- THERAPEUTIC COMPOSITIONS CONTAINING GLUTATHIONE ANALOGS
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Pharmaceutical compositions and methods of using them. Lipid formulations of a glutathione analog and methods of manufacturing them. Their use to stimulate hematopoiesis, protect hematopoietic cells from damage caused by radiation or chemotherapy, or potentiate the stimulatory action of one or a combination of cytokines on colony formation by hematopoietic progenitor cells, protect a subject from a destructive effect of a chemotherapeutic agent or irradiation, or to potentiate the effect of a chemotherapeutic agent.
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- Methods for isolating nucleic acids from biological and cellular materials
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Methods of isolating nucleic acids from samples of biological or cellular material are disclosed which use solid phase binding materials and which avoid the use of any lysis solution or coating. The use of the solid phase binding materials unexpectedly allow the nucleic acid content of cells to be freed and captured directly and in one step. The new methods represent a significant simplification over existing methods. Nucleic acids can be captured and released in a form suitable for downstream processing in under five minutes. Preferred solid phase materials for use with the methods and compositions of the invention comprise a quaternary onium nucleic acid binding portion.
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- 5,6,7-trinor-4,8-inter-m-phenylene PGI2, derivative and drugs containing the same
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The present invention provides novel PGI2derivatives and an anti Helicobacter agent, a platelet function potentiating agent or a cervical ripening agent containing any of the derivatives.
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- Substituted gamma-phenyl-delta-lactams and uses related thereto
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gamma-Phenyl-substituted Delta-lactams are disclosed. They may be formulated into pharmaceutical compositions, and/or used in the treatment or prevention of inflammation or other conditions or disease states.
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- Modulators of LXR
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Compounds, compositions and methods for modulating the activity of nuclear receptors are provided. In particular, heterocyclic compounds are provided for modulating the activity of nuclear receptors, including liver X receptor (LXR) and orphan nuclear receptors. In certain embodiments, the compounds are N-substituted pyridones.
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- Therapeutic compositions containing glutathione analogs
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Pharmaceutical compositions and methods of using them. Lipid formulations of a glutathione analog and methods of manufacturing them. Their use to stimulate hematopoiesis, protect hematopoietic cells from damage caused by radiation or chemotherapy, or potentiate the stimulatory action of one or a combination of cytokines on colony formation by hematopoietic progenitor cells, protect a subject from a destructive effect of a chemotherapeutic agent or irradiation, or to potentiate the effect of a chemotherapeutic agent.
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- 3-nitrogen-6,7-dioxygen steroids and uses related thereto
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A compound of the formula and pharmaceutically acceptable salts, solvates, stereoisomers and prodrugs thereof, in isolation or in mixture, wherein, independently at each occurrence: R1 and R2 are selected from hydrogen, oxygen so as to form nitro or oxime, amino, sulfate, and sulfonic acid, and organic groups having 1-30 carbons and optionally containing 1-6 heteroatoms selected from nitrogen, oxygen, phosphorous, silicon, and sulfur, where R1 and R2 may, together with the N to which they are both bonded, form a heterocyclic structure that may be part of an organic group having 1-30 carbons and optionally containing 1-6 heteroatoms selected from nitrogen, oxygen and silicon, and where R1 may be a 2, or 3 atom chain to numeral 2 so that —N—R1— forms part of a fused bicyclic structure to ring A; R3 and R4 are selected from direct bonds to 6 and 7 respectively so as to form carbonyl groups, hydrogen, or a protecting group such that R3 and/or R4 is part of hydroxyl or carbonyl protecting group; numerals 1 through 17 each represent a carbon having substitution as described. The compounds may be formulated into pharmaceutical compositions, and used in the treatment and/or prevention of various conditions, including inflammation, asthma, an allergic disease, chronic obstructive pulmonary disease, atopic dermatitis, solid tumors, AIDS, ischemia, and cardiac arrhythmias.
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- Method for lowering blood alcohol concentration by administering an extract of Rhus verniciflua
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A method for lowering blood alcohol concentration by administering an extract ofRhus vernicifluato human, thereby preventing or treating a disease state caused by intake of an alcohol.
