Patents Assigned to Boron Biologicals, Inc.
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Patent number: 5659027Abstract: A novel class of pharmaceutically active boronated compounds are provided. The boronated compounds include boronated purine and pyrimidine bases and boronated nucleosides, as well as phosphate esters and oligomers thereof. The compounds are boronated at the ring nitrogen of the purine or pyrimidine base, or at a 2', 3' or 5' amino substituent of the nucleoside sugar.Type: GrantFiled: November 4, 1994Date of Patent: August 19, 1997Assignees: University of North Carolina, Boron Biologicals, Inc., Duke UniversityInventors: Bernard F. Spielvogel, Anup Sood, Iris H. Hall, Barbara Ramsay Shaw, Jeno Tomasz
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Patent number: 5595878Abstract: A method is disclosed for detecting boron labeled biopolymers, biooligomers, and other species that bind to the biopolymers, and biooligomers with specificity. The biopolymers include RNA, DNA and proteins. The biooligomers include RNA oligomers, DNA oligomers, and peptides. The biopolymers and biooligomers are labeled with a borane, or a boron-hydride moiety. The borane and boron-hydride moiety are employed to reduce a metal ion, e.g. silver, to metal or metal oxide, metal boride or other metal species, or alternatively to reduce a dye, or another organic or inorganic compound. The product of the reduction reaction can be visualized with or without signal augmentation, by one or more means, including the naked eye or a microscope, or can be detected through the use of analytical equipment that can detect conductivity, voltage, density, ultraviolet or visible light, fluorescence, luminescence, phosphorescence, paramagnetism, magnetic susceptibility, or any other detectable physical property.Type: GrantFiled: June 2, 1995Date of Patent: January 21, 1997Assignee: Boron Biologicals, Inc.Inventors: Anup Sood, Bernard F. Spielvogel
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Patent number: 5545397Abstract: Contrast agent for X-ray imaging, consisting of a halogenated, especially iodinated or brominated, derivative of boron, having characteristics necessary for its use in X-ray imaging. The contrast agent may be used for imaging a corporeal situs by radiological techniques, comprising delivery to the corporeal situs of an imagingly effectively amount of a physiologically acceptable composition comprising the boron reagent. A variety of illustrative boron reagents is described, including vectorised boron derivatives, e.g., boron derivatives encapsulated within liposomes, fixed on or bonded to macromolecules or polymers, etc. The contrast agents, formulations, and method of the present invention may be employed for a wide variety of radiological imaging applications, e.g., excretory urography, angiocardiography, aortography, etc.Type: GrantFiled: November 18, 1994Date of Patent: August 13, 1996Assignees: Boron Biologicals, Inc., Guerbet S.A.Inventors: Bernard F. Spielvogel, Dominique Meyer
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Patent number: 5455233Abstract: Disclosed are oligonucleoside boranophosphates, or salts thereof, comprising a chain of natural or modified ribonucleotides or deoxyribonucleotides, containing at least one boronated internucleotide phospodiester linkage of the formula: ##STR1## W is selected from the group consisting of .dbd.O, .dbd.S, --OPr, and --SPr where Pr is a base-labile protecting group. X is selected from the group consisting of --BH.sub.3, --BH.sub.2 R.sub.1, --BHR.sub.1 R.sub.2 and --BR.sub.1 R.sub.2 R.sub.3. R.sub.1 is selected from the group consisting of --R.sub.4, --COOH, --COOR.sub.4, --CONHR.sub.4, --CON(R.sub.4).sub.2, --CN.sup.+ R.sub.4 Z.sup.-, wherein Z.sup.- is an anion, --CN, carboxycholesteryl and carboxybenzyl, wherein R.sub.4 is C1 to C18 alkyl. R.sub.2 is selected from the group consisting of --R.sub.5, --COOH, --COOR.sub.5, --CONHR.sub.5, --CON(R.sub.5).sub.2, --CN.sup.+ R.sub.5 Z.sup.-, wherein Z.sup.- is an anion, --CN, carboxy- cholesteryl and carboxybenzyl, wherein R.sub.5 is C1 to C18 alkyl. R.sub.Type: GrantFiled: September 30, 1992Date of Patent: October 3, 1995Assignees: University of North Carolina, Duke University, Boron Biologicals, Inc.Inventors: Bernard F. Spielvogel, Anup Sood, Iris H. Hall, Barbara R. Shaw
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Patent number: 5434143Abstract: The phosphite-borane compounds of the present invention correspond to the formula ##STR1## where R.sub.1 is independently selected from H, C.sub.1 -C.sub.20 alkyl, alkylaryl, aryl, trialkylsilyl, with the proviso that both R.sub.1 groups cannot simultaneously be H.sub.1, andR.sub.2 is selected from H, a monovalent cation such as Li.sup.+, Na.sup.+, K.sup.+, NH.sub.4.sup.+, N(R.sub.3.sup.+).sub.4, where R.sub.3 is independently selected from H, C.sub.1 -C.sub.20 alkyl.The phosphite-borane compounds of the present invention are bioactive in character, variously exhibiting anti-tumor, anti-inflammatory, and hypolipidemic activity. Also disclosed are various synthetic methods for making such phosphite-borane compounds, and for formulating same in unit dosage forms as well as other pharmaceutically and pharmacologically acceptable formulations.Type: GrantFiled: October 19, 1994Date of Patent: July 18, 1995Assignee: Boron Biologicals, Inc.Inventors: Bernard F. Spielvogel, Anup Sood
