Plural Phosphori Bonded Directly To The Same Carbon Patents (Class 562/21)
  • Patent number: 9315524
    Abstract: The present invention discloses magnetic resonance compatible contrast agents for water-poor structures, such as bone and tissue calcification. In particular, the present invention discloses bisphosphonate-based magnetic resonance imaging contrast agents specific for hydroxyapatite, the calcium salt most commonly associated with malignant calcification.
    Type: Grant
    Filed: May 7, 2012
    Date of Patent: April 19, 2016
    Inventor: Kumar Ranjan Bhushan
  • Patent number: 8853187
    Abstract: The present invention relates to a composition for prevention and/or treatment of metabolic diseases of bones comprising at least one bisphosphonate; viscosity agents comprising carboxymethylcellulose and xanthan gum; at least one flavoring agent; and purified water; a process for preparing a composition according to the present invention; and use of such a composition for prevention, treatment and/or diagnosis of metabolic diseases of bones, especially for children.
    Type: Grant
    Filed: June 8, 2009
    Date of Patent: October 7, 2014
    Assignees: Gador S.A., University of Leiden
    Inventors: Daniel Zanetti, Damian Cairatti, Enrique Piccinni, Emilio J. A. Roldan, Socrates Papapoulos
  • Patent number: 8802123
    Abstract: Endosseous implant to be applied to a human or animal bone, wherein the surface of the implant is made from titanium or a titanium alloy, said implant having a smooth or rough surface texture, which is characterized in that said surface has been treated with at least one selected organic phosphonate compound or a pharmaceutically acceptable salt or ester or an amide thereof; process for producing said implants.
    Type: Grant
    Filed: June 8, 2012
    Date of Patent: August 12, 2014
    Assignees: Universite de Geneve, Ecole Polytechnique Federale de Lausanne
    Inventors: Pierre Descouts, Björn-Owe Aronsson, Michael Grätzel, Carine Viornery, Peter Péchy
  • Patent number: 8778914
    Abstract: The present invention relates to a prodrug, comprising a pharmaceutically and/or diagnostically active compound, and one or more bisphosphonate groups, to a process for producing such a prodrug, and to a pharmaceutical composition comprising said prodrug, to be used for the treatment of bone-related disorders such as bone cancer.
    Type: Grant
    Filed: August 24, 2010
    Date of Patent: July 15, 2014
    Assignee: KTB Tumorforschungsgesellschaft mbH
    Inventors: Felix Kratz, Katrin Hochdoerffer
  • Patent number: 8748410
    Abstract: The present invention is directed to a method for treating aneurysms in vascular tissue. The method includes administering a bisphosphonate compound to a subject in an amount which is effective against the formation or progression of aneurysm, or which is effective to induce regression of an established aneurysm. In alternative methods, an anti-RANKL neutralizing antibody is administered to the subject to achieve analogous anti-aneurysm effect. The methods of particular advantage in the treatment of subjects having an abdominal aortic aneurysm, a relatively common, and life-threatening, condition.
    Type: Grant
    Filed: September 9, 2011
    Date of Patent: June 10, 2014
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Dai Yamanouchi, K. Craig Kent, Bo Liu
  • Patent number: 8741809
    Abstract: The present invention relates to a novel liquid formulation for crop protection which comprises a) pyraclostrobin; b) at least one organic solvent S1 with a water solubility of less than 2 g/l at 20° C.; c) at least one organic solvent S2 with a water solubility of at least 2 g/l at 20° C., where S2 comprises at least one solvent S2.1 with a water solubility of more than 200 g/l at 20° C. and optionally at least one solvent S2.2 with a water solubility of 2 to 200 g/l at 20° C.; d) at least one anionic surface-active substance SA1; e) at least one nonionic surface-active substance SA2; and f) water. The invention also relates to the use of the crop protection formulation for treatment of plants and seed, and to corresponding methods.
    Type: Grant
    Filed: October 9, 2009
    Date of Patent: June 3, 2014
    Assignee: BASF SE
    Inventors: Ulrike Troppmann, Wolfgang Meier, Guenter Oetter, Ulrich Steinbrenner, Tatjana Levy, Jurith Montag, Tanja Brunner, Reiner Weiler
  • Patent number: 8586781
    Abstract: The present invention provides novel bisphosphonate conjugates, pharmaceutical compositions comprising bisphosphonate conjugates and methods of using such analogs in the treatment of bone cancer, bone-related diseases, bone infection, bone inflammation, and diseases of the soft tissues surrounding bones.
    Type: Grant
    Filed: March 30, 2009
    Date of Patent: November 19, 2013
    Assignee: MBC Pharma, Inc.
