Two Of The Cyclos Share At Least Three Ring Members Or A Ring Member Is Shared By Three Of The Cyclos (e.g., Bridged, Peri-fused, Etc.) Patents (Class 540/456)
Abstract: This invention provides non-immunosuppressive rapamycin 29-enols, which are useful as neurotrophic agents, in the treatment of solid tumors, and vascular disease.
Abstract: The invention relates to benzoquinone ansamycin analogs useful for the treatment of cancer and other diseases or conditions characterized by undesired cellular proliferation or hyperproliferation. Therapies involving the administration of such benzoquinone ansamycin analogs, optionally in combination with an inhibitor of an HSP90 client protein, are useful to treat cancer and non-cancerous disease conditions.
Type:
Application
Filed:
August 5, 2002
Publication date:
June 19, 2003
Inventors:
Daniel Santi, David C. Myles, Zong-Qiang Tian, C. Richard Hutchinson, Robert Johnson, Yi-Qing Zhou, Li Feng
Abstract: This invention provides non-immunosuppressive rapamycin dialdehydes, which are useful as neurotrophic agents, in the treatment of solid tumors, and vascular disease.
Abstract: The present invention relates to novel polyketides, host cells that produce the novel compounds, and methods fort their use. The compounds of the present invention are cyclic polyketides (also referred to as a “macrolides” or “macrolactones”) that include
as part of their structure and bind to a FK binding protein wherein R4 and R5 are each selected from the group consisting of hydrogen, methyl, ethyl, and methoxy, provided that at least one of R4 and R5 is hydrogen, methyl, or ethyl. As will be explained in greater detail below, the compounds of the present invention have properties such as favorable P450 enzyme activity profiles that are desirable for use of these compounds as drugs.
Type:
Grant
Filed:
May 10, 2001
Date of Patent:
May 27, 2003
Assignee:
Kosan Biosciences, Inc.
Inventors:
Daniel Chu, Maria Fardis, Chaitan Khosla, Christopher Reeves, Daniel Santi, Andreas Schirmer
Abstract: Group A streptogramin derivatives of general formula (I) in which:
R1 represents a halogen atom or an azido or thiocyanato radical,
R2 represents a hydrogen atom or a methyl or ethyl radical,
R3 represents a hydrogen atom, or the residue of an aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic or heterocyclylaliphatic ester which may be substituted, and
the bond - - - represents a single bond (stereochemistry 27R) or a double bond,
as well as its salts when they exist.
Type:
Grant
Filed:
June 30, 2000
Date of Patent:
May 27, 2003
Assignee:
Aventis Pharma S.A.
Inventors:
Daniel Achard, Eric Bacque, Jean-Claude Barriere, Jean Bouquerel, Pascal Desmazeau, Serge Grisoni, Jean-Pierre Leconte, Yves Ribeill, Baptiste Ronan
Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.
Type:
Grant
Filed:
January 9, 2001
Date of Patent:
May 20, 2003
Assignee:
Merck & Co., Inc.
Inventors:
S. Jane deSolms, Gerald E. Stokker, Anthony W. Shaw
Abstract: The present invention is directed to a process for the preparation of a compound of formula (X-a)
or a pharmaceutically acceptable salt form thereof,
wherein:
R1 is selected from the group consisting of:
C1-5 alkyl substituted with 0-5 R1a,
—(CH2)r—C3-10 cycloalkyl substituted with 0-5 R1a, and
—(CH2)r-aryl substituted with 0-5 R1a.
Compounds of Formula (X-a) are macrocyclic molecules containing anti-succinate residues which inhibit metalloproteinases such as aggrecanase, and the production of tumor necrosis factor (TNF). The anti-succinates are formed by an Ireland Claisen rearrangement of a silyl ketene acetal which proceeds with high stereoselectivity.
