Abstract: Combinatorial libraries of polyketides can be obtained by suitable manipulation of a host modular polyketide synthase gene cluster such as that which encodes the PKS for erythromycin. The combinatorial library is useful as a source of pharmaceutically active compounds. In addition, novel polyketides and antibiotics are prepared using this method.
Type:
Grant
Filed:
May 16, 2001
Date of Patent:
August 9, 2005
Assignees:
Kosan Biosciences, The Board of Trustees of the Leland Stanford Junior University
Inventors:
Chaitan Khosla, Gary Ashley, Camilla M. Kao, Robert McDaniel
Abstract: The invention provides a stable ectoparasiticidal aqueous suspension formulation of a spinosyn, comprising the spinosyn, or a physiologically acceptable derivative or salt thereof, milled to an average particle size of 1 to 15 microns, a surfactant in an amount effective to facilitate wetting the milled particles; a dispersant in an amount that forms a spinosyn;dispersant weight ration of from 3:1 to 1:5; and water. It also provides a method of controlling an ectoparasite infestation on a small ruminant or companion animal comprising administering an effective amount of such an aqueous suspension formulation.
Type:
Grant
Filed:
August 2, 2000
Date of Patent:
August 9, 2005
Assignee:
Eli Lilly and Company
Inventors:
William Webster Thompson, Joseph Raymond Winkle
Abstract: Synergistic combinations of a squalene epoxidase inhibitor such as terbinafine and a macrolide T-cell immunomodulator or immunosuppressant such as 33-epichloro, 33-desoxyascomycin are provided, which are useful in particular in the treatment of diseases involving fungal or suspected fungal infection, for immunomodulation or immunosuppression in conditions in which fungal or suspected fungal colonisation of e.g. the skin plays a role, such as atopic dermatitis and seborrhoeic dermatitis, and in situations of fungal resistance.
Type:
Grant
Filed:
February 16, 2001
Date of Patent:
July 19, 2005
Assignee:
Novartis AG
Inventors:
Neil Stewart Ryder, Friedrich Karl Mayer
Abstract: An improved process for the preparation of the antiparasitic compound 25-cyclohexyl-22,23-dihydro-5-hydroxyiminoavermectin B1 monosaccharide from doramectine and intermediates therefor and crystalline solvates thereof.
Abstract: A novel family of cyclic polyene natural products isolated from marine actinomycete strain CNQ140 is provided. This novel strain of actinomycetes was obtained from a previously unstudied population of marine actinomycetes that reside in sediments off La Jolla, Calif. Compounds derived from strain CNQ140 have been characterized as having a cyclic polyene-polyol structure; a molecular weight from about 996 to about 1010 in the core ring structure; and at least 58 carbons and at least 14 oxygens. The invention compounds have antitumor and/or anti-microbial activity.
Type:
Application
Filed:
June 21, 2004
Publication date:
December 30, 2004
Applicant:
The Regents of the University of California
Inventors:
William H. Fenical, Paul R. Jensen, Hak Cheol Kwon
Abstract: A description is given of compounds of the formula which in the 4″-position has the (S)-configuration and wherein R1 is C1-C12alkyl, C3-C8cycloalkyl; or C2-C12alkenyl; R2 is hydrogen, optionally substituted C1-C12alkyl or optionally substituted C2-C12alkenyl; R3 is C1-C12alkyl, optionally substituted C1-C12alkyl, optionally substituted C1-C12alkoxy-C1-C12alkyl, optionally substituted C3-C12cycloalkyl, optionally substituted C2-C12alkenyl; optionally substituted C4-C12cycloalkenyl, optionally substituted C2-C12alkynyl; or R2 and R3 together are a three- to seven-membered alkylene or four- to seven-membered alkenylene bridge in each of which a CH2 group may have been replaced by O, S or NR4; X is O or S; R4 is C1-C8alkyl, C3-C8cycloalkyl, C2-C8alkenyl, C2-C8alkynyl, benzyl or C(═O)—R5; R5 is for example H, OH, SH, C1-C12alkyl, C2-C8alkenyl, C2-C8alkynylyl or C1-C12haloalkyl; and, where appropriate, E/Z isomers, mixtures of E/Z isomers and/or tautomers thereof, in each case in free form or in sa
Abstract: The present invention relates to methods for producing novel spinosyn derivatives which are substituted with a 1-hydroxy-ethyl radical in the C-21 position and to novel spinosyn derivatives of this type per se and to their use for producing novel spinosyns.