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- Synthesis of low-fluoride organic compounds
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Organic compounds, e.g. fluorinated organic compounds such as fluorinated carboxylic acids or fluorinated carboxylic acid chlorides, may contain small amounts of carboxylic acid fluorides, hydrogen fluoride or hydrolyzable fluoride, which during the preparation of derivatives of the fluorinated organic compounds, for example by esterification, may yield corrosive fluorides or hydrogen fluoride. The invention is a method for the synthesis and/or purification of preferably fluorinated organic compounds such as carboxylic acids, carboxylic acid chlorides and derivatives such as esters thereof, starting from corresponding carboxylic acid chlorides containing acid fluorides or hydrolyzable fluoride, and alcohols under the catalytic action of “onium” salts of carboxylic acids, to obtain products which have a low fluoride content. Alternatively, an inorganic oxide adsorbent is utilized. The method is especially suitable for the synthesis of esters of trifluoroacetic acid, chlorodifluoroacetic acid, trifluoroacetoacetic acid and/or difluoroacetoacetic acid.
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- Nocathiacin antibiotics
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Novel thiazolyl peptide antibiotic compounds, including nocathiacin I, II and III, are disclosed. Also, novel microorganism ATCC-202099 is disclosed.
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- Manipulating nucleic acid sequences
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A method of effecting a manipulation of a nucleic acid sequence comprises (a) providing a solid support system having bonded thereto a single stranded oligonucleotide complementary to a specific sequence on a target nucleic acid longer than said oligonucleotide, (b) adding a source of single stranded target nucleic acid to the solid support system, (c) hybridising the target nucleic acid to the oligonucleotide, and (d) effecting the manipulation on the hybridised target nucleic acid. The manipulation may for example be a copying or amplification of the target nucleic acid sequence. In a preferred embodiment, the support is provided in a flow-through vessel which facilitates washing of the support to remove impurities and leave a "clean" sample of target nucleic acid on which the manipulation may be carried out. The support preferably has a siloxane matrix to which the oligonucleotide is bound. This provides a stable linkage between the oligonucleotide and the support. The method is particularly useful for analysis of medical samples.
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- AROMATIC HETEROCYCLIC DERIVATIVES AS ENZYME INHIBITORS
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The present invention discloses peptide aldehydes which are potent and specific inhibitors of thrombin, their pharmaceutically acceptable salts, pharmaceutically acceptable compositions thereof, and methods of using them as therapeutic agents for disease states in mammals characterized by abnormal thrombosis.
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- Texaphyrin solid supports and devices
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The present invention provides various novel matrix-supported texaphyrins in which a polymeric or solid matrix is covalently modified by the addition of one or more texaphyrins or texaphyrin derivatives. Described are methods of making various polymer-supported texaphyrins, including texaphyrin chromatographic supports, and devices such as catheters, as may be used, for example, in the separation of neutral and anionic species and in applications concerning phosphate ester hydrolysis, other catalytic schemes, MRI, and PDT.
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- Process for preparing low unsaturation polyether polyols
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Polyether polyols having reduced terminal unsaturation are prepared in a process comprising a first step of contacting a polyether having allyl terminal unsaturation with an isomerization catalyst whereby the allyl terminal unsaturation of the polyether is reduced by at least 90% conversion to propenyl terminal unsaturation in one step and, in a final step, the resulting polyether product of the first step is contacted with an acid catalyst whereby a substantial amount of the propenyl terminal unsaturation of the polyether is removed and the corresponding polyether having an additional hydroxyl group is obtained.
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- Solid support reagents for the synthesis of 3'-Nitrogen containing polynucleotides
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The compounds are exemplified by the class of sulfoethyl oxygen-substituted carbamates, such compounds being useful as support reagents for automated polynucleotide synthesis of 3'-nitrogen functionalized polynucleotides. The invention includes, in one as
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- Dideoxyfructonucleosides and deoxyfructonucleotides
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Disclosed are deoxyfructonucleotides and dideoxyfructonucleotides which may be used as propagators and terminators in DNA extension reactions.
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- Compositions and methods for drug delivery and chromatography
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Cyclodextrin derivatives and inclusion complexes having increased solubility and stability are provided. Cyclodextrin derivatives include amino and other modified cyclodextrins, and linked cyclodextrins. Inclusion complexes comprising the foregoing cyclod
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- Phosphorylation with monomeric metaphosphates
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Solid substrates with free hydroxyl groups are phosphorylated by thermolysing a solution of phosphoramidate of the formula STR1 in the presence of the substrate, whereby metaphosphate is generated which phosphorylates the substrate.
