Plural Ring Oxygens In The Tricyclo Ring System Patents (Class 549/282)
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Patent number: 6313320Abstract: The present invention concerns compounds of the formula wherein R1, R2, R3, R4 and R6 each represent H or an organic group of up to 20 C atoms, or any pair of R2 and R3 or R2 and R6 or R4 and R6 forms a cyclic group, and R5SO2 is a cleavable protecting group in which R5 is an organic group of up to 20 C atoms. These compounds are useful as intermediates in the synthesis of calanolide A and related antiviral compounds.Type: GrantFiled: April 25, 2000Date of Patent: November 6, 2001Assignee: Chirotech Technology, Inc.Inventors: Martin Edward Fox, Graham Andrew Meek
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Patent number: 6255324Abstract: 5′-substituted, 4′,5′-dihydropsoralen compounds (5) bearing tertiary amines (and salts thereof), quaternary ammonium moieties or organomercurial moieties are described. Also described are 2-substituted mercurimethyl-2-3-dihydro-benzofurans of forumla (7): Also reported are versatile direct syntheses through a hitherto unknown compounds such as 3-R-4,8-dimethyl-4′,5′-dihydro-5′-bromomethylpsoralen or a 3-R-4,8-dimethyl-4′, 5′-dihydro-5′-iodomethylpsoralen to prepare a structurally diverse array of partially reduced psoralens and benzofurans. The presence of a permanent ammonium charge in these psoralens precludes membrane passage and the mono-unsaturation precludes the cross-linking of nuclear DNA, thereby minimizing the mutagenic/carcinogenic side effects long associated with psoralen-derived therapies.Type: GrantFiled: November 25, 1998Date of Patent: July 3, 2001Inventors: Ned D. Heindel, Jeffrey D. Laskin, Diane E. Heck, Robert D. Rapp, Marilyn S. Whittemore, Thomas E. McNeel, Ivan Jabin
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Patent number: 6255337Abstract: First-pass effective substances derived from citrus.Type: GrantFiled: May 27, 1999Date of Patent: July 3, 2001Assignee: Bioavailability Systems, L.L.C.Inventor: James W. Harris
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Patent number: 6177424Abstract: The invention relates to 4′-substituted-4′,5′-dihydropsoralen compounds of formula(V): In the formula R is hydrogen, a halogen, CN or an acyl group; T is a halogen, CN, a carboalkoxy group NR1R2, or (N+R1R2R3)X−, R1 and R2 are independently a C1-C6 alkyl, or R1 and R2 together with the nitrogen form a 5-8 member heterocyclic ring, or when T is (N+R1R2R3)X−, R1 and R2 together with the nitrogen form a 5-8 member heterocyclic ring or heterocyclic aromatic ring; R3 is hydrogen, a C1-C12 alkyl, or, when R1 and R2 together with the nitrogen form a heterocyclic aromatic ring, R3 is a double bond within the heterocyclic aromatic ring; X− is a halide. In another embodiment, the invention relates to processes for preparing 4′-substituted-4′,5′-dihydropsoralen compounds described above.Type: GrantFiled: November 30, 1999Date of Patent: January 23, 2001Inventors: Ned D. Heindel, Jeffrey D. Laskin, Marilyn S. Whittemore, Thomas E. McNeel, Christophe Guillon, Diane E. Heck, Robert D. Rapp
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Patent number: 6169109Abstract: Viral and bacterial contaminants present in biological solutions are inactivated by mixing one of a novel class of photosensitizer with said solution and irradiating the mixture.Type: GrantFiled: September 4, 1998Date of Patent: January 2, 2001Assignee: Baxter International Inc.Inventors: Sang Chul Park, Raymond P. Goodrich, Jr., Nagender Yerram, Samuel O. Sowemimo-Coker, Matthew S. Platz, Brian M. Aquila
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Patent number: 6160006Abstract: The present invention provides a composition and methods for inhibiting cytochrome P450 enzyme activity and in particular, inhibiting the activity of the cytochrome P450 3A sub-family of enzymes, specifically, CYP3A4. The present invention provides 6',7'-dihydroxybergamottin, a furanocoumarin, as the compound primarily responsible for the inhibitory effects of grapefruit juice on cytochrome P450 enzyme activity. The present invention also provides a novel synthesis scheme for 6',7'-dihydroxybergamottin.Type: GrantFiled: October 16, 1997Date of Patent: December 12, 2000Assignee: Wayne State UniversityInventors: David J. Edwards, Patrick M. Woster