Type:
Application
Filed:
July 9, 2004
Publication date:
December 2, 2004
Inventors:
Peter Jeschke, Gunther Eberz, Rita Frode, Volker Mohrle, Robert Velten
Abstract: There are described novel 5-O-mycaminosyltylonide derivatives and pharmaceutically acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier. Also described are a method for treating bacterial infections by administering to an animal a pharmaceutical composition containing a therapeutically-effective amount of a compound of the invention, and processes for the preparation of such compounds.
Type:
Application
Filed:
March 9, 2004
Publication date:
November 25, 2004
Inventors:
Ly Tam Phan, Nha Vo, Yat Sun Or, Yao-Ling Qiu, Ying Hou
Abstract: The present invention is to provide a process for producing a 2′-O-acetyl-4″-O-formyl-8,9-anhydroerythromycin A 6,9-hemiketal compound 4, and it provide a process for producing an erythromycin compound which comprises reacting a formylating agent with a 2′-O-acetylerythromycin A compound 2 to obtain 2′-O-acetyl-4″-O-formylerythromycin A compound 3, then, acting an acid on Compound 3 to subject to hemiketalation, and then adding an aqueous basic solution in an aqueous solution to precipitate Compound 4 as free crystals.
Abstract: The present invention is to provide a process for producing an erythromycin compound by subjecting a 2′-O-acetyl-4″-O-formyl-11-oxo-8,9-anhydroerythromycin A 6,9-hemiketal compound 1 to alkylation, which comprises reacting Compound 1 with an alkylating agent in the presence of a base in a mixed solvent of 0.18 to 1.05 equivalent of water based on Compound 1 and an organic solvent to give a 2′-O-acetyl-4″-O-formyl-11-oxo-12-alkoxy-8,9-anhydroerythromycin A 6,9-hemiketal compound 3.
Abstract: The present invention provides two new classes of polyene macrolide amide derivatives useful for treating or preventing fungal infections. The new polyene macrolide amide derivatives exhibit antifungal activity and are more water-soluble than conventional polyene antibiotics, such as amphotericin B and amphotericin B methyl ester.
Type:
Application
Filed:
October 23, 2003
Publication date:
July 15, 2004
Applicant:
Micrologix Biotech Inc.
Inventors:
Conway C. Chang, Binh T. Dang, Christopher J. Baldwin, David J. Loury, Reyna J. Simon, Robert R. Webb
Abstract: Epothilone A, epothilone B, analogs of epothilone and libraries of epothilone analogs are synthesized. Epothilone A and B are known anticancers agents that derive their anticancer activity by the prevention of mitosis through the induction and stabilization of microtubulin assembly. The analogs of epothilone are novel. Several of the analogs are demonstrated to have a superior cytotoxic activity as compared to epothilone A or epothilone B as demonstrated by their enhanced ability to induce the polymerization and stabilization of microtubules.
Type:
Application
Filed:
December 9, 2003
Publication date:
July 1, 2004
Applicant:
The Scripps Research Institute
Inventors:
Kyriacos C. Nicolaou, Yun He, Sacha Ninkovic, Joaquin Pastor, Frank Roschangar, Francisco Sarabia, Hans Vallberg, Dionisios Vourloumis, Nicolas Winssinger, Zhen Yang, Nigel Paul King, M. Ray Finlay
Abstract: There are described novel 5-O-mycaminosyltylonide (OMT) analogs possessing increased antibacterial activity toward Gram positive and Gram negative bacteria as well as macrolide resistant Gram positives and pharmaceutically acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier.
Type:
Grant
Filed:
April 19, 2002
Date of Patent:
June 22, 2004
Assignee:
Enanta Pharmaceuticals, Inc.
Inventors:
Ly Tam Phan, Yao-Ling Qiu, Yat Sun Or, Nha Vo, Tianying Jian, Ying Hou, Marina Busuyek
Abstract: Derivatives of apoptolidin, including skeletal homologues, are potent and selective apoptosis-inducing agents which, unlike apoptolidin, do not undergo isomerization under physiological conditions. These compounds exhibit antitumor properties, often superior to those of apoptolidin, and as such can be used in the treatment of cancer and other hyperproliferative disorders.