    Inventors: Alexander Karpeisky, Shawn Patrick Zinnen
  • Publication number: 20130131006
    Abstract: The present invention relates to a method for inhibiting the induction of cell death by inhibiting the synthesis or secretion of AGE-albumin in cells of the mononuclear phagocyte system, to an AGE-albumin synthesis inhibitor, and to a pharmaceutical composition comprising the AGE-albumin synthesis inhibitor for preventing or treating degenerative disease and autoimmune disease. The AGE-albumin of the present invention is synthesized and secreted in human microglia or human macrophages in an Alzheimer's model, stroke model, Parkinson's disease model and rheumatoid arthritis model. The AGE-albumin synthesis and secretion are caused by oxidative stress. The expression of RAGE increases in first-order human neurons or cartilage cells to which AGE-albumin is administered, whereupon a MAPK signaling pathway is activated and the expression of Bax increases to induce an increase in calcium in mitochondria, thus finally inducing cell death.
    Type: Application
    Filed: April 28, 2011
    Publication date: May 23, 2013
    Applicant: Gachon University of Industry-Academic Cooperation Foundation
    Inventors: Bong Hee Lee, Kyung Hee Byun
  • Publication number: 20130090494
    Abstract: There is proposed a chemical compound of 5,11,17,23-tetrakis[bis(dihydroxyphosphoryl)methyl]calix[4]arene and a sodium salt thereof, which can be used as antithrombotic agents. A highly specific inhibiting effect of the aforementioned calixarenes on the fibrin polymerization has been identified. It has been found that the addition of the aforementioned calixarenes to blood plasma leads to an increase of the prothrombin time and the activated partial thromboplastin time.
    Type: Application
    Filed: April 11, 2011
    Publication date: April 11, 2013
    Inventors: Serhii Vasyl'ovych Komisarenko, Eduard Vitaliiovych Lugovs'Koi, Pavlo Gryhorovych Grytsenko, Vitalii Ivanovych Kal'Chenko, Tetiana Anatoliivna Koshel', Serhii Oleksiiovych Cherenok, Oleksandr Anatoliiovych Yushchenko, Evhenii Oleksandrovych Kolesnyk
  • Publication number: 20120258148
    Abstract: Endosseous implant to be applied to a human or animal bone, wherein the surface of the implant is made from titanium or a titanium alloy, said implant having a smooth or rough surface texture, which is characterized in that said surface has been treated with at least one selected organic phosphonate compound or a pharmaceutically acceptable salt or ester or an amide thereof; process for producing said implants.
    Type: Application
    Filed: June 8, 2012
    Publication date: October 11, 2012
    Inventors: Pierre DESCOUTS, Björn-Owe ARONSSON, Michael GRÄTZEL, Carine VIORNERY, Peter PÉCHY
  • Patent number: 8269037
    Abstract: An absorption medium for removing acid gases from a fluid stream comprises an aqueous solution of a) of at least one metal salt of an aminocarboxylic acid, and b) of at least one acid promoter, wherein the molar ratio of b) to a) is in the range from 0.0005 to 1.0. The acid promoter is selected from mineral acids, carboxylic acids, sulfonic acids, organic phosphonic acids and partial esters thereof. The absorption medium, compared with absorption media based on amino acid salts, has a reduced regeneration energy requirement without significantly reducing the absorption capacity of the solution for acid gases. In a process for removing acid gases from the fluid stream, the fluid stream is brought into contact with the absorption medium.
    Type: Grant
    Filed: January 28, 2010
    Date of Patent: September 18, 2012
    Assignee: BASF SE
    Inventors: Gerald Vorberg, Torsten Katz, Georg Sieder, Christian Riemann, Rupert Wagner, Ute Lichtfers, Erika Dengler
  • Publication number: 20120165296
    Abstract: The present invention relates to a prodrug, comprising a pharmaceutically and/or diagnostically active compound, and one or more bisphosphonate groups, to a process for producing such a prodrug, and to a pharmaceutical composition comprising said prodrug, to be used for the treatment of bone-related disorders such as bone cancer.
    Type: Application
    Filed: August 24, 2010
    Publication date: June 28, 2012
    Applicant: KTB TUMORFORSCHUNGSGESELLSCHAFT MBH
    Inventors: Felix Kratz, Katrin Hochdoerffer
  • Publication number: 20120028926
    Abstract: This invention relates to methods and small molecules having a phosphate group that can be used to inhibit phosphate transport and to treat or prevent diseases that are related to disorders in the maintenance of normal serum phosphate levels.
    Type: Application
    Filed: January 26, 2010
    Publication date: February 2, 2012
    Applicant: CYTOCHROMA INC.
