidino as single compounds, and any mixture of all possible stereoisomers at C(4″). n may be 0, 1, 2, or 3, and methods of making and using thereof. As disclosed herein, the mixed steroidal tetraoxanes of the present invention exhibit antimalarial, antibacterial, and antiproliferative activity. Thus, as disclosed herein, the mixed steroidal tetraoxanes of the present invention may be used to treat, prevent, or inhibit malaria, bacterial infections, and diseases and disorders associated with cell proliferation in a subject.
REFERENCES:
patent: 3003000 (1961-10-01), Milas
patent: 3116300 (1963-12-01), Braunwarth et al.
patent: 3879420 (1975-04-01), Story et al.
patent: 3880882 (1975-04-01), Story et al.
patent: 3925417 (1975-12-01), Story et al.
patent: 3925421 (1975-12-01), Story et al.
patent: 3960897 (1976-06-01), Story et al.
patent: 5578637 (1996-11-01), Lai et al.
patent: 6054625 (2000-04-01), Frenkel et al.
patent: 1175415 (1959-03-01), None
patent: 842922 (1960-07-01), None
patent: 2000-229965 (2000-08-01), None
patent: 2003104967 (2003-04-01), None
patent: WO 93/07119 (1993-04-01), None
Solaja, B. et al.: Mixed steroidal 1, 2,4,5-tetraoxanes: Antimalarial and antibacterial activity. J. Med. Chem. vol. 45, pp. 3331-3336, 2002.
Bertrand, et al., “Mass Spectrometry of Cyclic Organic Peroxides”, Cyclic Organic Peroxides, vol. 33, No. 5, pp. 1931-1934, (1968).
Caglioti, et al., “Oxidation of N-Alkyl-N'-Tosylhydrazines to Hydroperoxides”, Tetrahedron, vol. 34, pp. 135-139 (1978).
Cremer, et al., “A General Definition of Ring Puckering Corrdinates”, Journal of the American Chemical Society, 97:6, pp. 1354-1358 (1975).
Dong, et al., “Synthesis and Antimalarial Activity of 11 Dispiro-1,2,4,5-tetraoxane Analogues of WR 148999. 7,8,15,16-Tetraoxadispiro [5.2.5.2] hexadecanes Substituted at the 1 and 10 Positions with Unsaturated and Polar Functional Groups”, J. Med. Chem. (1999), 42, pp. 1477-1480.
Jefford, et al., “A New Method for the Synthesis of gem-Dihydroperoxides”, Synthetic Communications, 20(17), pp. 2589-2596 (1990).
Jefford, et al., “Efficient Preparation of 1, 2, 3, 5-Tetroxanes from Bis(trimethylsilyl) Peroxide and Carbonyl Compounds”, Communications, pp. 391-393 (1988).
Jefford, et al, “The Structure and Antimalarial Activity of Some 1,2,4-Trioxanes, 1,2,4,5-Tetroxanes, and Bicyclic Endoperoxides. Implications for the Mode of Action”, Heterocycles, vol. 52, No. 3, pp. 1345-1352 (2000).
Kharasch, et al., “Structure of Peroxides Derived from Cyclohexanone and Hydrogen Peroxide”, Institute of Organic Chemistry, the University of Chicago, vol. 23, pp. 1322-1326 (1958).
Kim, et al, Synthesis and Antimalarial Activity of Novel Medium-Sized 1,2,4,5-Tetraoxacycloalkanes, J. Med. Chem. (2001), 33, pp. 2357-2361.
Kim, et al, Synthetic methods for unsymmetrically-substituted 1,2,4,5-tetraoxanes and of 1,2,4,5,7-pentoxocanes, J. Chem. Soc., Perkin Trans 1, (1999), pp. 1867-1870.
Ledal, “Mass Spectrometric Investigations of Organic Peroxides”, Tetrahedron Letters No. 41, pp. 3661-3664 (1969).
McCullough, et al., “Ketone-derived Peroxides, Part 1, Synthetic Methods”, J. Chem. Research (S), 1980, 34.