Type:
Grant
Filed:
July 31, 2001
Date of Patent:
May 13, 2003
Inventors:
Roberta L. Dorow, Silvio Campagna, Pasquale N. Confalone, Fuqiang Jin, Zhe Wang
Abstract: The invention provides compounds of formula
as described in the claims, or an optical isomer, diastereomer or enantiomer thereof, or a pharmaceutically-acceptable salt, or biohydrolyzable amide, ester, or imide thereof are useful as inhibitors of metalloproteases.
Also disclosed are pharmaceutical compositions and methods of treating diseases, disorders and conditions characterized by metalloprotease activity using these compounds or the pharmaceutical compositions containing them.
Type:
Grant
Filed:
November 6, 2000
Date of Patent:
April 8, 2003
Assignee:
The Procter & Gamble Company
Inventors:
Biswanath De, Stanislaw Pikul, Menyan Cheng, Neil Gregory Almstead, Randall Stryker Matthews, Michael George Natchus, Yetunde Olabisi Taiwo
Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.
Type:
Grant
Filed:
April 6, 2001
Date of Patent:
March 18, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Diem N. Nguyen, Craig A. Stump, Theresa M. Williams
Abstract: The invention provides novel polyketide compounds having desired bioactivity, including neuroregenerative activity without immunosuppressive activity, and methods of making and using these compounds.
Type:
Application
Filed:
March 15, 2002
Publication date:
March 6, 2003
Inventors:
Thomas C. Bruice, Helgi Adalsteinsson, Kalju Kahn
Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.
Type:
Grant
Filed:
January 9, 2001
Date of Patent:
February 25, 2003
Assignee:
Merck & Co., Inc.
Inventors:
S. Jane deSolms, Suzanne C. MacTough, Anthony W. Shaw
Abstract: The synthesis of deuterated analogues of rapamycin is disclosed together with a method for use for inducing immunosupression and in the treatment of transplantation rejection, graft vs host disease, autoimmune diseases, diseases of inflammation leukemia/lymphoma, solid tumors, fungal infections, hyperproliferative vascular disorders. Also described is a method for the synthesis of water soluble deuteratred rapamycin compounds and their use as described above.
Type:
Grant
Filed:
November 16, 2001
Date of Patent:
January 7, 2003
Assignee:
Isotechnika, Inc.
Inventors:
Selvaraj Naicker, Randall W. Yatscoff, Robert T. Foster
Abstract: Helical oligomer and polymer compositions that form nanotubes are described. The compositions comprise a plurality of aromatic substituents linked by at least one amide group. The compositions have a curved backbone due to intramolecular hydrogen bonds that rigidify the amide linkage of each amide group to each aromatic substituent and due to an interaction between the aromatic substituents such that the curved backbone is stabilized. The helical compositions are formed by ridigifying the amide group, which is flanked on each side by the aromatic substituents, by introducing intramolecular hydrogen bonds into a linkage between the amide group and each aromatic substituent such that the compositions fold into a helical shape when the amide linkages are meta to each other.
Abstract: The present invention relates to a method for separating a lactone-containing high-molecular weight compound having an alkyl group as its side chain from a lactone-containing high-molecular weight compound having an alkenyl group as its side chain by using a sulfonic acid group-containing cation exchange resin pretreated with silver ions.
Abstract: This invention concerns derivatives of rapamycin and their antifungal uses. Also disclosed are materials and methods relevant to the identification of non-immunosuppressive anti-fungal rapamycin derivatives.
Type:
Application
Filed:
July 10, 2001
Publication date:
November 7, 2002
Inventors:
Dennis A. Holt, Terence P. Keenan, Timothy P. Clackson, Leonard Rozamus, Wu Yang, Michael Z. Gilman
Abstract: Provided are rapamycin conjugates which are useful as immunogenic molecules for the generation of antibodies specific for rapamycin, for measuring levels of rapamycin or derivatives thereof; for isolating rapamycin binding proteins; and detecting antibodies specific for rapamycin or derivatives thereof. This invention also provides a rapamycin specific monoclonal antibody.