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- ddI immunoassays, derivatives, conjugates and antibodies
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This invention relates to a method for the immunoassay of ddI (2',3'-dideoxyinosine), also known as didanosine, in biological fluids such as serum, semen, plasma and urine, as well as other body fluids. The invention also includes (1) various novel analogs of ddI useful in preparing immunogens for antibodies to ddI and in preparing labeled ddI, (2) immunogens for antibodies to ddI, (3) antibodies to ddI, (4) labeled ddI analogs and (5) diagnostic test kits for the immunoassay.
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- Use of esters of acyl L-carnitines with gamma-hydroxybutyric acid for producing pharmaceutical compositions for the treatment of hepatopathies
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Esters of acyl L-carnitine with gamma-hydroxybutyric acid, both as pharmacologically acceptable salts of formula (1) STR1 and as inner salts of formula (1') STR2 wherein X- is the anion of a pharmacologically acceptable acid and R is a straight or branched acyl group having from 2 to 5 carbon atoms, are used for producing pharmaceutical compositions effective for treating hepatopathies.
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- Transesterification catalyst
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A process is described for preparing carboxylic acid esters via transestierification using a new heterogeneous, transition-metal transesterification catalyst of enhanced activity. The catalyst is prepared by an improved method of reacting a metal alkoxide to form an active species and absorbing the metal containing species onto a support. The method requires the controlled hydrolysis of a transition metal alkoxide to prepare an oligomer, which is then absorbed onto a hydroxylic support.
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- Process for purifying nucleic acids
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The process for separating the proteinaceous materials from nucleic acids involves contacting a solution containing the proteinaceous materials and nucleic acids with a solid phase extraction material capable of binding proteins to form bound and unbound fractions and then isolating the unbound fraction containing the nucleic acids.
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- Irreversible dopamine-β-hydroxylase inhibitors
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Potent, irreversible dopamine-β-hydroxylase inhibitors having the Formula: STR1 which are useful to inhibit dopamine-β-hydroxylase activity, pharmaceutical compositions including these inhibitors or 2-cyano-2-phenethylamine, and methods of using these inhibitors or 2-cyano-2-phenethylamine to inhibit dopamine-β-hydroxylase activity in mammals. Also disclosed are novel intermediates useful in preparing the presently invented inhibitors.
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- INTERMEDIATES FOR UREA AND THIOUREA DERIVATIVES
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This invention relates to amine derivatives and salts thereof. These compounds have an anti-ulcer activity which is effective to human beings and animals. This disclosure relates to such compounds, a process for the preparation thereof and an anti-ulcer agent containing the same.
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- Antibiotic 7-(thiazolyl)-3-(pyrazinylmethyl) or (pyridazinylmethyl) cephalosporins
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The invention relates to antibiotic compounds of the formula: STR1 wherein R1 represents a hydrogen atom or a carboxyl-protecting group; R2 represents a group of the formula: STR2 R3 represents a hydrogen atom or an alkoxy
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- Antibiotic 273a1
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Novel and useful antibiotics designated 273a1α; and 273a1β; can be produced in a fermentation using Streptomyces paulus, strain 273, NRRL 12251. These antibiotics are active against various Gram-positive bacteria. Also, these antibiotics are, advantageously, soluble in aqueous solutions.
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- 3-Substituted-6-(1'-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]-hept-2-ene-2-carboxylic acid
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Disclosed are 3-substituted-6-(1'-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acids having the structure: STR1 wherein R8 is, inter alia, selected from the group consisting of hydrogen, alkyl, alkenyl, aryl and aralkyl. Such
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- 3-Substituted-6-substituted-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
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Disclosed are 3- and 6-substituted 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acids having the structure: STR1 wherein R6, R7 and R8 are, inter alia, independently selected from the group consisting of hydrogen, alky
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- Derivatives of A-30912A nucleus
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Compounds of the formula STR1 wherein R1 is C6 -C24 alkyl or C6 -C24 alkenyl, have antifungal activity.
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- Derivatives of A-30912D nucleus
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Compounds of the formula STR1 wherein R1 is C6 -C24 alkyl or C6 -C24 alkenyl, have antifungal activity.
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- Derivatives of A-30912B nucleus
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Compounds of the formula STR1 wherein R1 is C6 -C24 alkyl or C6 -C24 alkenyl, have antifungal activity.