McCullough, et al., “Methyl-Substituted Dispiro-1,2,4,5-tetraoxanes: Corelations of Structural Studies with Antimalarial Activity”, J. Med. Chem, 2000, 43, pp. 1246-1249.
McCullough, et al., “The synthesis and crystal structure analysis of novel macrocyclic peroxides”, Tetrahedron Letters 42 (2001) pp. 5529-5532.
Milas, et al., “Studies in Organic Peroxides. XXIV. Preparation, Separation and Identification of Peroxides Derived from Diethyl Ketone and Hydrogen Peroxide”, The Department of Chemistry, Massachusetts Institute of Technology, pp. 3361-3363 (1959).
Milas, et al., “Studies in Organic Peroxides. XXV. Preparation, Separation and Identification of Peroxides Derived from Methyl Ethyl Ketone and Hydrogen Peroxide”, The Department of Chemistry, Massachusetts Institute of Technology, pp. 5824-5826, vol. 81 (1959).
Milas, et al., “Studies in Organic Peroxides. XXVI. Organic Peroxides Derived from Acetone and Hydrogen Peroxide”, The Department of Chemistry, Massachusetts Institute of Technology, pp. 6461-6462, vol. 81 (1959).
Nonami, et al., “Synthesis, crystal structure and antimalarial activity of functionalized spiro-1,2,4,5-tetraoxacycloalkanes from unsaturated hydroperoxy peracetals”, Tetrahedron Letters 41 (2000) pp. 4681-4684.
Opsenica, et al., “Cholic Acid Derivatives as 1,2,4,5-Tetraoxane Carriers: Structure and Antimalarial and Antiproliferative Activity”, J. Med. Chem. (2000), 43, pp. 3274-3282.
Robertson, et al., “Diphenylmethyl Bishydroperoxide. An Anomalous Product from the Ozonolysis of Tetraphenylethylene” The Journal of Organic Chemistry, vol. 35, No. 2, pp. 545-547 (1970).
Sanderson, et al., “Macrocycles. The Synthesis and Thermal Decomposition of Some Disubstituted Dicyclohexylidene Diperoxides”, Communications, pp. 159-161 (1975).
Todorovic, et al., “Steriodal geminal dehydroperoxides and 1,2,4,5-tetraoxanes: Structure determination and their antimalarial activity”, Steroids, (1996), vol. 61, pp. 688-696.
Tsuchiya, et al., “Synthesis, Crystal Structure and Anti-Malarial Activity of Novel Spiro-1,2,4,5-Tetraoxacycloalkanes”, Tetrahedron Letters 40 (1999) pp. 4077-4080.
Velluz, et al., Bishydroperoxydes steroids. II—Preparation et proprietes, Memoires Presentes A La Societe Chimique, pp. 879-882, (1957).
Vennerstrom, et al., “Synthesis and Antimalarial Activity of Sixteen Dispiro-1,2,4,5-tetraoxanes: Alkyl-Substituted 7,8,15,16-Tetraoxadispiro [5.2.5.2] hexadecanes”, J. Med. Chem. (2000), 43, pp. 2753-2758.
Vennerstrom, et al., “Dispiro-1,2,4,5-tetraoxanes: A New Class of Antimalarial Peroxides”, J. Med. Chem. (1992), 35, pp. 3023-3027.
Warnant, et al., “No. 39—Bis-hydroperoxydes de quelques ceto-steroides”, Memoires Presentes A La Societe Chimique, pp. 331-332, (1956).
2000 American Chemical Society, J. Med. Chem., Opsenica jm000952f Supporting Info, pp. 1-13.
International Search Report (Form PCT/ISA/210) issued for PCT/US03/03516 (Feb. 13, 2004).
Kyle Dennis E.
Milhous Wilbur K.
Opsenica Dejan M.
Pocsfalvi Gabriella
Solaja Bogdan
Arwine Elizabeth
Aulakh Charanjit S.
The United States of America as represented by the Secretary of
LandOfFree
Mixed steroidal 1,2,4,5-tetraoxane compounds and methods of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Mixed steroidal 1,2,4,5-tetraoxane compounds and methods of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Mixed steroidal 1,2,4,5-tetraoxane compounds and methods of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3518182