    Inventors: Uttam Saha, Christian F. Helvig, P. Martin Petkovich
  • Publication number: 20110230447
    Abstract: Disclosed are: a compound which can be produced through a chemical synthesis at low cost, has an excellent osteogenesis-promoting activity, has high affinity for a bone, and can be applied without the need of any special DDS; and a method for promoting osteogenesis by administering the compound and applying the promotion of osteogenesis to the formation or regeneration of a bone. Specifically disclosed are: an osteogenesis promoter or a pharmaceutical composition comprising [4-(methylthio)phenylthio]methanebisphosphonic acid, which is one of bisphosphonic acids, or a pharmaceutically acceptable salt thereof as an active ingredient; and a method for promoting osteogenesis, which comprises administering the osteogenesis promoter or the pharmaceutical composition to a subject to be treated.
    Type: Application
    Filed: August 5, 2009
    Publication date: September 22, 2011
    Applicants: Tohoku University, Showa University
    Inventors: Hisashi Shinoda, Kaoru Igarashi, Shinobu Murakami, Keiko Suzuki
  • Publication number: 20110195876
    Abstract: This invention relates to compounds of formulae (1a) and (1b) wherein R means H or C1- to C6-alkyl, X is a structural unit selected from the formulae wherein m and k mean independently from each other a number from 1 to 12 for (4) and (5) and from 1 to 11 for (6), Y is a structural unit selected from the formulae wherein a, b independently from each other are integers from 1 to 10 R means hydrogen or C1- to C6-alkyl R2 means an alkylene or alkylidene group having 1 to 6 carbon atoms or an arylene or alkylarylene group having from 6 to 20 carbon atoms R3, R4, R5, R6 independently from each other mean an alkylene or alkylidene group having 1 to 6 carbon atoms or an arylene or alkylarylene group having from 6 to 20 carbon atoms, Z means a cation, and n means an integer being two or higher.
    Type: Application
    Filed: October 6, 2009
    Publication date: August 11, 2011
    Applicant: CLARIANT FINANCE (BVI) LIMITED
    Inventors: Steve Heath, Gordon Moir, Marc Archibald, John Goulding
  • Publication number: 20110172194
    Abstract: This invention relates to a composition that comprises inositol phosphates and/or bisphosphonates, and to the use thereof to prevent the loss of substances of biological interest in the body of patients subjected to dialysis and to maintain sufficient physiological levels of said substances to regulate physiological and/or pathological processes, these substances being inhibitors of pathological crystallisation.
    Type: Application
    Filed: May 14, 2009
    Publication date: July 14, 2011
    Inventors: Félix Grases Freixedas, Joan Perello Bestard, Fernando Tur Espinosa, Antonia Costa Bauza, Rafael M. Prieto Almirall, Isabel Gomila Muñiz
  • Publication number: 20110008461
    Abstract: A PEPCK inhibitor can include identifying a molecule that has a size capable of fitting into and interacting with the PEPCK binding site and at least one of the following: (a) a first terminal substituent having co-planar atoms acting as metal ligands to the active site metal ion PEPCK; (b) at least one of an atom or substituent at positions 2 or 3 from the first terminal substituent includes a neutral carbon center or include an oxygen, sulfur, selenium, or other atom with similar physiochemical properties; (c) at least one of an atom or substituent at positions 2 or 3 from the first terminal substituent is devoid of an electropositive atom or substituents; or (d) a second terminal substituent opposite of the first terminal substituent, said second terminal substituent having an atom that is a hydrogen boding acceptor and/or is negatively charged.
    Type: Application
    Filed: July 12, 2010
    Publication date: January 13, 2011
    Inventors: Gerald Carlson, Todd Holyoak, Sarah Sullivan, Rose Mary Stiffin
  • Publication number: 20100240612
    Abstract: The invention provides methods to treat a mycobacterium infection and methods to inhibit mycobacterial polyprenyl pyrophosphate synthesis with a compound of formula I. The invention also provides novel compounds of formula I as well as salts and prodrugs thereof.
    Type: Application
    Filed: March 22, 2010
    Publication date: September 23, 2010
    Applicant: University of Iowa Research Foundation
    Inventors: David F. Wiemer, Rocky J. Barney, Raymond J. Hohl
  • Publication number: 20100197961
    Abstract: An adduct of 1-hydroxyethylidene-1,1-diphosphonic acid and from 0.5 to 10 moles of ethylenediamine disuccinic acid or a salt thereof per mole of 1-hydroxyethylidene-1,1-5 diphosphonic acid, wherein said adduct is in the form of a solid.
    Type: Application
    Filed: July 22, 2008
    Publication date: August 5, 2010
    Applicant: INNOSPEC LIMITED
    Inventor: Matthew Robert Giles
  • Publication number: 20100098632
    Abstract: This document provides methods and materials related to hydroxyapatite particles. For example, hydroxyapatite particles, methods for making hydroxyapatite particles, and methods for using hydroxyapatite particles are provided herein.
