Nitrogen, Other Than As Nitro Or Nitroso, Attached Directly Or Indirectly To The Acridine Ring System By Nonionic Bonding Patents (Class 546/104)
  • Patent number: 6296787
    Abstract: Novel heterocyclic compounds which generate chemiluminescence on reaction with a phosphatase enzyme are provided as well as a process for their preparation and intermediates useful therein. The compounds comprise a nitrogen, oxygen or sulfur-containing heterocyclic ring system bearing an exocyclic carbon—carbon double bond. The double bond is further substituted at the distal carbon with a phosphate group and an oxygen or sulfur atom-containing group. Novel compositions further comprising a cationic aromatic compound (CAC) in addition to the heterocyclic phosphate compound are provided. The addition of the CAC in the composition greatly increases the production of chemiluminescence and provides improved detection sensitivity. Compositions further comprising an anionic surfactant and a non-ionic surfactant provide additional improvements in detection sensitivity.
    Type: Grant
    Filed: April 26, 2000
    Date of Patent: October 2, 2001
    Assignee: Lumigen, Inc.
    Inventors: Hashem Akhavan-Tafti, Zahra Arghavani, Renuka DeSilva
  • Patent number: 6274768
    Abstract: This invention relates to intermediates in the preparation of acridin derivatives of general formula or pharmaceutically acceptable salts thereof, and to a method of producing them.
    Type: Grant
    Filed: March 30, 2000
    Date of Patent: August 14, 2001
    Assignee: Gruenenthal GmbH
    Inventors: Claudia Katharina Puetz, Wolfgang Werner Alfred Strassburger, Oswald Zimmer, Werner Guenter Englberger
  • Patent number: 6248884
    Abstract: Extended rhodamine compounds exhibiting favorable fluorescence characteristics having the structure are disclosed. In addition, novel intermediates for synthesis of these dyes are disclosed, such intermediates having the structure In addition, methods of making and using the dyes as fluorescent labels are disclosed.
    Type: Grant
    Filed: June 3, 1999
    Date of Patent: June 19, 2001
    Assignee: The Perkin-Elmer Corporation
    Inventors: Joe Y. L. Lam, Scott C. Benson, Steven M. Menchen
  • Patent number: 6214816
    Abstract: The compounds are N-substituted azaheterocyclic compounds of formula I wherein R1 and R2 independently are hydrogen, halogen, trifluoromethyl, hydroxy, C1-6-alkyl or C1-6-alkoxy; and Y is >N—CH2— wherein only the underscored atom participates in the ring system; and X is —C(R6R7)—, —CH2CH2—, —CH═CH—CH2—, —CH2—CH═CH—, —CH2—(C═O)—, —(C═O)—CH2—, —CH2CH2CH2—, —CH═CH—, CH(R10)CH2—, —CH2CH(R10) or —(C═O)— wherein R6 and R7 independently are hydrogen or C1-6-alkyl and wherein R10 is C1-6-alkyl or phenyl; and r is 0, 1 or 2; and Z is selected from wherein A is —CH2—, —O—, —S— or —N(R5)— wherein R5 is H or C1-6-alkyl; and R3 is —(CH2)pCOR4 wherein p is 1, 2, 3 or 4 and R4 is OH, NH2, NHOH or C1-6-alkoxy; or a pharmaceutically acceptable salt th
    Type: Grant
    Filed: March 10, 1999
    Date of Patent: April 10, 2001
    Assignee: Novo Nordisk A/S
    Inventors: Rolf Hohlweg, Tine Krogh Jørgensen, Knud Erik Andersen, Uffe Bang Olsen, Zdenék Polivka, Karel Sindelar
  • Patent number: 6197825
    Abstract: The present invention relates to chromotropic nitrone spin trapping agents, methods of making these agents, compositions comprising same, and methods of their use. In particular, azulenyl nitrones of the present invention are effective agents for trapping free radical species and find use as efficient antioxidants in physicochemical and biological systems. Accordingly, the invention also relates to spin adducts formed from the combination of azulenyl nitrones with free radicals. The compounds of the present invention are readily prepared from available starting materials and find further use in assays and in a number of diagnostic, prophylactic and therapeutic applications, including but not limited to the alleviation, modulation and inhibition of the negative effects of carbon-centered or oxygen-centered radical species and other products of oxidation. Moreover, the combination adducts may be calorimetrically detected and, optionally, isolated and characterized to obtain valuable information (e.g.