Abstract: Macrolide compounds produced by culturing novel mutant Saccharopolyspora sp. strains have insecticidal and acaricidal activity and are useful intermediates for preparing spinosyn analogs.
Type:
Application
Filed:
September 15, 2003
Publication date:
May 20, 2004
Inventors:
Donald R. Hahn, Jesse L. Balcer, Paul Lewer, Jeffrey R. Gilbert, Paul R. Grausner
Abstract: The present invention provides an isolated polypeptide comprising a nucleotide sequence encoding a protein which is involved in midecamycin biosynthesis, wherein said protein comprises an amino acid sequence selected from SEQ ID NOs: 2 to 10, 13, 14, 16, 19, 20, 22 to 26, and 28 to 38 or a modified amino acid sequence of said amino acid sequence having one or more amino acid modifications without affecting activity of the protein.
Abstract: The present invention relates to 11,12 &ggr; lactone ketolides of formula (I) wherein R, R1, R2, R3 are as defined herein and pharmaceutically acceptable salts and solvates thereof, to process for their preparation and their use in therapy or prophylaxis of systemic or topical bacterial infections in a human or animal body.
Abstract: The present invention is to obtain novel anti-inflammatory agents having decreased antibacterial activity and increased anti-inflammatory action, and is psedoerythromycin derivatives represented by the following general formula [I], 1
Abstract: The present invention provides methods for purifying and using optically active isomers of erythromycin as well as compositions comprising such optically active isomers. Such optically active isomers having desired actions as an antibiotic substantially separable from undesirable effects on GI motility and the cardiac potassium channels such that the cardiac action potential is not prolonged and the QT interval on the surface EKG (electrocardiogram) is not increased, such that the erythromycin can be useful for more effective therapy of systemic infections. Also disclosed are methods for assaying the levels of such isomers present in the biological fluids.
Abstract: There are described novel 5-O-mycaminosyltylonide derivatives and pharmaceutically acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier. Also described are a method for treating bacterial infections by administering to an animal a pharmaceutical composition containing a therapeutically-effective amount of a compound of the invention, and processes for the preparation of such compounds.
Type:
Grant
Filed:
April 19, 2002
Date of Patent:
March 23, 2004
Assignee:
Enanta Pharmaceuticals, Inc.
Inventors:
Ly Tam Phan, Nha Vo, Yat Sun Or, Yao-Ling Qiu, Ying Hou
Abstract: Novel 11-12 substituted lactone ketolide derivatives and pharmaceutically-acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically-acceptable carrier are described. Also described are a method for treating bacterial infections by administering to an animal a pharmaceutical composition containing a therapeutically effective amount of a compound of the invention and processes for the preparation of such compounds.
Type:
Application
Filed:
August 19, 2002
Publication date:
February 26, 2004
Inventors:
Nha Huu Vo, Ly Tam Phan, Ying Hou, Tongzhu Liu, Yat Sun Or
Abstract: The present invention provides a new class of polyene macrolide derivatives useful for treating or preventing fungal infections. The new polyene macrolide derivatives exhibit surprisingly superior antifungal activity and water solubility compared to amphotericin B methyl ester (AME). In addition, the new polyene macrolide derivatives have improved water solubility and lower toxicity than both amphotericin B (AmB) and AME.
Type:
Application
Filed:
April 25, 2003
Publication date:
February 12, 2004
Applicant:
Micrologix Biotech Inc.
Inventors:
Christopher J. Baldwin, Conway Cheng Chang, Binh T. Dang
Abstract: Novel 6,11-4-carbon bridged ketolides, pharmaceutically-acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically-acceptable carrier are described. Also described are a method for treating bacterial infections by administering to an animal a pharmaceutical composition containing a therapeutically effective amount of a compound of the invention and processes for the preparation of such compounds.
Type:
Application
Filed:
July 25, 2002
Publication date:
February 5, 2004
Inventors:
Yat Sun Or, Guoqiang Wang, Deqiang Niu, Ly Tam Phan
Abstract: The present invention provides, inter alia, polyketide macrolides including a polyketide macrolide of the structure
wherein R1-R5 are the same or different and each is independently selected from the group consisting of hydrogen, R6, a C(O)R7, a C(S)R7, a C(O)NHR7, and a C(S)NHR7, each occurrence of R6 is independently selected from the group consisting of a C1-C6 alkyl, a C5-C12 aryl, and a sugar, each occurrence of R7 is independently selected from the group consisting of hydrogen, a C1-C6 alkyl, and a C5-C12 aryl, and wherein R1 and R2, R2 and R3, and/or R4 and R5 can be taken together to form a ketal ring. Also provided are asceptic mixtures of polyketide macrolides isolated from M.