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Patent number: 6133460Abstract: Psoralen compound compositions are synthesized which have primaryamino substitutions on the 3-, 4-, 5-, and 8- positions of the psoralen, which yet permit their binding to nucleic acid of pathogens. Reaction conditions that photoactivate these psoralens result in the inactivation of pathogens which contain nucleic acid. The compounds show similar activity in test systems to 4' and 5' derivatives of psoralen useful for inactivation of pathogens in blood products. In addition to the psoralen compositions, the invention contemplates such inactivating methods using the new psoralens.Type: GrantFiled: November 20, 1998Date of Patent: October 17, 2000Assignee: Cerus CorporationInventors: Susan Wollowitz, Aileen Nerio
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Patent number: 6124477Abstract: The present inventor has discovered chemical compounds which inhibit the first-pass effect of orally administered drugs in humans; that phototoxic low molecular weight furocoumarins and certain ether-substituted furocoumarins that are naturally present in citrus extracts, juices, byproducts, etc. may be removed therefrom or reduced in concentration without destroying the first-pass effect inhibiting compounds therein, and a method for preparing citrus-based compositions using only FDA or USP acceptable reagents.Type: GrantFiled: December 30, 1997Date of Patent: September 26, 2000Assignee: Bioavailability Systems, LLCInventor: James W. Harris
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Patent number: 6054449Abstract: A broad class of photosensitive compounds having enhanced in vivo target tissue selectivity and versatility in photodynamic therapy. Many furocoumarin compounds, such as psoralens, exhibit cytostatic activity when photoactivated but exhibit little in vivo specificity for selectively accumulating in any particular target tissue such as atheromatous plaques. Reactive Oxygen Producing Photosensitizers ("ROPPs") are photoactivatable compounds having an affinity for hyperproliferating cells (such as atheromatous plaque cells), which when photoactivated, produce cytotoxic reaction products. The photoactivity of a ROPP, such as a porphyrin, may be reduced by metalating the porphyrin while the selective affinity of the metalized ROPP for hyperproliferating tissue remains substantially unchanged.Type: GrantFiled: February 14, 1997Date of Patent: April 25, 2000Assignee: Miravant Pharmaceuticals, Inc.Inventors: Byron Robinson, Alan R. Morgan, Hugh L. Narciso, Jr.
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Patent number: 6043271Abstract: A method of preparing (.+-.)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. Useful intermediates for preparing (.+-.)-calanolide A and its derivatives are also provided. According to the disclosed method, chromene 4 intermediate was reacted with acetaldehyde diethyl acetal or paraldehyde in the presence of an acid catalyst with heating, or a two-step reaction including an aldol reaction with acetaldehyde and cyclization either under acidic conditions or neutral Mitsunobu conditions, to produce chromanone 7. Reduction of chromanone 7 with sodium borohydride, in the presence of cerium trichloride, produced (.+-.)-calanolide A. A method for resolving (.+-.)-calanolide A into its optically active forms by a chiral HPLC system or by enzymatic acylation and hydrolysis is also disclosed. Finally, a method for treating or preventing a viral infections using (.+-.)-calanolide or (-)-calanolide is provided.Type: GrantFiled: August 2, 1995Date of Patent: March 28, 2000Assignee: Sarawak MediChem Pharmaceuticals, Inc.Inventors: Michael T. Flavin, Ze-Qi Xu, John D. Rizzo, Alla Kucherenko, Albert Khilevich, Abram Kivovich Sheinkman, Vilayphone Vilaychack, Lin Lin, Wei Chen, William A. Boulanger
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Patent number: 6017691Abstract: Psoralen compounds are synthesized which have substitutions on the 4, 4', 5', and 8 positions of the psoralen, which permit enhanced binding to nucleic acid of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention contemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion.Type: GrantFiled: February 9, 1996Date of Patent: January 25, 2000Assignee: Cerus CorporationInventors: Susan Wollowitz, Stephen T. Isaacs, Henry Rapoport, Hans Peter Spielmann, Aileen Nerio
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Patent number: 5990154Abstract: This invention relates to the process of making citrus (preferably grapefruit) extract having reduced levels of phototoxic furocoumarins and containing enhanced amounts of one or more anti-first pass effect compounds.Type: GrantFiled: May 22, 1998Date of Patent: November 23, 1999Assignee: Bioavailability Systems, L.L.C.Inventor: James W. Harris