    Type: Grant
    Filed: May 28, 1998
    Date of Patent: March 6, 2001
    Assignee: Florida International University
    Inventor: David Alan Becker
  • Patent number: 6172058
    Abstract: A pharmaceutical compound of the formula in which R1 is C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-10 alkyl, C3-10 cycloalkyl-C2-10 alkenyl, C3-10 cycloalky-C2-10 alkynyl, optionally substituted phenyl-C1-10 alkyl, optionally substituted phenyl-C2-10 alkenyl, optionally substituted phenyl-C2-10 alkynyl, optionally substituted naphthyl, optionally substituted naphthyl-C1-10 alkyl, C1-10 alkoxy-C1-10 alkyl, C3-10 cycloalkoxy-C1-10 alkyl, optionally substituted heterocyclyl, optionally substituted heterocyclyl-C1-10 alkyl, optionally substituted phenyl fused to C5-10 cycloalkyl, optionally substituted tricyclic, optionally substituted tricyclic-C1-10 alkyl, or [optionally substituted phenyl(CH2)n]2-C1-10 alkyl, where n is 0 or 1 to 4, and R2 is hydrogen or one of the values for R1; or a salt or ester thereof.
    Type: Grant
    Filed: April 3, 1998
    Date of Patent: January 9, 2001
    Assignee: Lilly, SA
    Inventors: Concepci{acute over (o)}n Pedregal Tercero, Ivan Collado Cano, Angel Maz{acute over (o)}n Ruiz
  • Patent number: 6171520
    Abstract: Disclosed are SH-labeling reagents containing acridine compounds represented by the following formula (I): wherein A represents the following group: —(CH2)m1— or —(CH2)m2—Q—(CH2)n— in which Q represents a group —S+RX−—, a group —N+RR1X−— wherein R1 represents an alkyl group having 1 to 6 carbon atoms or an aryl group, a group wherein R2 and R3 may be the same or different and are each independently a group —(CH2)k— (k: a number of 1 to 3) or —O(CH2CH2O)l— (l: a number of 1 to 3), m1 stands for a number of 1 to 6, m2 denotes a number of 0 to 2, n means a number of 1 to 2; R represents an alkyl group having 1 to 6 carbon atoms or an aryl group; and X− represents an anion, or intermediates thereof; preparation processes of the acridine compounds; and methods for labeling analytes by using the compounds.
    Type: Grant
    Filed: November 14, 1997
    Date of Patent: January 9, 2001
    Assignee: SS Pharmaceutical Co., Ltd.
    Inventors: Kazuhiro Imai, Hiromichi Eto, Takeshi Kotsugai, Tadashi Narita
  • Patent number: 6162610
    Abstract: Xanthan esters and acridans are substrates for horseradish peroxidase. These stable, enzymatically cleavable chemiluminescent esters are substrates for horseradish peroxidase which, together with peroxide is among the extensively used enzyme in enzyme-linked detection methods, including immunoassays, oligonucleotide detection and nucleic acid hybridization. The novel compounds are used, together with peroxide, alkali and the peroxidase, to indicate the presence and/or concentration of target compounds. The assays may be enhanced by the use of polymeric quaternary onium enhancement compounds or similar compounds selected to enhance the chemiluminescence emitted.
    Type: Grant
    Filed: September 11, 1998
    Date of Patent: December 19, 2000
  • Patent number: 6162918
    Abstract: The invention relates to new and known tricyclic dione derivatives of the general formula ##STR1## and to their salts which are inhibitors of herpes simplex virus thymidine kinase in the treatment and prophylaxis of infections caused by herpes simplex virus.
    Type: Grant
    Filed: June 28, 1999
    Date of Patent: December 19, 2000
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Joseph Armstrong Martin, Bradley Stuart Sherborne, Gareth Mark Taylor
  • Patent number: 6130228
    Abstract: Compounds of Formula (I), methods for their preparation, pharmaceutical formulations and use thereof.