    Type: Application
    Filed: July 12, 2007
    Publication date: April 22, 2010
    Inventors: Stephen J. Russell, Kah-Whye Peng, Hooi Tin Ong
  • Patent number: 7560490
    Abstract: The present invention relates to a composition for prevention and/or treatment of metabolic diseases of bones comprising at least one bisphosphonate; viscosity agents comprising carboxymethylcellulose and xanthan gum; at least one flavoring agent; and purified water; a process for preparing a composition according to the present invention; and use of such a composition for prevention, treatment and/or diagnosis of metabolic diseases of bones, especially for children.
    Type: Grant
    Filed: January 23, 2001
    Date of Patent: July 14, 2009
    Assignees: GADOR S.A., University of Leiden
    Inventors: Daniel Zanetti, Damian Cairatti, Enrique Piccinni, Emilio J. A. Roldan, Socrates Papapoulos
  • Patent number: 7288673
    Abstract: A salt of substituted or unsubstituted methylene bisphosphonic acid of formula I wherein X1 and X2 are both chlorine or one of X1 and X2 is hydrogen and one is chlorine and the salt is selected from the group consisting of a C1-16 straight or branched primary, secondary or tertiary alkyl amine salt, an aralkyl amine salt, and a basic N-containing heterocycle salt. The salts are used for preparing pharmaceutically relevant compounds.
    Type: Grant
    Filed: December 1, 2003
    Date of Patent: October 30, 2007
    Assignee: AstraZeneca UK Limited
    Inventor: Mark Purdie
  • Patent number: 7109184
    Abstract: Disclosed is a phosphate transport inhibiting compound represented by Structural Formula (I): R1 and R2 are independently —H, an electron withdrawing group or a C1–C10 alkyl group. Y is a covalent bond, a substituted methylene group, an unsubstituted methylene group or —CR1R2P(O)(OH)—. R3 is a hydrocarbyl group optionally comprising one or more amine, ammonium, ether, thioether or phenylene linking groups, a substituted hydrocarbyl group optionally comprising one or more amine, ammonium, ether, thioether or phenylene linking groups, a heteroaryl group, a substituted heteroaryl group or a phenyl group substituted with one or more groups selected from —Cl, —Br, —F, —CN, —NO2, —ORa, —N(Ra)2, —COORa, —CON(Ra)2, —CORa, —S(O)Ra, —S(O)2Ra, —S(O)2N(Ra)2, —NRaS(O)2Ra, —NRaCORa, a halogenated lower alkyl group, an aryl group, a substituted aryl group, or a halogenated alkoxy group. Each Ra is independently —H, lower alkyl, substituted lower alkyl, aryl or substituted aryl.
    Type: Grant
    Filed: March 19, 2003
    Date of Patent: September 19, 2006
    Assignee: Genzyme Corporation
    Inventors: Thomas H. Jozefiak, Cecilia M. Bastos, Chad C. Huval
  • Patent number: 6909010
    Abstract: A facile synthesis of symmetric esters of C1-C10 alkylenebisphopsphonic acids is disclosed in which a C1-C10 alkylenebis(phosphonic dichloride) is reacted with an alcohol in the presence of a catalytic amount of 1H-tetrazole and a base in an aprotic solvent to form a first reaction mixture. The first reaction mixture is maintained for a time period sufficient to form a C1-C10 alkylenebis(chloro ester phosphonate) that is reacted under basic conditions with an excess of a hydroxylated compound to form a second reaction mixture that is itself maintained for a time period sufficient to form a C1-C10 alkylenebis(ester phosphonate) partial ester, homoleptic tetraester or mixed tetraester. The material so formed can be recovered or used as is.
    Type: Grant
    Filed: April 5, 2002
    Date of Patent: June 21, 2005
    Assignee: Loyola University of Chicago
    Inventors: Albert W. Herlinger, Dominique C. Stepinski
  • Publication number: 20040266735
    Abstract: The present invention relates to derivatives of 1-hydroxymethylene-1,1-bisphosphonic acid, the pharmaceutical compositions comprising them, and their application in therapeutics, particularly for the treatment of cancerous tumors. It is also directed to a methods of preparation of such derivatives.
    Type: Application
    Filed: July 12, 2004
    Publication date: December 30, 2004
    Applicant: Universite Paris 13
    Inventors: Marc Lecouvey, Yves Leroux, Michel Kraemer, Michel Crepin, Driss El Manouni, Malika Louriki
  • Publication number: 20040259846
    Abstract: A pharmaceutically acceptable alendronate salt in an amorphous form.
    Type: Application
    Filed: July 26, 2004
    Publication date: December 23, 2004
    Inventors: Yusuf Khwaja Hamied, Dharmaraj Ramachandra Rao, Rajendra Narayanrao Kankan
  • Publication number: 20040171870
    Abstract: A process for the preparation of salts of substituted or unsubstituted methylene bisphosphonic acids by hydrolysing the corresponding acid ester with hydrochloric acid, removing water from the acid azeotropically prior to addition of an amine or a base to produce the resultant salt in good yield.