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Patent number: 5981770Abstract: A method of preparing (+)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. According to the disclosed method, chromene 4 intermediate was subjected to a chlorotitanium-mediated aldol reaction with acetaldehyde to selectively produce (.+-.)-8a. Separation and enzyme-mediated resolution of (.+-.)-8a produced (+)-8a. Cyclization of (+)-8a under neutral Mitsunobu conditions followed by Luche reduction of (+)-7 produced (+)-calanolide A in high yield and enantiomeric purity. The method of the invention has been extended to produce potent antiviral calanolide A analogues.Type: GrantFiled: September 5, 1997Date of Patent: November 9, 1999Assignee: Sarawak MediChem Pharmaceuticals, Inc.Inventors: Michael T. Flavin, Ze-Qi Xu, Albert Khilevich, David Zembower, John D. Rizzo, Shuyuan Liao, Aye Mar, Lin Lin, Vilayphone Vilaychack, Darko Brankovic, Sergey Dzekhster, Jinjun Liu
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Patent number: 5981495Abstract: The present invention offers a safe and effective drug for heart diseases and a safe and effective method for treating heart diseases such as ischemic heart disease and cardiac arrhythmia. The method comprises administering a pathologically effective amount of a benzopyran derivative expressed by the following general formula (I): ##STR1## wherein R.sup.1 is an alkyl group or an alkenyl group, R.sup.2 is a hydrogen atom, an alkyl group, an alkyl group having at least one hydroxyl group, an alkenyl group, an acyl group or a glycosyl group; or physiologically acceptable salts thereof.Type: GrantFiled: March 19, 1997Date of Patent: November 9, 1999Assignee: Dainippon Ink and Chemicals, Inc.Inventors: Hidetsugu Takagaki, Nobuyuki Kimura, Yasuo Aoki, Shigenori Nakanishi, Masayoshi Abe, Osamu Misumi
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Patent number: 5977385Abstract: A method of preparing (+)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. According to the disclosed method, chromene 4 intermediate was subjected to a chlorotitanium-mediated aldol reaction with acetaldehyde to selectively produce (.+-.)-8a. Separation and enzyme-mediated resolution of (.+-.)-8a produced (+)-8a. Cyclization of (+)-8a under neutral Mitsunobu conditions followed by Luche reduction of (+)-7 produced (+)-calanolide A in high yield and enantiomeric purity. The method of the invention has been extended to produce potent antiviral calanolide A analogues.Type: GrantFiled: July 15, 1998Date of Patent: November 2, 1999Assignee: Sarawak MediChem PharmaceuticalsInventors: Michael T. Flavin, Ze-Qi Xu, Albert Khilevich, David Zembower, John D. Rizzo, Shuyuan Liao, Aye Mar, Lin Lin, Vilayphone Vilaychack, Darko Brankovic, Sergey Dzekhster, Jinjun Liu
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Patent number: 5958970Abstract: This invention provides cancer-active tricyclic and tetracyclic oxypyrones and a method of synthesizing these compounds. Preferred compounds have aryl groups at the 3-position of the oxypyrone ring. The tricyclic oxyprone synthetic method is a simple condensation reaction of pyrones with cyclohexenecarboxaldehydes, providing high yields and using few steps. The tetracyclic oxypyrone synthetic method is a simple condensation reaction of carvones with pyrones.Type: GrantFiled: July 29, 1997Date of Patent: September 28, 1999Assignee: Kansas State University Research FoundationInventors: Duy H. Hua, Jean-Pierre Perchellet
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Patent number: 5929108Abstract: The present invention concerns photochemical labelling reagents comprising a digoxigenin derivative and a furocoumarin derivative bound via a spacer. The labelling reagent can be used in gene diagnostic.Type: GrantFiled: March 31, 1997Date of Patent: July 27, 1999Assignee: Bayer AktiengesellschaftInventors: Antonius Lobberding, Gamal K. Mikhail, Wolfgang Springer
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Patent number: 5919935Abstract: The present invention relates to novel, halogenated psoralen compounds that are useful for inactivating vital contaminants in blood-derived products, particularly blood-derived products that contain platelets or red blood cells. The psoralen compounds of the present invention have the following formula: The side chain S which is a attached to the carbon at position 8 of the psoralen moiety contains a quartemary ammonium group which comprises a central nitrogen atom, a linking group L, and an aromatic ring structure. The linking group L joins the central nitrogen atom of the quartenary ammonium group to the psoralen moiety. The linking group L comprises a carbon chain having 2 to 12 carbon atoms and an oxygen atom which links the carbon chain to the psoralen moiety. The psoralen compounds of the present invention also comprise one or more halogens attached to the psoralen moiety. Preferably the halogens are attached to the carbon atom at position 3 or 5 of the psoralen moiety.Type: GrantFiled: November 21, 1997Date of Patent: July 6, 1999Assignee: The Ohio State Research FoundationInventors: Matthew S. Platz, Tongqian Chen, Shashi S. Kagan, Helena M. Pereira