    Type: Grant
    Filed: August 25, 1998
    Date of Patent: October 10, 2000
    Assignee: University of Strathclyde
    Inventors: George Rennet Proctor, Alan Lang Harvey, Maureen Theresa McKenna, Steven John Mullins
  • Patent number: 6126870
    Abstract: Chemiluminescent labeling compounds and chemiluminescent labeled conjugates are provided. The compounds comprise an acridan ring bearing an exocyclic double bond and further contain a labeling substituent which permits attachement to compounds of interest. The novel chemiluminescent compounds and labeled conjugates generated chemiluminescence rapidly after undergoing a reaction with an acid, an oxidant and a base. The compounds and conjugates are useful in assays of an analyte in a sample and in assays employing labeled specific binding pairs.
    Type: Grant
    Filed: June 17, 1998
    Date of Patent: October 3, 2000
    Assignee: Lumigen, Inc.
    Inventor: Hashem Akhavan-Tafti
  • Patent number: 6114332
    Abstract: A compound which is a bis(acridinecarboxamide) or bis(phenazinecarboxamide) derivative of formula (I): ##STR1## wherein each X, which may be the same or different in a given molecule, is --CH.dbd. or --N.dbd. each of R.sub.1 to R.sub.4 which may be the same or different, H, C.sub.1 -C.sub.4 alkyl, OH, SH, NH.sub.2, C.sub.1 -C.sub.4 alkoxy, aryloxy, NHR, N(R).sub.2, SR, SO.sub.2 R wherein R is C.sub.1 -C.sub.4 alkyl, CF.sub.3, NO.sub.2 or halogen, or R.sub.1 and R.sub.2 together form a methylenedioxy group; each of R.sub.5 and R.sub.6, which may be the same or different, is H or C.sub.1 -C.sub.4 alkyl; Z is (CH.sub.2).sub.n, (CH.sub.2).sub.n O(CH.sub.2).sub.n, (CH.sub.2).sub.n N(R.sub.7)(CH.sub.2).sub.n, (CH.sub.2).sub.n N(R.sub.7)(CH.sub.2).sub.m N(R.sub.7)(CH.sub.2).sub.n or (CH.sub.2).sub.n N(CH.sub.2 CH.sub.2).sub.2 N(CH.sub.2).sub.n wherein R.sub.7 is H or C.sub.1 -C.sub.
    Type: Grant
    Filed: June 18, 1999
    Date of Patent: September 5, 2000
    Assignee: Xenova Limited
    Inventors: William Alexander Denny, Swarnalatha Akuritaya Gamage, Julie Ann Spicer, Bruce Charles Baguley, Graeme John Finlay
  • Patent number: 6111109
    Abstract: A process for producing an acridine carboxamide of formula (I): ##STR1## wherein each of R.sup.1, R.sup.2, R.sup.5 and R.sup.6, which may be the same or different, is H or an organic subsituent, x is from 1 to 6 and Y is N(R)2 wherein R is C.sub.1 -C.sub.6 alkyl, or a pharmaceutically acceptable salt thereof.
    Type: Grant
    Filed: June 18, 1999
    Date of Patent: August 29, 2000
    Assignee: Xenova Limited
    Inventors: William Alexander Denny, Swarnalatha Akuratiya Gamage, Julie Ann Spicer, Michael Wright, David Frank Hayman
  • Patent number: 6087502
    Abstract: Acridinium compounds and their conjugates exhibiting high chemiluminescence yield are provided. Such compounds may be used to enable a highly sensitive specific binding assay. The acridinium compounds are represented by formula (I): ##STR1## wherein A is a linker; Z is a binding group; Y is a counter ion; R.sup.1 and R.sup.2 are independently a substituent; p and m are independently an integer of from 0 to 4; n is an integer of from 2 to 5; and X is an organic intervening moiety with a functionality of at least n, having an aryloxy group or an arylsulfonamide group through which X binds to carbonyl carbon bonded to 9-position of the acridinium ring.
    Type: Grant
    Filed: July 31, 1996
    Date of Patent: July 11, 2000
    Assignee: Mochida Pharmaceuticals Co., Ltd.