Type:
Grant
Filed:
February 27, 2002
Date of Patent:
January 20, 2004
Assignee:
The United States of America as represented by the Department
of Health and Human Services
Abstract: There are described novel 4′ substituted 16-membered macrolides and pharmaceutically acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier. Also described are a method for treating bacterial infections by administering to a mammal a pharmaceutical composition containing a therapeutically-effective amount of a compound of the invention, and processes for the preparation of such compounds.
Type:
Grant
Filed:
July 27, 2001
Date of Patent:
January 20, 2004
Assignee:
Enanta Pharmaceuticals, Inc.
Inventors:
Yat Sun Or, Ly Tam Phan, Zhaolin Wang, Tianying Jian
Abstract: The present invention relates to a cost effective and industrially advantageous process for the selective methylation of a hydroxy group at the 6 position of erythromycin A derivatives.
Abstract: There are described novel substituted tylosin analogs and pharmaceutically acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier. Also described is a method for treating bacterial infections by administering to a mammal a pharmaceutical composition containing a therapeutically-effective amount of a compound of the invention, and processes for the preparation of such compounds.
Type:
Grant
Filed:
November 15, 2001
Date of Patent:
December 16, 2003
Assignee:
Enanta Pharmaceuticals, Inc.
Inventors:
Ly Tam Phan, Marina V. Busuyek, Yat Sun Or
Abstract: The invention provides single-dose oral formulations for controlling an ectoparasite infestation on a companion animal for a prolonged time, said formulations comprising a spinosyn component, or a physiologically acceptable derivative or salt thereof, and a carrier in oral dosage form. It also provides methods for controlling such infestations comprising orally administering a single dose of these formulations to the animal.
Abstract: The present invention provides two new classes of polyene macrolide amide derivatives useful for treating or preventing fungal infections. The new polyene macrolide amide derivatives exhibit antifungal activity and are more water-soluble than conventional polyene antibiotics, such as amphotericin B and amphotericin B methyl ester.
Type:
Grant
Filed:
May 29, 2001
Date of Patent:
December 16, 2003
Assignee:
Micrologix Biotech Inc.
Inventors:
Conway C. Chang, Binh T. Dang, Christopher J. Baldwin, David J. Loury, Reyna J. Simon, Robert R. Webb
Abstract: A compound represented by the following general formula (I) or a salt thereof:
wherein R&agr; represents a C1-C10 alkyl group, a C3-C10 alkenyl group, a C7-C15 aralkyl group, a quinolinylalkyl group, a quinolinylalkenyl group, a C2-C10 alkylcarbonyl group, a C7-C15 aralkylcarbonyl group, a C4-C7 cycloalkylcarbonyl group, benzoyl group, an imidazolylcarbonyl group and the like; R1 represents hydrogen atom, a C1-C10 alkyl group, or a C2-C10 alkylcarbonyl group; and R2 represents hydrogen atom, a C1-C10 alkyl group, or a C2-C10 alkylcarbonyl group, provided that the compound wherein R&agr; represents a C2-C10 alkylcarbonyl group and both of R1 and R2 represent a C1-C10 alkyl group is excluded.
Abstract: The invention provides, biologically active spinosyns, hybrid spinosyn polyketide synthases capable of functioning in Saccharopolyspora spinosa to produce the spinosyns, and methods of controlling insects using the spinosyns.
Type:
Application
Filed:
February 19, 2003
Publication date:
December 4, 2003
Inventors:
Lesley S. Burns, Paul R. Graupner, Paul Lewer, Christine J. Martin, William A. Vousden, Clive Waldron, Barrie Wilkinson
Abstract: The present invention relates to processes for converting clarithromycin Form I to clarithromycin Form II, which include slurrying clarithromycin the Form I in water. The present invention also relates to processes for the preparation of clarithromycin Form II by converting erythromycin A to clarithromycin and thereafter converting clarithromycin Form I to clarithromycin Form II by slurrying.