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Patent number: 5874591Abstract: A method of preparing (.+-.)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. Useful intermediates for preparing (.+-.)-calanolide A and its derivatives are also provided. According to the disclosed method, chromene 4 intermediate was reacted with acetaldehyde diethyl acetal or paraldehyde in the presence of an acid catalyst with heating, or a two-step reaction including an aldol reaction with acetaldehyde and cyclization either under acidic conditions or neutral Mitsunobu conditions, to produce chromanone 7. Reduction of chromanone 7 with sodium borohydride, in the presence of cerium trichloride, produced (.+-.)-calanolide A. A method for resolving (.+-.)-calanolide A into its optically active forms by a chiral HPLC system or by enzymatic acylation and hydrolysis is also disclosed. Finally, a method for treating or preventing viral infections using (.+-.)-calanolide A or (-)-calanolide A is provided.Type: GrantFiled: September 9, 1997Date of Patent: February 23, 1999Assignee: Sarawak MediChem Pharmaceuticals, Inc.Inventors: Michael T. Flavin, Ze-Qi Xu, Vilayphone Vilaychack, Lin Lin
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Patent number: 5871900Abstract: Psoralen compounds are synthesized which have substitutions on the 4, 4', 5', and 8 positions of the psoralen, which permit enhanced binding to nucleic acid of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention compemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion. In particular, 5'-primary amino psoralens are photoactivated in order to inactivate pathogens in biological fluids.Type: GrantFiled: November 7, 1997Date of Patent: February 16, 1999Assignee: Cerus CorporationInventors: Susan Wollowitz, Stephen T. Isaacs, Henry Rapoport, Hans Peter Spielmann, Aileen Nerio
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Patent number: 5847165Abstract: Disclosed are compounds of Formula I: ##STR1## wherein R.sup.1 through R.sup.6 are defined herein. Also disclosed are pharmaceutical compositions and methods of using these compositions for treating retroviral infections. Finally, a stereoselective method for synthesizing compounds of Formula I is described.Type: GrantFiled: February 21, 1996Date of Patent: December 8, 1998Assignee: The University of North Carolina at Chapel HillInventors: Kuo-Hsiung Lee, Mark Cosentino, Lan Xie, Mark Manak
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Patent number: 5847164Abstract: A method of preparing (.+-.)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. Useful intermediates for preparing (.+-.)-calanolide A and its derivatives are also provided. According to the disclosed method, chromene 4 intermediate was reacted with acetaldehyde diethyl acetal or paraldehyde in the presence of an acid catalyst with heating, or a two-step reaction including an aldol reaction with acetaldehyde and cyclization either under acidic conditions or neutral Mitsunobu conditions, to produce chromanone 7. Reduction of chromanone 7 with sodium borohydride, in the presence of cerium trichloride, produced (.+-.)-calanolide A. A method for resolving (.+-.)-calanolide A into its optically active forms by a chiral HPLC system or by enzymatic acylation and hydrolysis is also disclosed. Finally, a method for treating or preventing viral infections using (.+-.)-calanolide A or (-)-calanolide A is provided.Type: GrantFiled: September 9, 1997Date of Patent: December 8, 1998Assignee: Sarawak MediChem Pharmaceuticals, Inc.Inventors: Michael T. Flavin, Ze-Qi Xu, John D. Rizzo, Albert Khilevich, Abram Kivovich Sheinkman
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Patent number: 5843990Abstract: The invention relates to pyran-chromenone compounds, their synthesis and anti-HIV activity. Methods of synthesis are disclosed; the compounds have activity against reverse transcriptase. Biological compositions containing the compounds and method of treating patients are also disclosed.Type: GrantFiled: December 23, 1996Date of Patent: December 1, 1998Assignee: The University of Tennessee Research CorporationInventor: David Baker