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Patent number: 5399732Abstract: Methods of making phosphite-borane compounds of the formula ##STR1## wherein: each R.sub.1 is independently selected from: H; C.sub.1 -C.sub.10 alkyl; alkylaryl; aralkyl; aryl; monovalent metal ions; nucleosides; and quaternary ammonium ions, (R.sub.4).sub.4 N.sup.+, in which the substituents R.sub.4 of the ammonium nitrogen atom are H or C.sub.1 -C.sub.10 alkyl;R.sub.2 is H or C.sub.1 -C.sub.10 alkyl; andR.sub.3 is CNCH.sub.2 CH.sub.3.sup.+ BF.sub.4.sup.-, COOH, carboxyl salts, COOR.sub.5, or CONHR.sub.5, wherein R.sub.5 is C.sub.1 -C.sub.10 alkyl, alkylaryl, aralkyl, or aryl;with the proviso that if at least one of the R.sub.1 substituents is H, nucleoside, monovalent metal ion, or quaternary ammonium ion, then R.sub.3 may also be CN,via synthetic routes comprising hydrolysis. The phosphorous-boron adducts of the invention are bioactive in character, variously exhibiting anti-tumor, anti-inflammatory, and hypolipidemic activity.Type: GrantFiled: October 14, 1993Date of Patent: March 21, 1995Assignee: Boron Biologicals Inc.Inventors: Bernard F. Spielvogel, Anup Sood
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Patent number: 5312816Abstract: A method of combatting, e.g., preventing as well as treating, a disease state such as cystic fibrosis, neonatal hypoxemia, pulmonary hypertension, adult respiratory distress syndrome, psoriasis, spondyloarthritis, rheumatoid arthritis, gout, inflammatory bowel disease, myocardial infarctions, and/or osteoporosis in an animal subject, by administering to the animal subject an amount of an organic boron compound which is effective thereagainst. The organic boron compounds usefully employed in the method of the invention include any suitable organic boron-containing compounds, such as Lewis base-boron adducts; a preferred class of organic boron compounds useful in such method includes boron analogs of .alpha.-amino acids, and the corresponding amides and esters of such amino acids. A method is also disclosed of inhibiting enzyme activity in in vitro or in vivo systems comprising administering to such system an enzyme-inhibiting amount of an organic boron compound.Type: GrantFiled: September 14, 1993Date of Patent: May 17, 1994Assignee: Boron Biologicals, Inc.Inventors: Bernard F. Spielvogel, Anup Sood, Iris H. Hall
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Boron-gadolinium compounds and method of conducting imaging and/or neutron capture therapy with same
Patent number: 5286853Abstract: A gadolinium (3.sup.+) complex of polyamine polyacetate, comprising a polyamine nucleus having a pendant boron-containing substituent on one of the nitrogen or carbon atoms of the polyamine nucleus. The boron-gadolinium compound may suitably be of the formula: ##STR1## wherein: is a polyamine coordination structure capable of covalently bonding the substitutents R.sub.1, R.sub.2, R.sub.3 and R.sub.4 and of complexing with Gd;R.sub.1, R.sub.2, and R.sub.3 are independently selected from carboxyl, carboxylic salt groups, carboxylic ester groups, and carboxylate anion;R.sub.4 is a boron-containing group; andx is a number from zero to 4.Type: GrantFiled: September 11, 1992Date of Patent: February 15, 1994Assignee: Boron Biologicals, Inc.Inventors: Bernard F. Spielvogel, Anup Sood -
Patent number: 5280119Abstract: Heterocyclic amine-borane compounds of the formula: ##STR1## wherein: A is a heterocyclic amine moiety selected from the group consisting of piperidine, substituted piperidine, piperazine, substituted piperazine, imidazole, substituted imidazole, pyrazole, substituted pyrazole, pyrazine, substituted pyrazine, pyrrole, substituted pyrrole, pyrrolidine, substituted pyrrolidine, indole, substituted indole, indoline, substituted indoline, quinoline, substituted quinoline, isoquinoline, substituted isoquinoline, thiazole, substituted thiazole, oxazole, substituted oxazole, thiazolidine, and substituted thiazolidine, wherein substitution is at any or all substituent positions, and comprises substituents selected from the group consisting of alkyl (preferably C.sub.1 -C.sub.10 linear or branched alkyl), alkylaryl, aryl, aralkyl, nitro, alkoxy, hydroxy, cyano, thiol, and halo;R.sub.1 is selected from H, alkyl (preferably C.sub.1 -C.sub.10 linear or branched alkyl), alkylaryl, aryl, and arylalkyl; andR.sub.Type: GrantFiled: November 1, 1991Date of Patent: January 18, 1994Assignee: Boron Biologicals, Inc.Inventors: Bernard F. Spielvogel, Anup Sood, Iris H. Hall