    Type: Application
    Filed: December 1, 2003
    Publication date: September 2, 2004
    Applicant: AstraZeneca UK Limited, a London corporation
    Inventor: Mark Purdie
  • Patent number: 6743784
    Abstract: A method for treating symptoms, diseases and conditions in extra-reproductive tract tissues that are responsive to treatment with estrogen, using triarylethanes of formula (I) wherein R1 is —O(CH2)mR3 or —(CH2)nR3; wherein R3 is an anionic substituent; m is an integer from 1 to 4; and n is an integer from 0 to 4; and wherein R2 is either H or —OH. Each of R1 and R2 can be either meta or para to its respective phenyl ethyl linkage. Compounds having the formula (I) wherein R1 is —O(CH2)mR3 or —(CH2)nR3; R3 is an anionic substituent; m is 1, 2, 3 or 4; n is 0, 1, 2, 3 or 4; R2 is H or —OH; and wherein each of R1 and R2 is independently meta or para to its respective phenyl ethyl linkage are also provided, with the proviso that R2 is not para —OH when m is 1 and R3 is —COOH.
    Type: Grant
    Filed: October 15, 2001
    Date of Patent: June 1, 2004
    Assignee: The University of Georgia Research Foundation, Inc.
    Inventor: Peter C. Ruenitz
  • Publication number: 20040087554
    Abstract: The invention relates to a method of producing the 1-hydroxy-1,1-diphosphonic acid compounds of general formula (I), and/or the pharmacologically acceptable salts thereof, in which formula R1 represents hydrogen, OH, NO2, Cl, F, Br, C1-C6 alkyl that may be substituted with halogen, amine and/or aminoalkyl, C1-6 alkoxy, aryl, heteroaryl, a group NR3R4, wherein R3 and R4 may be the same or different and represent hydrogen, C1-C6 alkyl, halogen-substituted alkyl, hydroxy-C1-alkyl; R2 represents hydrogen, halogen, amine that may be substituted, C1-C6 alkyl that may be substituted with halogen, amine and/or aminoalkyl, C1-C6 alkoxy, aryl, heteroaryl; Y represents O, S or NH; Z represents C1-C5 alkylene that may be substituted with amine groups, and m and n are 0 or 1, with the proviso that if n=1, m=1.
    Type: Application
    Filed: September 15, 2003
    Publication date: May 6, 2004
    Inventors: Helmut Blum, Wolfgang Greb, Yurii Pustovit, Gerd-Volker Roschenthaler
  • Publication number: 20040043967
    Abstract: Provided is a novel method of making bisphosphonic acids, e.g. risedronic acid, including the step of combining a carboxylic acid, phoshorous acid, and a halophosphorous compound in the presence of a diluent that is an aromatic hydrocarbon or a silicone fluid. When the diluent is an aromatic hydrocarbon, a inert support or ortho-phosphoric acid codiluent is advantageously included.
    Type: Application
    Filed: May 19, 2003
    Publication date: March 4, 2004
    Inventors: Rami Lidor-Hadas, Zvi Harel, Revital Lifshitz-Liron, Eti Kovalevski-Ishai
  • Patent number: 6657076
    Abstract: A process for the preparation of salts of substituted or unsubstituted methylene bisphosphonic acids by hydrolysing the corresponding acid ester with hydrochloric acid, removing water from the acid azeotropically prior to addition of an amine or a base to produce the resultant salt in good yield.
    Type: Grant
    Filed: March 14, 2002
    Date of Patent: December 2, 2003
    Assignee: AstraZeneca UK Limited
    Inventor: Mark Purdie
  • Publication number: 20020042539
    Abstract: The present invention provides a pharmaceutical compound, or pharmaceutically acceptable salt thereof, for use in medicine, wherein said compound is of formula I 1
    Type: Application
    Filed: July 9, 2001
    Publication date: April 11, 2002
    Inventors: Erik Arstad, Lars Skattebol
  • Patent number: 6323190
    Abstract: A method for treating symptoms, diseases and conditions in extra-reproductive tract tissues that are responsive to treatment with estrogen, using triarylethanes of formula (I) wherein R1 is —O(CH2)mR3 or —(CH2)nR3; wherein R3 is an anionic substituent; m is an integer from 1 to 4; and n is an integer from 0 to 4; and wherein R2 is either H or —OH. Each of R1 and R2 can be either meta or para to its respective phenyl ethyl linkage. Compounds having the formula (I) wherein R1 is —O(CH2)mR3 or —(CH2)nR3; R3 is an anionic substituent; m is 1, 2, 3 or 4; n is 0, 1, 2, 3 or 4; R2 is H or —OH; and wherein each of R1 and R2 is independently meta or para to its respective phenyl ethyl linkage are also provided, with the proviso that R2 is not para —OH when m is 1 and R3 is —COOH.