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Patent number: 5840921Abstract: A method of preparing (.+-.)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. Useful intermediates for preparing (+)-calanolide A and its derivatives are also provided. According to the disclosed method, chromene 4 intermediate was reacted with acetaldehyde diethyl acetal or paraldehyde in the presence of an acid catalyst with heating, or a two-step reaction including an aldol reaction with acetaldehyde and cyclization either under acidic conditions or neutral Mitsunobu conditions, to produce chromanone 7. Reduction of chromanone 7 with sodium borohydride, in the presence of cerium trichloride, produced (.+-.)-calanolide A. A method for resolving (.+-.)-calanolide A into its optically active forms by a chiral HPLC system or by enzymatic acylation and hydrolysis is also disclosed. Finally, a method for treating or preventing viral infections using (.+-.)-calanolide A or (-)-calanolide A is provided.Type: GrantFiled: September 9, 1997Date of Patent: November 24, 1998Assignee: Sarawak MediChem Pharmaceuticals, Inc.Inventors: Michael T. Flavin, Ze-Qi Xu, John D. Rizzo, Albert Khilevich
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Patent number: 5773609Abstract: A broad class of photosensitive compounds having enhanced in vivo target tissue selectivity and versatility in photodynamic therapy. Many furocoumarin compounds, such as psoralens, exhibit cytostatic activity when photoactivated but exhibit little in vivo specificity for selectively accumulating in any particular target tissue such as atheromatous plaques. Reactive Oxygen Producing Photosensitizers ("ROPPs") are photoactivatable compounds having an affinity for hyperproliferating cells (such as atheromatous plaque cells), which when photoactivated, produce cytotoxic reaction products. The photoactivity of a ROPP, such as a porphyrin, may be reduced by metalating the porphyrin while the selective affinity of the metalized ROPP for hyperproliferating tissue remains substantially unchanged.Type: GrantFiled: February 14, 1997Date of Patent: June 30, 1998Assignee: PDT Pharmaceuticals, Inc.Inventors: Byron Robinson, Alan R. Morgan, Hugh L. Narciso, Jr.
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Patent number: 5736563Abstract: A method destroys or impairs target cells that have selectively accumulated a photosensitizing agent. The target cells are in the bloodstream of an intact animal, which bloodstream and animal further contain non-target cells. Radiation is applied transcutaneously to at least a portion of the intact animal at an intensity effective to impair or destroy selectively the target cells and to leave non-target cells relatively unimpaired. Target cells include leukemia cells, virus-containing cells, parasite-containing cells, and microorganisms such as bacteria, parasites and free viruses.Type: GrantFiled: November 8, 1995Date of Patent: April 7, 1998Assignee: Quadra Logic Technologies, Inc.Inventor: Anna M. Richter
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Patent number: 5726204Abstract: The present invention is directed to compounds that are analogs of the natural product suksdorfin. Compounds of the present invention include those having Formula I: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are defined herein. The invention is also directed to methods of making these compounds, pharmaceutical compositions including these compounds and methods of using the compounds to inhibit retroviral infections in cells and tissues of animals. A method for stereoselectively preparing compounds within the scope of the invention by catalytic asymmetric dihydroxylation is also disclosed.Type: GrantFiled: June 5, 1995Date of Patent: March 10, 1998Assignees: Biotech Research Laboratories, University of North Carolina at Chapel HillInventors: Kuo-Hsiung Lee, Yoshiki Kashiwada, Li Huang, Thomas Tung-Ying Lee, Mark Cosentino, Jim Snider, Mark Manak, Lan Xie
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Patent number: 5712085Abstract: Psoralen compounds are synthesized which have substitutions on the 4,4',5', and 8 positions of the psoralen, which permit enhanced binding to nucleic acid of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention contemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion. Also disclosed are compositions comprising 4' or 5'-primary amino substituted psoralens in a synthetic media.Type: GrantFiled: June 5, 1995Date of Patent: January 27, 1998Assignee: Cerus CorporationInventors: Susan Wollowitz, Stephen T. Isaacs, Henry Rapoport, Hans Peter Spielmann, Aileen Nerio
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Patent number: 5686485Abstract: The present invention relates to EI-1941 compounds having interleukin-1 production inhibitory activity which are represented by the formula: ##STR1## wherein either of R.sup.1 and R.sup.2 is hydrogen and the other is hydroxy, or R.sup.1 and R.sup.2 together represent oxygen; and R.sup.3 is hydroxy and R.sup.4 is hydrogen, or R.sup.3 and R.sup.4 together represent --0--.Type: GrantFiled: October 9, 1996Date of Patent: November 11, 1997Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Takeo Tanaka, Hidemasa Kondo, Fumito Koizumi, Hiroki Ishiguro, Mayumi Yoshida, Katsuhiko Ando, Yuzuru Matsuda