Type:
Application
Filed:
April 18, 2002
Publication date:
October 17, 2002
Inventors:
Katherine L. Molnar-Kimber, Craig E. Caufield, Timothy D. Ocain
Abstract: This invention provides a process for purifying a cyclosporin, e.g. cyclosporin A, or a macrolide, to a high degree of purity on a large scale. In another aspect this invention provides a bulk quantity of cyclosporin A with an impurity level of less than about 0.7%, e.g. about 0.5%, and compositions thereof.
Type:
Application
Filed:
October 29, 2001
Publication date:
September 12, 2002
Inventors:
Peter Fuenfschilling, Berthold Schenkel
Abstract: Laulimalide compounds, intermediates thereto and methods for their preparation, and methods for their use in the treatment of diseases characterized by cellular hyperproliferation.
Abstract: The present invention is directed to macrocyclic compounds which inhibit prenyl-protein transferase (FTase) and the prenylation of the oncogene protein Ras. The invention is further directed to chemothera-peutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.
Type:
Grant
Filed:
September 7, 2000
Date of Patent:
August 27, 2002
Assignee:
Merck & Co., Inc.
Inventors:
Ian M. Bell, Douglas C. Beshore, Steven N. Gallicchio, C. Blair Zartman
Abstract: Novel derivatives of rapamycin, particularly 9-deoxo-rapamycins, 26-dihydro-rapamycins, and 40-O-substituted and 28,40-O,O-disubstituted rapamycins. are found to have pharmaceutical utility, particularly as immunosuppressants.
Abstract: This invention provides ethers of 7-desmethylrapamycin which are useful in inducing immunosuppression and in the treatment of transplantation rejection, autoimmune diseases, solid tumors, fungal infections, and vascular disease.
Abstract: This invention provide pegylated hydroxyesters of rapamycin which are useful in inducing immunosuppression and in the treatment of transplantation rejection, autoimmune diseases, solid tumors, fungal infections, and vascular disease.
Abstract: 33-Epichloro-33-desoxyascomycin of formula I
and various tautomeric or forms thereof, in crystalline form, such as Form A and Form B.
Their preparation involves appropriately converting amorphous compound of formula I, or compound of formula I in other than Form A, or compound of formula I in other than Form B, respectively, from a solution thereof under crystallization-inducing conditions or conditions inducing preferential crystallization of Form A or B, respectively.
Such crystals are particularly indicated for use in the preparation of topical galenical forms of the compound for pharmaceutical use, e.g. creams, emulsions and ointments.
Type:
Grant
Filed:
October 17, 2000
Date of Patent:
July 23, 2002
Assignee:
Novartis AG
Inventors:
Cornelia Dosenbach, Maximilian Grassberger, Otto Hartmann, Amarylla Horvath, Jean-Paul Mutz, Gerhard Penn, Sabine Pfeffer, Dierk Wieckhusen
Abstract: The present invention is directed to peptidomimetic macrocyclic compounds of the formula A:
wherein W is a heterocycle, V is a heterocycle or aryl moiety and Z1 is a suitably substituted aryl or heterocycle moiety. The instant compounds inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.
Type:
Grant
Filed:
January 9, 2001
Date of Patent:
July 2, 2002
Inventors:
S. Jane deSolms, Suzanne C. MacTough, Anthony W. Shaw
Abstract: This invention provides 1-oxorapamycins, which are useful in inducing immunosuppression, as a neurotrophic agent, and in the treatment of transplantation rejection, autoimmune diseases, solid tumors, fungal infections, and vascular disease.
Abstract: This invention provides hydroxyesters of 7-desmethylrapamycin which are useful in inducing immunosuppression and in the treatment of transplantation rejection, autoimmune diseases, solid tumors, fungal infections, and vascular disease.
Abstract: Novel thiazolyl peptide compounds useful for the treatment of serious bacterial infections, and pharmaceutical compositions thereof are provided.