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Patent number: 5256394Abstract: A method of imaging a corporeal situs by radiological techniques, comprising delivery to the corporeal situs of an imagingly effectively amount of a physiologically acceptable composition comprising a boron reagent. A variety of illustrative boron reagents is described, including iodinated boron salts, and boron-containing cyclophosphazene and polyphosphazene reagents having radiopaque character. The reagents and method of the present invention may be employed for a wide variety of radiological imaging applications, e.g., excretory urography, angiocardiography, and aortography.Type: GrantFiled: October 23, 1991Date of Patent: October 26, 1993Assignee: Boron Biologicals, Inc.Inventor: Bernard F. Spielvogel
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Patent number: 5254706Abstract: Phosphite-borane compounds of the formula ##STR1## wherein: each R.sub.1 is independently selected from: H; C.sub.1 -C.sub.10 alkyl; alkylaryl; aralkyl; aryl; monovalent metal ions; nucleosides; and quaternary ammonium ions, (R.sub.4).sub.4 N.sup.+, in which the substituents R.sub.4 of the ammonium nitrogen atom are H or C.sub.1 -C.sub.10 alkyl;R.sub.2 is H or C.sub.1 -C.sub.10 alkyl; andR.sub.3 is CNCH.sub.2 CH.sub.3 .sup.+ BF.sub.4.sup.-, COOH, carboxyl salts, COOR.sub.5, or CONHR.sub.5, wherein R.sub.5 is C.sub.1 -C.sub.10 alkyl, alkylaryl, aralkyl, or aryl;with the proviso that if at least one of the R.sub.1 substituents is H, nucleoside, monovalent metal ion, or quaternary ammonium ion, then R.sub.3 may also be CN.The phosphorous-boron adducts of the invention are bioactive in character, variously exhibiting anti-tumor, anti-inflammatory, and hypolipidemic activity.Type: GrantFiled: August 31, 1992Date of Patent: October 19, 1993Assignee: Boron Biologicals, Inc.Inventors: Bernard F. Spielvogel, Anup Sood
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Patent number: 5177198Abstract: A process of making oligoribonucleoside and deoxyribonucleoside boranophosphates and salts thereof is disclosed. The process comprises the steps of condensing a ribonucleotide or deoxyribonucleotide with a nucleoside phosphitylating agent, wherein the phosphitylating agent includes a 5' -OH group protected by an acid-labile protecting group and a moiety bonded to the phosphorus atom therein that is a stronger proton acceptor than the 5'-OH group of the ribonucleotide or deoxyribonucleotide to form a reaction intermediate, then oxidizing the reaction intermediate so formed with a compound comprising a Lewis base and a boron-containing substituent, wherein the Lewis base is a weaker electron donor than the phosphite phosphorus of the reaction intermediate, to form a ribonucleotide or deoxyribonucleotide boranophosphate. These steps are repeated on the nucleotide boranophosphate to form an oligonucleotide boranophosphate.Type: GrantFiled: November 30, 1989Date of Patent: January 5, 1993Assignees: University of N.C. at Chapel Hill, Duke University, Boron Biologicals, Inc.Inventors: Bernard F. Spielvogel, Anup Sood, Iris H. Hall, Barbara Ramsay Shaw
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Patent number: 5143907Abstract: Phosphite-borane compounds of the formula ##STR1## wherein: each R.sub.1 is independently selected from: H; C.sub.1 -C.sub.10 alkyl; alkylaryl; aralkyl; aryl; monovalent metal ions; nucleosides; and quaternary ammonium ions, (R.sub.4).sub.4 N.sup.+, in which the substituents R.sub.4 of the ammonium nitrogen atom are H or C.sub.1 -C.sub.10 alkyl;R.sub.2 is H or C.sub.1 -C.sub.10 alkyl; andR.sub.3 is CNCH.sub.2 CH.sub.3.sup.+ BF.sub.4.sup.-, COOH, carboxyl salts, COOR.sub.5, or CONHR.sub.5, wherein R.sub.5 is C.sub.1 -C.sub.10 alkyl, alkylaryl, aralkyl, or aryl;with the proviso that if at least one of the R.sub.1 substituents is H, nucleoside, monovalent metal ion, or quaternary ammonium ion, then R.sub.3 may also be CN. The phosphorous-boron adducts of the invention are bioactive in character, variously exhibiting anti-tumor, anti-inflammatory, and hypolipidemic activity.Type: GrantFiled: May 10, 1991Date of Patent: September 1, 1992Assignee: Boron Biologicals, Inc.Inventors: Bernard F. Spielvogel, Anup Sood, Iris H. Hall
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Patent number: 5023513Abstract: Novel amine-alkylborane derivatives are disclosed which exhibit significant antineoplastic and antihyperlipidemic activities. Methods for preparing the compounds are disclosed as well as methods for utilizing the compounds to induce antineoplastic and antihyperlipidemic activity.Type: GrantFiled: June 9, 1989Date of Patent: June 11, 1991Assignee: Boron Biologicals, Inc.Inventors: Bernard F. Spielvogel, Anup Sood