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Patent number: 5659050Abstract: The present invention contemplates methods of decontaminating human fluids prior to processing in the clinical laboratory. The techniques handle large volumes of human serum without impairing the testing results. Novel compounds for photodecontaminating biological material are also contemplated which are compatible with clinical testing, in that they do not interfere with serum analytes.Type: GrantFiled: June 5, 1995Date of Patent: August 19, 1997Assignee: Cerus CorporationInventors: Stephen T. Isaacs, George D. Cimino
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Patent number: 5654443Abstract: Psoralen compound compositions are synthesized which have substitutions on the 4, 4', 5', and 8 positions of the psoralen, which yet permit their binding to nucleic acid of pathogens. Reaction conditions that photoactivate these bound psoralens result in covalent crosslinking to nucleic acid, thereby inactivating the pathogen. Higher psoralen binding levels and lower mutagenicity results in safer, more efficient, and reliable inactivation of pathogens. In addition to the psoralen compositions, the invention contemplates inactivating methods using the new psoralens.Type: GrantFiled: May 31, 1995Date of Patent: August 5, 1997Assignee: Cerus CorporationInventors: Susan Wollowitz, Stephen T. Isaacs, Henry Rapoport, Hans Peter Spielmann
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Patent number: 5625079Abstract: Synthesis of 4,8-dialkyl-4'-bromomethyl-5'-methylpsoralen and 4,8-dialkyl-5'-bromomethyl-4'-methylpsoralen compounds useful as intermediates.Type: GrantFiled: June 5, 1995Date of Patent: April 29, 1997Assignee: Cerus CorporationInventors: Susan Wollowitz, Stephen T. Isaacs, Henry Rapoport, Hans P. Spielmann, Aileen Nerio
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Patent number: 5616731Abstract: The present invention concerns photochemical labelling reagents comprising a digoxigenin derivative and a furocoumarin derivative bound via a spacer. The labelling reagent can be used in gene diagnostic.Type: GrantFiled: June 6, 1995Date of Patent: April 1, 1997Assignee: Bayer AktiengesellschaftInventors: Antonius L obberding, Gamal K. Mikhail, Wolfgang Springer
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Patent number: 5587490Abstract: A compound is provided for inactivating viral, bacterial or other contamination in cells, body fluids or fractions thereof. The compound comprises a psoralen with a single substituent that is either a quaternary phosphonium or ammonium moiety, and at least one substituent that is a halogen. The compound selectively binds to the contaminant, and upon activation by irradiation, damages the contaminant.Type: GrantFiled: December 10, 1993Date of Patent: December 24, 1996Assignee: Credit Managers Association of CaliforniaInventors: Raymond P. Goodrich, Jr., Matthew S. Platz, Nagender Yerram, Roger W. Hackett, Marjan van Borssum Waalkes, Christine M. Williams-Hughes, Victoria A. Wong
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Patent number: 5585503Abstract: Psoralen compound compositions are synthesized which have substitutions on the 4, 4', 5', and 8 positions of the psoralen, which yet permit their binding to nucleic acid of pathogens. Reaction conditions that photoactivate these bound psoralens result in covalent crosslinking to nucleic acid, thereby inactivating the pathogen. Higher psoralen binding levels and lower mutagenicity results in safer, more efficient, and reliable inactivation of pathogens. In addition to the psoralen compositions, the invention contemplates inactivating methods using the new psoralens.Type: GrantFiled: May 31, 1995Date of Patent: December 17, 1996Assignee: Steritech, Inc.Inventors: Susan Wollowitz, Stephen T. Isaacs, Henry Rapoport, Hans P. Spielmann
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Patent number: 5578736Abstract: Psoralen compound compositions are synthesized which have substitutions on the 4, 4', 5', and 8 positions of the psoralen, which yet permit their binding to nucleic acid of pathogens. Reaction conditions that photoactivate these bound psoralens result in covalent crosslinking to nucleic acid, thereby inactivating the pathogen. Higher psoralen binding levels and lower mutagenicity results in safer, more efficient, and reliable inactivation of pathogens. In addition to the psoralen compositions, the invention contemplates inactivating methods using the new psoralens.Type: GrantFiled: May 31, 1995Date of Patent: November 26, 1996Assignee: Steritech, Inc.Inventors: Susan Wollowitz, Stephen T. Isaacs, Henry Rapoport, Hans P. Spielmann