Type:
Application
Filed:
August 13, 2001
Publication date:
May 30, 2002
Inventors:
B. Narasimhulu Naidu, Wenying Li, Kin S. Lam, Margaret E. Sorenson, John A. Wichtowski, Timothy P. Connolly, Yasutsugu Ueda, Joanne J. Bronson, Yunhui Zhang, Oak K. Kim
Abstract: This invention provides ethers of 7-desmethylrapamycin which are useful in inducing immunosuppression and in the treatment of transplantation rejection, autoimmune diseases, solid tumors, fungal infections, and vascular disease.
Abstract: This invention provides 1-oxorapamycins, which are useful in inducing immunosuppression, as a neurotrophic agent, and in the treatment of transplantation rejection, autoimmune diseases, solid tumors, fungal infections, and vascular disease.
Abstract: This invention provides hydroxyesters of 7-desmethylrapamycin which are useful in inducing immunosuppression and in the treatment of transplantation rejection, autoimmune diseases, solid tumors, fungal infections, and vascular disease.
Abstract: This invention provide pegylated hydroxyesters of rapamycin which are useful in inducing immunosuppression and in the treatment of transplantation rejection, autoimmune diseases, solid tumors, fungal infections, and vascular disease.
Abstract: A method of making a synthetic nucleic acid sequence comprises providing a starting nucleic acid sequence, which optionally encodes an amino acid sequence, and determining the predicted &Dgr;Gfolding of the sequence. The starting nucleic acid sequence can be a naturally occurring sequence or a non-naturally occurring sequence. The starting nucleic acid sequence is modified by replacing at least one codon from the starting nucleic acid sequence with a different corresponding codon to provide a modified nucleic acid sequence. As used herein, a “different corresponding codon” refers to a codon which does not have the identical nucleotide sequence, but which encodes the identical amino acid. The predicted &Dgr;Gfolding of the modified nucleic acid sequence is determined and compared with the &Dgr;Gfolding of the starting nucleic acid sequence.
Abstract: A combination of a compound of the somatostatin class and a rapamycin macrolide is useful for the prevention or treatment of cell hyperproliferation.
Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.
Type:
Grant
Filed:
June 29, 1999
Date of Patent:
March 19, 2002
Assignee:
Merck & Co., Inc.
Inventors:
Neville J. Anthony, Ian M. Bell, Douglas C. Beshore, Terrence M. Ciccarone, S. Jane de Solms, Christopher J. Dinsmore, Gerald E. Stokker
Abstract: A mixture comprising a poly-ene macrolide and an antioxidant. Preferably, the poly-ene macrolide is rapamycin and the antioxidant is 2,6-di-tert.-butyl-4-methylphenol. The presence of the antioxidant improves the stability of the poly-ene macrolide to oxidation.
Type:
Application
Filed:
May 29, 2001
Publication date:
March 14, 2002
Inventors:
Francois Navarro, Samuel Petit, Guy Stone
Abstract: The synthesis of deuterated analogues of rapamycin is disclosed together with a method for use for inducing immunosupression and in the treatment of transplantation rejection, graft vs host disease, autoimmune diseases, diseases of inflammation leukemia/lymphoma, solid tumors, fungal infections, hyperproliferative vascular disorders. Also described is a method for the synthesis of water soluble deuteratred rapamycin compounds and their use as described above.
Type:
Application
Filed:
November 16, 2001
Publication date:
March 7, 2002
Inventors:
Selvaraj Naicker, Randall W. Yatscoff, Robert T. Foster
Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.
Abstract: Monoclonal antibodies to rapamycin and to 40-O-alkylated derivatives of rapamycin are provided, together with novel haptens, immunogenic conjugates, and processes for making them and assay kits for using them.