    Inventor: Naofumi Sato
  • Patent number: 6083988
    Abstract: The present invention relates to chromotropic nitrone spin trapping agents, methods of making these agents, compositions comprising same, and methods of their use. In particular, azulenyl nitrones of the present invention are effective agents for trapping free radical species and find use as efficient antioxidants in physicochemical and biological systems. Accordingly, the invention also relates to spin adducts formed from the combination of azulenyl nitrones with free radicals. The compounds of the present invention are readily prepared from available starting materials and find further use in assays and in a number of diagnostic, prophylactic and therapeutic applications, including but not limited to the alleviation, modulation and inhibition of the negative effects of carbon-centered or oxygen-centered radical species and other products of oxidation. Moreover, the combination adducts may be calorimetrically detected and, optionally, isolated and characterized to obtain valuable information (e.g.
    Type: Grant
    Filed: September 4, 1997
    Date of Patent: July 4, 2000
    Inventor: David Alan Becker
  • Patent number: 6077845
    Abstract: This invention relates to acridin derivatives of general formula ##STR1## or pharmaceutically acceptable salts thereof, to a method of producing them and to their use as analgesics.
    Type: Grant
    Filed: June 29, 1999
    Date of Patent: June 20, 2000
    Assignee: Gruenenthal GmbH
    Inventors: Claudia Katharina Puetz, Wolfgang Werner Alfred Strassburger, Oswald Zimmer, Werner Guenter Englberger
  • Patent number: 6071908
    Abstract: A method of treating neoplastic disease wherein a patient in need of such treatment is administered an effective amount of a radiation-activated cytotoxin prodrug (RACP) which has low toxicity, which is reducible by reducing agents generated by the radiolysis of water and which, upon reduction, releases a sufficient amount of a cytotoxic effector of sufficient cytotoxic potency to kill tumor cells. The tumor cells are irradiated with ionizing radiation to reduce the prodrug which is present at the locus of the tumor cells to release the cytotoxic effector.
    Type: Grant
    Filed: May 7, 1998
    Date of Patent: June 6, 2000
    Assignee: Auckland Uniservices Limited
    Inventors: William A. Denny, Moena Tercel, William R. Wilson
  • Patent number: 6045727
    Abstract: Novel heterocyclic compounds which generate chemiluminescence on reaction with a phosphatase enzyme are provided as well as a process for their preparation and intermediates useful therein. The compounds comprise a nitrogen, oxygen or sulfur-containing heterocyclicring system bearing an exocyclic carbon-carbon double bond. The double bond is further substituted at the distal carbon with a phosphate group and an oxygen or sulfur atom-containing group. Novel compositions further comprising a cationic aromatic compound (CAC) in addition to the heterocyclic phosphate compound are provided. The addition of the CAC in the composition greatly increases the production of chemiluminescence and provides improved detection sensitivity. Compositions further comprising an anionic surfactant and a non-ionic surfactant provide additional improvements in detection sensitivity.
    Type: Grant
    Filed: August 13, 1997
    Date of Patent: April 4, 2000
    Assignee: Lumigen, Inc.
    Inventors: Hashem Akhavan-Tafti, Zahra Arghavani, Renuka DeSilva
  • Patent number: 6037347
    Abstract: The invention relates to a composition which is a pharmaceutical combination preparation comprising a compound which has an acetylcholinesterase-inhibitory action or exhibits muscarinergic action and a compound which increases the endogenous extracellular adenosine level, wherein the combination preparation is suitable for the treatment of dementia. The invention further relates to a process for the production of the combination preparation. The invention additionally relates to a process for treating patients in need of suitable therapy with the combination preparation.
    Type: Grant
    Filed: February 25, 1998
    Date of Patent: March 14, 2000
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Hans-Peter Schubert, Hildegard Nimmesgern, Karl Rudolphi
  • Patent number: 6020131
    Abstract: The present invention has an object to provide an easy method for detecting a nucleic acid polymer in aqueous phase.The present invention provides a method for detecting the amount of nucleic acid polymer, which comprises the steps of modifying an intercalator to be amphiphilic by using a hydrophobic group, spreading the amphiphilic intercalator on an aqueous solution containing a nucleic acid polymer to form a monolayer of said nucleic acid polymer and said amphiphilic intercalator at the gas-water interface, and measuring surface pressures per unit area of said monolayer.