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Patent number: 5559250Abstract: Novel compounds for photodecontaminating biological material which are compatible with clinical testing, in that they do not interfere with serum analytes.Type: GrantFiled: June 5, 1995Date of Patent: September 24, 1996Assignee: Steritech, Inc.Inventors: David Cook, Susan Wollowitz, Aileen Nerio
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Patent number: 5556993Abstract: Psoralen compounds are synthesized which have substitutions on the 4,4', 5', and 8 positions of the psoralen, which permit enhanced binding to nucleic acid of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention contemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion.Type: GrantFiled: June 5, 1995Date of Patent: September 17, 1996Assignee: Steritech, Inc.Inventors: Susan Wollowitz, Stephen T. Isaacs, Henry Rapoport, Hans P. Spielmann, Aileen Nerio
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Patent number: 5489697Abstract: A method for preparing (.+-.)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. Useful intermediates for preparing (.+-.)-calanolide A and its derivatives are also provided.According to the disclosed method, chromene 4 intermediate was reacted with acetaldehyde diethyl acetal in the presence of an acid catalyst with heating to produce chromanone 7. Reduction of chromene 7 with sodium borohydride, in the presence of cerium trichloride, produced (.+-.)-calanolide A, which was purified chromatographically.Type: GrantFiled: August 3, 1994Date of Patent: February 6, 1996Assignee: MediChem Research, Inc.Inventors: William A. Boulanger, Michael T. Flavin, Alla Kucherenko, Abram K. Sheynkman
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Patent number: 5473083Abstract: The invention features phototherapeutic compositions comprising Type 1, Type 2, or Type 3 psoralens and methods of using such compounds for treatment of proliferative diseases of skin, blood and bone marrow.Type: GrantFiled: September 2, 1994Date of Patent: December 5, 1995Assignees: Lehigh University, University of Medicine and Dentistry of New JerseyInventors: Ned D. Heindel, Jeffrey D. Laskin
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Patent number: 5399719Abstract: Psoralen compound compositions are synthesized which have substitutions on the 4, 4', 5', and 8 positions of the psoralen, which yet permit their binding to nucleic acid of pathogens. Reaction conditions that photoactivate these bound psoralens result in covalent crosslinking to nucleic acid, thereby inactivating the pathogen. Higher psoralen binding levels and lower mutagenicity results in safer, more efficient, and reliable inactivation of pathogens. In addition to the psoralen compositions, the invention contemplates inactivating methods using the new psoralens.Type: GrantFiled: June 28, 1993Date of Patent: March 21, 1995Assignee: Steritech, Inc.Inventors: Susan Wollowitz, Stephen T. Isaacs, Henry Rapoport, Hans P. Spielmann
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Patent number: 5216176Abstract: A photochemotherapeutic compound of the formula ##STR1## wherein (i) n is zero, W is a (C.sub.1-16) alkyl, alkenyl, or alkynyl linear or branched chain hydrocarbon, having no more than four O, N, or S atoms in or attached to the chain; or(ii) n is 1, W is CR or CR.sub.2, and R, R', and R" are independently H or CH.sub.3 ; or(iii) N is 2, W is CR or CR.sub.2, and R, R', and R" are independently H or CH.sub.3 ; andA, B, C, and D are independently selected from hydrogen, alkyl, aryl, halogen, amino, aminoalkyl, nitro, alkoxy, aryloxy, hydroxy, carboxy, haloalkyl, or haloalkoxy, particularly compounds of the foregoing structure in which W is a charged substiuent and n=0 or 1.Type: GrantFiled: December 21, 1990Date of Patent: June 1, 1993Assignee: Lehigh UniversityInventors: Ned D. Heindel, Michele C. Jetter nee Siller, Jeffrey D. Laskin, Michael A. Gallo
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Patent number: 5216014Abstract: The present invention provides novel furocoumarinsufonamide derivatives having the formula ##STR1## wherein R.sub.1, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are independently H or lower alkyl; m, n and p are independently 2, 3, 4, 5 or 6; A is NR.sub.4 (CH.sub.2).sub.P NR.sub.5, NR.sub.6, O or S; R.sub.2 is independently H, lower alkyl or a moiety of the formula ##STR2## useful for inhibiting protein kinase C and treating conditions related to, or affected by inhibition of protein kinase C, particularly cancer tumors, inflammatory disease, reperfusion injury, and cardiac dysfunctions related to reperfusion injury.Type: GrantFiled: September 10, 1991Date of Patent: June 1, 1993Assignee: Sphinx Pharmaceuticals CorporationInventors: Jack B. Jiang, Mary G. Johnson