    Type: Grant
    Filed: July 28, 1999
    Date of Patent: November 27, 2001
    Assignee: The Univeristy of Georgia Research Foundation, Inc.
    Inventor: Peter C. Ruenitz
  • Patent number: 6242433
    Abstract: The present invention relates to novel geranylgeranyl derivatives and the pharmaceutically acceptable salts thereof having antiproliferative activity in eukaryotic cells with respect to the inhibition of protein geranygeranylation. The invention also relates to the pharmaceutical compositions containing the novel derivatives and to the process of preparation thereof.
    Type: Grant
    Filed: September 15, 1998
    Date of Patent: June 5, 2001
    Assignee: Laboratori Baldacci SpA
    Inventors: Aldo Balsamo, Bruno Macchia, Marco Macchia, Massimo Baldacci, Romano Danesi, Mario Del Tacca
  • Patent number: 6121253
    Abstract: This invention relates to prostaglandin-bisphosphonate conjugates. These conjugates are effective for treating or preventing bone diseases such as osteoporosis. These conjugates simultaneously deliver a prostaglandin agent for increasing bone formation and a bisphosphonate agent for inhibiting bone resorption.
    Type: Grant
    Filed: November 15, 1999
    Date of Patent: September 19, 2000
    Assignee: Merck Frosst Canada & Co.
    Inventors: Yongxin Han, Robert N. Young, Laurent Gil, Rejean Ruel
  • Patent number: 5824661
    Abstract: Compounds of the formula ##STR1## where m and n are integers 0 to 10 and m+n equals 0 to 10, (a) X is O or S(b) Z is a covalent bond; a monocyclic or polycyclic carbocycle ring moiety; or a monocyclic or polycyclic heterocyclic ring moiety containing one or more heteroatoms selected from O, S, or N;(c) Q is covalent bond; O; or S;(d) R is COOH, SO.sub.3 H, PO.sub.3 H.sub.2, or P(O)(OH)R.sup.4, wherein R.sup.4 is C.sub.1 -C.sub.8 alkyl;(e) R.sup.1, R.sup.2 and R.sup.5 are as defined in the claims.are useful in the treatment of calcium and phosphate elated disorders, such as arthritis and the like.
    Type: Grant
    Filed: September 7, 1994
    Date of Patent: October 20, 1998
    Assignee: The Procter & Gamble Company
    Inventors: Marion David Francis, Susan Mary Kaas, Frank Hallock Ebetino
  • Patent number: 5783728
    Abstract: An improved method is disclosed for the preparation of novel alkali metal diphosphinate salts by the reaction of an acetylenic compound with an alkali metal hypophosphite in the presence of a free radical source, the use of these novel compounds in further reactions to prepare diphosphonate compounds and diphosphinate containing adducts, oligomers and polymers and utilization of these compounds, polymers and oligomers to control calcium carbonate scale and mild steel corrosion in cooling water.
    Type: Grant
    Filed: January 7, 1997
    Date of Patent: July 21, 1998
    Assignee: Nalco Chemical Company
    Inventors: James F. Kneller, Donald A. Johnson, Vytas Narutis, Binaifer S. Khambatta
  • Patent number: 5772893
    Abstract: The invention is a method for the prevention of scale formation on metal or other surfaces in contact with scale-forming industrial water with an effective scale-inhibiting amount of an ether 1,1-diphosphonate of the general formula: ##STR1## The invention is also a method for the prevention of corrosion on metal surfaces in contact with corrosive industrial water with an effective corrosion-inhibiting amount of an ether 1,1-diphosphonate of the same general formula. A preferred ether 1, 1-diphosphonate is 1,1, diphosphono-4,7-dioxaoctane for both methods.
    Type: Grant
    Filed: August 13, 1996
    Date of Patent: June 30, 1998
    Assignee: NALCO Chemical Company
    Inventors: Peter E. Reed, Michael A. Kamrath, Phillip W. Carter, Ronald V. Davis
  • Patent number: 5753634
    Abstract: Disclosed are quaternary nitrogen-containing, saturated or unsaturated monocyclic and bicyclic ring-containing bisphosphonate compounds, and pharmaceutically-acceptable salts and esters thereof. These compounds, which are useful for treating or preventing disorders of calcium and phosphate metabolism, have the following general structure: ##STR1## wherein (a) each X and Y are independently selected from nil, O, S, NR.sup.1 and N.sup.+ (R.sup.2).sub.2 ; if no R.sup.1 is N.sup.+ (R.sup.2).sub.2, then at least one of X or Y must be N.sup.+ (R.sup.2).sub.2 ;(b) m and n and m+n are integers from 0 to 5; p and q and p+q are integers from 0 to 3;(c) s is an integer from 0 to 2 and when m+n=0 and X is nil, s=2;(d) each R.sup.1 is independently selected from the group consisting of nil, N.sup.+ (R.sup.2).sub.2, R.sup.9 SR.sup.6, SR.sup.6, hydrogen, hydroxy; unsubstituted or substituted C.sub.1 -C.sub.8 alkyl, --OR.sup.3, --CO.sub.2 R.sup.3, --O.sub.2 CR.sup.3, NR.sup.3.sub.2, --N(R.sup.3)C(O)R.sup.3, --C(O)N(R.sup.3).