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- Derivatives of A-30912H nucleus
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Compounds of the formula STR1 wherein R1 is C6 -C24 alkyl or C6 -C24 alkenyl and R2 is C1 -C6 alkyl, have antifungal activity.
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- 2-, 5-, and 6-Substituted-1-carbadethiapen-2-em-3-carboxylic acids
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Disclosed are 2-, 5- and 6-substituted-1-carbadethiapen-2-em-3-carboxylic acids having the structure: STR1 wherein R6, R7, R8 and R9 are, inter alia, independently selected from the group consisting of hydrogen,
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- 5-Substituted-3-(2-aminoethylthio)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
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Antibiotic 5-substituted-3-(2-aminoethylthio)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acids (I) are disclosed: STR1 wherein R is alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl or heteroaryl.
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- 3-Trehalosamine compounds
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Novel antibiotic 3-trehalosamine (U-59,834) producible in a fermentation under controlled conditions using the new microorganism Nocardiopsis trehalosei sp. nov., NRRL 12026. This antibiotic is active against Gram-positive bacteria, for example, Staphylococcus aureus, Bacillus subtilis, and Diplococcus pneumoniae. Thus, 3-trehalosamine can be used in various environments to eradicate or control such bacteria. Antibiotic 3-trehalosamine can be shown by the following structural formula: STR1
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- Derivatives of A-30912D nucleus
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Compounds of the formula STR1 wherein R1 is a group of the formula: STR2 wherein A is divalent oxygen, sulfur, sulfinyl, or sulfonyl; A1 is divalent oxygen, sulfur, sulfinyl, sulfonyl or --NH--; X is hydrogen, chloro, bromo, iodo, nitro, C1 -C3 alkyl, hydroxy, C1 -C3 alkoxy, mercapto, C1 -C3 alkylthio, carbamyl or C1 -C3 alkylcarbamyl; X1 is chloro, bromo or iodo; R2 is hydrogen, C1 -C18 alkyl or C2 -C18 alkenyl; W is C1 -C10 alkylene or C2 -C10 alkenylene; m, n and p are 0 or 1, but if m=0, n must=0; provided: that the sum of the carbon atoms in the R2 and W groups must be greater than 4 but cannot exceed 21; that when X is mercapto, A and A1 cannot be sulfinyl or sulfonyl; and that when A and A1 are sulfinyl or sulfonyl, they must be in equal oxidation states.
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- Derivatives of A-30912B nucleus
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Compounds of the formula STR1 wherein R1 is a group of the formula: STR2 wherein A is divalent oxygen, sulfur, sulfinyl, or sulfonyl; A1 is divalent oxygen, sulfur, sulfinyl, sulfonyl or --NH--; X is hydrogen, chloro, bromo, iodo, nitro, C1 -C3 alkyl, hydroxy, C1 -C3 alkoxy, mercapto, C1 -C3 alkylthio, carbamyl or C1 -C3 alkylcarbamyl; X1 is chloro, bromo or iodo; R2 is hydrogen, C1 -C18 alkyl or C2 -C18 alkenyl; W is C1 -C10 alkylene or C2 -C10 alkenylene; m, n and p are 0 or 1, but if m=0, n must=0; provided: that the sum of the carbon atoms in the R2 and W groups must be greater than 4 but cannot exceed 21; that when X is mercapto, A and A1 cannot be sulfinyl or sulfonyl; and that when A and A1 are sulfinyl or sulfonyl, they must be in equal oxidation states.
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- Derivatives of A-30912H nucleus
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Compounds of the formula STR1 wherein R3 is C1 -C6 alkyl and R1 is a group of the formula: STR2 wherein A is divalent oxygen, sulfur, sulfinyl, or sulfonyl; A1 is divalent oxygen, sulfur, sulfinyl, sulfonyl or --NH--; X is hydrogen, chloro, bromo, iodo, nitro, C1 -C3 alkyl, hydroxy, C1 -C3 alkoxy, mercapto, C1 -C3 alkylthio, carbamyl or C1 -C3 alkylcarbamyl; X1 is chloro, bromo or iodo; R2 is hydrogen, C1 -C18 alkyl or C2 -C18 alkenyl; W is C1 -C10 alkylene or C2 -C10 alkenylene; m, n and p are 0 or 1, but if m=0, n must =0; provided: that the sum of the carbon atoms in the R2 and W groups must be greater than 4 but cannot exceed 21; that when X is mercapto, A and A1 cannot be sulfinyl or sulfonyl; and that when A and A1 are sulfinyl or sulfonyl, they must be in equal oxidation states.