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Patent number: 5200425Abstract: This invention relates to improvements to drugs containing as an active substance the 5-methoxypsoralene of formula: ##STR1##Type: GrantFiled: November 1, 1990Date of Patent: April 6, 1993Inventor: Jean-Jacques Goupil
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Patent number: 5179092Abstract: A compound having the formula (I): ##STR1## wherein A is --CH.sub.2 --, --O--, or --S--; R.sup.1 is CH.sub.3 or OCH.sub.3 ; R.sup.2 is hydroxy or carboxy which may be optionally esterized or amidated; R.sup.3 is H or a lower alkyl; and n is 0 or an integer of 1 to 6 or a pharmaceutically acceptable salt thereof.Type: GrantFiled: July 30, 1991Date of Patent: January 12, 1993Assignee: Suntory LimitedInventors: Toshio Tatsuoka, Kenji Suzuki, Fumio Satoh, Seiji Miyano, Kunihiro Sumoto
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Patent number: 5179217Abstract: The alkylangelicins according to the invention are obtained starting from an umbelliferone, in which the 6-position is already substituted by an alkyl group; in such a way the 7-allyloxy or 7-acyloxy umbelliferone intermediates can form by transposition of the allyl or acyl group only the 8-allyl and 8-acyl derivatives, and therefore the presence, even in traces, of psoralens is absolutely excluded in the subsequent synthetic steps.The 6-alkylangelicins thus obtained are particularly usable for the photochemotherapy of psoriasys and of other skin diseases characterized by cellular hyperproliferation, as well as for the photochemotherapy of vitiligo and of alopecia aerata.Type: GrantFiled: December 27, 1990Date of Patent: January 12, 1993Inventors: Francarosa Baccichetti, Franco Bordin, Carlo Monti-Bragadin, Francesco Carlassare, Giovanni Recchia, Giovanni Rodighiero, Paolo Rodighiero, Daniela Vedaldi, Mario Cristofolini, Francesco Dall'Acqua, Adriano Guiotto, Giovanni Pastorini
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Patent number: 5028720Abstract: The present invention relates to novel benzopyranone aci-reductone compounds of the formula I wherein X and Y are selected from the group comprising H (except that X and Y are not both H, unless otherwise indicated) Cl or other halogen, OH, a straight or branched C.sub.1 14 C.sub.6 alkyl or alkoxy group or phenyl or phenyloxy groups, such as, for example a phenyl or a tertiary butyl group. The invention also provides for compounds of the general formula I wherein X, Y.dbd.OCH.sub.2 O.Type: GrantFiled: June 2, 1989Date of Patent: July 2, 1991Assignee: Ohio State University Research FoundationInventors: Donald T. Witiak, Sung K. Kim, Dennis R. Feller, Karl J. Romstedt
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Patent number: 4970230Abstract: This invention relates to improvements to drugs containing as an active substance the 5-methoxypsoralene of formula: ##STR1##Type: GrantFiled: August 9, 1989Date of Patent: November 13, 1990Inventor: Jean-Jacques Goupil
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Patent number: 4950770Abstract: A direct, acid-catalyzed substitution reaction incorporates an N-phthalimidomethyl group on the 4' or 5' carbon of a psoralen in yields of 60-80% via the condensation of an N-hydroxymethylamide or phthalimide (e.g. N-hydroxymethylphthalimide) and an appropriately substituted psoralen. The phthalimide moiety is cleaved from the psoralen ring by treatment with hydrazine to give 60 to 70% yields of the aminomethylpsoralens.Type: GrantFiled: July 14, 1988Date of Patent: August 21, 1990Assignee: Elder Pharmaceuticals, Inc.Inventors: Ned D. Heindel, Mridula D. Choudhuri
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Patent number: 4950744Abstract: A photochemical nucleic acid-labeling reagent of the formula ##STR1## wherein Q is a photoreactive residue of a nucleic acid-binding ligand; L is a detectable label residue; R is hydrogen, C.sub.1 to C.sub.7 -alkyl, aryl, hydroxy, or C.sub.1 to C.sub.7 -alkoxy; x is an integer from 2 through 7; and y is an integer from 3 through 10; wherein R and x, respectively, can be the same or different each time they appear in the formula. The reagent is useful in the highly efficient labeling of nucleic acids for the purpose of detection in hybridization assays.Type: GrantFiled: March 18, 1987Date of Patent: August 21, 1990Assignee: Molecular Diagnostics, Inc.Inventors: Nanibhushan Dattagupta, James P. Albarella