    Type: Grant
    Filed: April 30, 1993
    Date of Patent: May 19, 1998
    Assignee: The Procter & Gamble Company
    Inventors: Frank Hallock Ebetino, Marion David Francis, Susan Mary Kaas
  • Patent number: 5712396
    Abstract: .alpha.-Phosphonosulfonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula ##STR1## wherein R.sup.2 is OR.sup.5 or R.sup.5a ; R.sup.3 and R.sup.5 are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R.sup.5a is H, alkyl, arylalkyl or aryl; R4 is H, alkyl, aryl, arylalkyl, or cycloalkyl;, Z is H, halogen, lower alkyl or lower alkenyl; and R.sup.1 is a lipophilic group which contains at least 7 carbons and is alkyl, alkenyl, alkynyl, mixed alkenyl-alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl; as further defined above; including pharmaceutically acceptable salts and or prodrug esters of the phosphonic (phosphinic) and/or sulfonic acids.
    Type: Grant
    Filed: July 5, 1994
    Date of Patent: January 27, 1998
    Inventors: David R. Magnin, Scott A. Biller, John K. Dickson, Jr., R. Michael Lawrence, Richard B. Sulsky
  • Patent number: 5618804
    Abstract: A methane diphosphonic acid derivative represented by the general formula (I): ##STR1## wherein, X and Y are defined in the specification; m represents an integer of 0 to 3; n represents an integer of 0 to 4; and each X of the (X).sub.m and each Y of the (Y).sub.n may be either identical or different; . . . represents a double bond or single bond; A is --(CH.sub.2)a--(D)b--(CH.sub.2)c-- (wherein D is sulfur, oxygen, NH, alkyl-substituted N, or CH.sub.2, a and c are integers of 0 to 10 and b is 0 or 1), or --(CH.dbd.CH)d.dbd.CH= (wherein d is an integer of 0 to 2, and B does not exist when A represents --CH.dbd.CH)d--CH.dbd.), B refers to a hydrogen atom, alkyl group, amino group, monoalkylamino group, dialkylamino group, acylamino group, hydroxyl group, alkoxy group, trialkylsiloxy group or acyloxy group, and each of R.sup.1, R.sup.2, R.sup.3 and R.sup.
    Type: Grant
    Filed: January 14, 1994
    Date of Patent: April 8, 1997
    Assignee: Toray Industries, Inc.
    Inventors: Norio Kawabe, Hiromi Uchiro, Teruo Nakadate, Masahiko Tanahashi, Yuriko Funaba
  • Patent number: 5574025
    Abstract: The compounds disclosed inhibit the prenylation of several proteins. These compounds are potent inhibitors of famesyl-protein transferase and geranylgeranyl-protein transferase. Further contained in this invention are chemotherapeutic compositions containing these prenyl-transferase inhibitors and methods for their production.
    Type: Grant
    Filed: October 26, 1994
    Date of Patent: November 12, 1996
    Assignee: Merck & Co., Inc.
    Inventors: Neville J. Anthony, Robert P. Gomez, Charles A. Omer
  • Patent number: 5504237
    Abstract: PIA.sub.2 inhibitors selected from the group consisting of ##STR1## wherein A is selected from the group consisting of ##STR2## and Z, W, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, X, X' and Y are as defined herein.
    Type: Grant
    Filed: April 27, 1995
    Date of Patent: April 2, 1996
    Assignee: Monsanto Company
    Inventor: Patrick J. Lennon
  • Patent number: 5428181
    Abstract: A compound represented by the general formula: ##STR1## wherein A-O-denotes a residue of a compound having an estrogenic activity; R.sub.1 denotes H or a C.sub.1 -C.sub.6 alkyl group; X denotes a single bond, a C.sub.1 -C.sub.10 alkylene group or a group of the formula ##STR2## wherein R.sub.2 denotes H or a C.sub.1 -C.sub.5 alkyl group; Z denotes a nitro group or a halogen; n is an integer of 3 to 12; k is an integer of 1 to 5; L is an integer of 0 to 5; and q is an integer of 1 to 3,and physiologically acceptable salts thereof are disclosed.The compounds have a high affinity to bone tissues, and the compounds per se and metabolites thereof show significant therapeutic effect on bone diseases such as osteoporosis, rheumatoid arthritis and osteoarthritis.