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- Derivatives of A-30912A nucleus
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Compounds of the formula STR1 wherein R1 is a group of the formula: STR2 wherein A is divalent oxygen, sulfur, sulfinyl, or sulfonyl; A1 is divalent oxygen, sulfur, sulfinyl, sulfonyl or --NH--; X is hydrogen, chloro, bromo, iodo, nitro, C1 --C3 alkyl, hydroxy, C1 -C3 alkoxy, mercapto, C1 -C3 alkylthio, carbamyl or C1 -C3 alkylcarbamyl; X1 is chloro, bromo or iodo; R2 is hydrogen, C1 -C18 alkyl or C2 -C18 alkenyl; W is C1 -C10 alkylene or C2 -C10 alkenylene; m, n and p are 0 or 1, but if m=0, n must=0; provided: that the sum of the carbon atoms in the R2 and W groups must be greater than 4 but cannot exceed 21; that when X is mercapto. A and A1 cannot be sulfinyl or sulfonyl; and that when A and A1 are sulfinyl or sulfonyl, they must be in equal oxidation states.
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- A-30912H Nuclei
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A-30912H-type nuclei of formula 1, which are prepared by enzymatic deacylation of an antibiotic having formula 2 using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. A-30912H-type nuclei and salts thereof are useful inter
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- S 31794/F-1 Nucleus
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S 31794/F-1 nucleus, which is prepared by enzymatic deacylation of antibiotic S 31794/F-1 using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. S 31794/F-1 nucleus and salts thereof are useful intermediates for the prepara
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- Derivatives of S31794/F-1 nucleus
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Compounds of the formula STR1 wherein R1 is C6 -C24 alkyl or C6 -C24 alkenyl, have antifungal activity.
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- Derivatives of S31794/F-1 nucleus
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Compounds of the formula STR1 wherein R1 is an N-alkanoyl amino acyl group of the formula STR2 wherein: W is a divalent aminoacyl radical of the formula: STR3 wherein A is C1 -C10 alkylene or C5 -C6 c
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- A-30912D Nucleus
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A-30912D nucleus, which is prepared by enzymatic deacylation of an antibiotic selected from A-30912 factor D and tetrahydro-A-30912D using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. A-30912D nucleus and salts thereof
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- A-30912B Nucleus
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A-30912B nucleus, which is prepared by enzymatic deacylation of an antibiotic selected from A-30912 factor B and tetrahydro-A-30912B using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. A-30912B nucleus and salts thereof
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- A-30912A Nucleus
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A-30912A nucleus, which is prepared by enzymatic deacylation of an antibiotic selected from A-30912 factor A, tetrahydro-A-30912A, and aculeacin A using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. A-30912A nucleus and
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- Derivatives of A-30912B nucleus
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Compounds of the formula STR1 wherein R1 is an N-alkanoyl amino acyl group of the formula STR2 wherein: W is a divalent aminoacyl radical of the formula: STR3 wherein A is C1 -C10 alkylene or C5 -C6 c
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- Derivatives of S31794/F-1 nucleus
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Compounds of the formula STR1 wherein R1 is a group of the formula: STR2 wherein A is divalent oxygen, sulfur, sulfinyl, or sulfonyl; A1 is divalent oxygen, sulfur, sulfinyl, sulfonyl or --NH--; X is hydrogen, chloro, bromo, iodo, nitro, C1 -C3 alkyl, hydroxy, C1 -C3 alkoxy, mercapto, C1 -C3 alkylthio, carbamyl or C1 -C3 alkylcarbamyl; X1 is chloro, bromo, or iodo; R2 is hydrogen, C1 -C18 alkyl or C2 -C18 alkenyl; W is C1 -C10 alkylene or C2 -C10 alkenylene; m, n and p are 0 or 1, but if m=0, n must=0; provided: that the sum of the carbon atom in the R2 and W groups must be greater than 4 but cannot exceed 21; that when X is mercapto, A and A1 cannot be sulfinyl or sulfonyl; and that when A and A1 are sulfinyl or sulfonyl, they must be in equal oxidation states.
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