Type:
Application
Filed:
June 10, 2003
Publication date:
November 20, 2003
Inventors:
Igor Lifshitz, Ilya Avrutov, Edi Schwartz, Basem Masarwa
Abstract: The present invention provides compositions and methods which can provide a pesticidal effect. The compositions typically comprise 4-phenoxyphenyl 2-(2-pyridyloxy)propyl ether and an ether compound encompassed by formula I:
wherein R represents a methyl group or ethyl group.
The methods comprise applying a pesticidally effective amount of the composition to a pest of a habitat of a pest.
Abstract: A safe and effective process for the oxidation of a primary or secondary alcohol to the corresponding aldehyde or ketone via the reaction of said alcohol with an anhydride solution of a 1,1,1-tri(C2-C4 alkanoyloxy-1,1 -dihydro-1,2-benziodoxol-3(1H)-one, and a composition useful in this process.
Type:
Application
Filed:
April 3, 2003
Publication date:
October 30, 2003
Applicant:
Wyeth
Inventors:
Ugo Chiacchio, Antonio Rescifina, Giuseppe Miraglia, Mariangela Magnano, Paola Di Raimondo
Abstract: The invention provides new macrolides antibiotics of formula (I) with improved biological properties and improved stability formula (I): wherein R1 is hydrogen, cyano, —S(L)mR2, —S(O)(L)mR2, or —S(O)2(L)mR2; L represents —(CH2)n— or —(CH2)nZ(CH2)n′—-; m is 0 or 1; n is 1, 2, 3, or 4; n′ is 0, 1, 2, 3, or 4; Z is O, S or NH; R2 is hydrogen, alkyl, heterocyclyl or aryl; which heterocyclyl and the aryl groups may be further substituted; * indicates a chiral center which is in the (R) or (S) form and pharmaceutically acceptable acid addition salts or in vivo cleavable esters thereof.
Type:
Application
Filed:
February 21, 2003
Publication date:
October 23, 2003
Inventors:
Peter Angehrn, Daniel Hunziker, Pierre-Charles Wyss
Abstract: Combinatorial libraries of polyketides can be obtained by suitable manipulation of a host modular polyketide synthase gene cluster such as that which encodes the PKS for erythromycin. The combinatorial library is useful as a source of pharmaceutically active compounds. In addition, novel polyketides and antibiotics are prepared using this method.
Type:
Application
Filed:
January 10, 2003
Publication date:
October 16, 2003
Inventors:
Chaitan Khosla, Gary Ashley, Hong Fu, Camilla M. Kao, Robert McDaniel
Abstract: There is provided a preparation process useful for an efficient synthesis of 6-O-substituted ketolide derivatives by combining a characterized step of introduction of a substituent at the 6-position by selective cleavage of a C—O bond of the cyclic acetal at the 9-position side via 6,9-cyclic acetal 5-O-desosaminyl erythronolide derivative, a step of conversion into carbonyl groups at the 9- and 3-positions, and a step of 11,12-cyclic carbamation to lead to 6-O-substituted ketolide derivatives.
Abstract: The present invention provides an E-type crystal of N-demethyl-N-isopropyl-12-methoxy-11-oxo-8,9-anhydroerythromycin A-6,9-hemiacetal fumarate having strong diffraction peaks at diffraction angles (2&thgr;) of 5.6° and 10.4° as measured by powder X-ray diffractometry, which is prepared by treating a C-type crystal of the compound in a mixed solvent of ethyl acetate and water at 20° C. to 40° C., and a D-type crystal prepared via the E-type crystal. These crystals have a reduced content of residual solvent and high suitability for formulation.
Abstract: Macrolide compounds produced by culturing Saccharopolyspora species LW107129 (NRRL 30141) have insecticidal and acaricidal activity and are useful intermediates for preparing spinosyn analogs.
Type:
Application
Filed:
August 13, 2002
Publication date:
October 2, 2003
Inventors:
Paul Lewer, Donald R. Hahn, Laura L. Karr, Paul R. Graupner, Jeffrey R. Gilbert, Thomas V. Worden, Raymond C. Yao, Dennis W. Norton
Abstract: 6-O-Carbamoyl ketolide antibacterials of the formula:
wherein R1, R2, R3, R4, R5, R6, X, X′, Y, and Y′ are as described herein and in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.