    Type: Grant
    Filed: December 24, 1992
    Date of Patent: June 27, 1995
    Assignee: Hoechst Japan Limited
    Inventors: Tatsuo Sugioka, Mizuho Inazu
  • Patent number: 5405994
    Abstract: The present invention relates to disodium 4-chlorophenylmethylenebisphosphonate monohydrate. The invention also relates to a method of preparing this form of the monohydrate, as well as to pharmaceutical compositions in which disodium tiludronate monohydrate is present as the active principle.
    Type: Grant
    Filed: August 4, 1993
    Date of Patent: April 11, 1995
    Assignee: Sanofi
    Inventors: Michel Bonnery, Michel Bouisset, Raphael Sole
  • Patent number: 5374628
    Abstract: Phosphonic acid squalene synthetase inhibitors are provided which are effective in lowering serum cholesterol and have the formula ##STR1## wherein m is 0 to 3, n is 1 to 5, Y.sup.1 and Y.sup.2 are H or halogen, R.sup.2, R.sup.3 and R.sup.4 are H, metal ion, C.sub.1 to C.sub.8 alkyl, C.sub.3 to C.sub.12 alkenyl, or prodrug ester, and R.sup.1 is a substituted or unsubstituted heteroaryl group or a substituted phenyl group.
    Type: Grant
    Filed: October 18, 1993
    Date of Patent: December 20, 1994
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Scott A. Biller
  • Patent number: 5364846
    Abstract: Substituted aminoethane-1,1-bisphosphonic acids and aminoethane-1,1-alkylphosphinophosphonic acids, processes for their preparation and use thereofThe invention relates to compounds of the formula I ##STR1## in which R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are a hydrogen atom or (C.sub.5 -C.sub.5)-alkyl, m is the integer 0 or 1, x is (C.sub.1 -C.sub.10)-alkyl, mono- or polysubstituted, a 5- or 6-membered ring having one nitrogen atom and optionally a further nitrogen or oxygen atom; aryl having 6 or 10 carbon atoms, which can be substituted; or cycloalkyl, to processes for the preparation of the compound of the formula I; to pharmaceuticals, and to their use for the treatment of osteoporosis and degenerative joint diseases.
    Type: Grant
    Filed: November 24, 1993
    Date of Patent: November 15, 1994
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Hans Lang, Christoph Naumann, Ruth Raiss, Osamu Komiyama, Yoshiko Terui
  • Patent number: 5278153
    Abstract: Phosphonic acid squalene synthetase inhibitors are provided which are effective in lowering serum cholesterol and have the formula ##STR1## wherein m is 0 to 3, n is 1 to 5, Y.sup.1 and Y.sup.2 are H or halogen, R.sup.2, R.sup.3 and R.sup.4 are H, metal ion, C.sub.1 to C.sub.8 alkyl, C.sub.3 to C.sub.12 alkenyl, or prodrug ester, and R.sup.1 is a substituted or unsubstituted heteroaryl group or a substituted phenyl group.
    Type: Grant
    Filed: May 18, 1992
    Date of Patent: January 11, 1994
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Scott A. Biller
  • Patent number: 5254544
    Abstract: Hydroxyphosphinyl phosphonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula ##STR1## wherein R.sup.2, R.sup.3 and R.sup.4 are independently H, alkyl, metal ion or a prodrug ester; and R.sup.1 is a lipophilic group which contains at least 6 carbons and is alkyl, alkenyl, alkynyl, mixed alkenylalkynyl, a hetero-containing moiety as defined herein, or a phenylalkyl or phenylalkenyl group including those containing a biphenyl group.
    Type: Grant
    Filed: September 25, 1992
    Date of Patent: October 19, 1993
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Scott A. Biller, John K. Dickson, Jr.
  • Patent number: 5212164
    Abstract: Compounds which are inhibitors of cholesterol biosynthesis (by inhibiting de novo squalene biosynthesis), and thus are useful as hypocholesterolemic agents and antiatherosclerotic agents are provided which have the structure ##STR1## wherein m is 0, 1, 2 or 3; n is 0, 1, 2, 3 or 4;Y.sup.1 and Y.sup.2 are H or halogen;R.sup.2, R.sup.3 and R.sup.4 may be the same or different and are independently H, metal ion, C.sub.1 to C.sub.8 alkyl or C.sub.3 to C.sub.12 alkenyl;X is O, S, NH or NCH.sub.2 R.sup.15 wherein R.sup.15 is H or C.sub.1 to C.sub.5 alkyl; andR.sup.1 is R.sup.5 --Q.sup.1 --Q.sup.2 --Q.sup.3 -- wherein R.sup.5, Q.sup.1, Q.sup.2 and Q.sup.3 are as defined herein;and when m is o, X is other than S; and if m is o and X is 0, then n is 1, 2, 3 or 4; including all stereoisomers thereof.
    Type: Grant
    Filed: March 29, 1990
    Date of Patent: May 18, 1993
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Scott A. Biller, Michael J. Sofia