Type:
Application
Filed:
January 9, 2001
Publication date:
February 21, 2002
Inventors:
Richard Sedrani, Valerie Quesniaux Ryffel
Abstract: The synthesis of deuterated analogues of rapamycin is disclosed together with a method for use for inducing immunosupression and in the treatment of transplantation rejection, graft vs host disease, autoimmune diseases, diseases of inflammation leukemia/lymphoma, solid tumors, fungal infections, hyperproliferative vascular disorders. Also described is a method for the synthesis of water soluble deuteratred rapamycin compounds and their use as described above.
Type:
Grant
Filed:
July 6, 1999
Date of Patent:
January 29, 2002
Assignee:
Isotechnika, Inc.
Inventors:
Selvaraj Naicker, Randall W. Yatscoff, Robert T. Foster
Abstract: Host cells comprising recombinant vectors encoding the FK-520 polyketide synthase and FK-520 modification enzymes can be used to produce the FK-520 polyketide. Recombinant DNA constructs comprising one or more FK-520 polyketide synthase domains, modules, open reading frames, and variants thereof can be used to produce recombinant polyketide synthases and a variety of different polyketides with application as pharmaceutical and veterinary products.
Type:
Application
Filed:
April 3, 2001
Publication date:
January 24, 2002
Inventors:
Christopher Reeves, Daniel Chu, Chaitan Khosla, Daniel Santi, Kai Wu
Abstract: Monoclonal antibodies to rapamycin and to 40-O-alkylated derivatives of rapamycin are provided, together with novel haptens, immunogenic conjugates, and processes for making them and assay kits for using them.
Abstract: The present invention provides a process for the preparation and purification of thiol-containing maytansinoids comprising the steps of: (1) reductive hydrolysis of a maytansinoid C-3 ester with a reducing agent selected from the group consisting lithium trimethoxyaluminum hydride (LiAl(OMe)3H), lithium triethoxyaluminum hydride (LiAl(OEt)3H), lithium tripropoxyaluminum hydride (LiAl(OPr)3H), sodium trimethoxyaluminum hydride (NaAl(OMe)3H), sodium triethoxyaluminum hydride (NaAl(OEt)3H) and sodium tripropoxyaluminum hydride (NaAl(OPr)3H) to yield a maytansinol; (2) purifying the maytansinol to remove side products when present; (3) esterifying the purified maytansinol with a carboxylic acid to yield a mixture of an L- and a D-aminoacyl ester of maytansinol; (4) separating the L-aminoacyl ester of maytansinol from the reaction mixture in (3); (5) reducing the L-aminoacyl ester of maytansinol to yield a thiol-containing maytansinoid; and (6) purifying the thiol-containing maytansinoid.
Type:
Grant
Filed:
August 18, 2000
Date of Patent:
December 25, 2001
Assignee:
Immunogen, Inc.
Inventors:
Ravi Vankeepuram Jagannatha Chari, Wayne Charles Widdison
Abstract: This invention provides novel water soluble pegylated esters of rapamycin, having the general structure:
wherein n is an integer from about 5 to about 450, as well as pharmaceutical compositions containing these compounds and methods for their use as immunosuppressive, anti-inflammatory, antifungal, antiproliferative and antitumor agents.
Type:
Grant
Filed:
August 16, 2000
Date of Patent:
December 18, 2001
Assignee:
American Home Products Corporation
Inventors:
Tianmin Zhu, Syed M. Shah, Richard W. Saunders
Abstract: Rapamycin derivatives; pharmaceutical compositions comprising such rapamycin derivatives and pharmaceutically acceptable carriers or diluents; and methods of using such derivatives to inhibit pathogenic fungi growth, inhibit immunosuppression or treat carcinogenic tumors are disclosed.
Type:
Grant
Filed:
July 23, 1999
Date of Patent:
October 23, 2001
Assignee:
SmithKline Beecham Corporation
Inventors:
Dennis Alan Holt, Juan Ignacio Luengo, Leonard Walter Rozamus, Jr.