    Type: Grant
    Filed: November 7, 1997
    Date of Patent: February 1, 2000
    Assignee: Research Development Corporation of Japan
    Inventors: Kunihara Ijiro, Masatsugu Shimomura
  • Patent number: 6018047
    Abstract: New acridinium compounds are provided which comply with formula 1, whereinA is a divalent organic moiety, such as an alkylene chain,X is a group which can be transformed together with C-9 of the acridine into a dioxetane by reaction with hydrogen peroxide, such as an aryloxy group,Y is a counter ion, andZ is a functional group, such as a carboxyl derivative.These acridinium compounds are useful as chemiluminogenic labels for both heterogeneous and homogeneous immunoassays.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: January 25, 2000
    Inventors: Gijsbert Zomer, Johannus Franciscus Cornelius Stavenuiter
  • Patent number: 6002007
    Abstract: Chemiluminescent acridinium derivatives of the formula I ##STR1## in which R.sup.4 represents a radical of the formula II or III ##STR2## and A.sup..theta., X--, R.sup.1 -R.sup.3, R.sup.5 and R.sup.6 have the stated meanings, as well as processes for the preparation of the compounds of the formula (I) and the use thereof in chemiluminescence immunoassays.
    Type: Grant
    Filed: July 20, 1993
    Date of Patent: December 14, 1999
    Assignee: Dade Behring Marburg GmbH
    Inventors: Tonio Kinkel, Peter Molz, Erwin Schmidt, Gerd Schnorr, Heinz Jurgen Skrzipczyk
  • Patent number: 5969139
    Abstract: The invention relates to new and known tricyclic dione derivatives of the general formula ##STR1## wherein W represents hydrogen or lower alkyl;X represents lower alkyl;Y represents NR1;R.sup.1 represents hydrogen, lower alkyl, lower alkoxycarbonyl or lower alkoxycarbonyl-lower alkyl;Z represents aryl or heteroaryl optionally substituted by one or more halo, cyano, nitro, lower alkyl, halo-lower alkyl, lower alkoxy, halo-lower alkoxy, COR.sup.2, OCOR.sup.2, CO.sub.2 R.sup.2, OR.sup.2, S(O).sub.n R.sup.2, NR.sup.2 R.sup.3, N(R.sup.4)COR.sup.5, Ar, Ar-lower alkyl, Het or Het-lower alkyl substituents and/or on adjacent carbon atoms by lower alkylenedioxy;R.sup.2, R.sup.3, R.sup.4 and R.sup.5 each individually represent hydrogen, lower alkyl, Ar, Ar-lower alkyl, Het or Het-lower alkyl substituents; or R.sup.2 and R.sup.3 together represent the group --CH.dbd.CH--CH.dbd.CH-- or --CH.dbd.N--CH.dbd.
    Type: Grant
    Filed: August 6, 1997
    Date of Patent: October 19, 1999
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Joseph Armstrong Martin, Bradley Stuart Sherborne, Gareth Mark Taylor
  • Patent number: 5891886
    Abstract: A new treatment schedule for administration of N-?2-(dimethylamino)ethyl!acridine-4-carboxamide and other related carboxamide anticancer drugs in which the drug is administered in a divided-dose schedule comprising two or more administrations at frequent intervals, for example every hour. Schedules to produce cyclic peaks/troughs in plasma levels are mentioned. The compounds can be used for circumventing multidrug resistance in cancers and may, for example, be used in combination with other cytotoxic drugs, especially non-topo II inhibitors. Treatment of melanoma and advanced colon cancer is included.
    Type: Grant
    Filed: August 29, 1997
    Date of Patent: April 6, 1999
    Assignee: Xenova Limited
    Inventors: Bruce Charles Baguley, Graham John Atwell, William Alexander Denny, Graeme John Finlay, Gordon William Rewcastle
  • Patent number: 5892042
    Abstract: An acridine derivative metal complex of formula 2 having a large absorption in the near-infrared range and a reduced absorption in the visible range, which acridine derivative metal complex is used in a transparent recording medium: ##STR1## where M is a metal atom, and X is a negative ion.
    Type: Grant
    Filed: September 18, 1997
    Date of Patent: April 6, 1999
    Assignee: Nippon Paper Industries Co., Ltd.
    Inventors: Reiji Ohashi, Yukiko Ryu, Tomoaki Nagai, Hidetoshi Yoshioka
  • Patent number: 5883256
    Abstract: A process for removing aromatic heterocyclic compounds from a product-containing solution, in particular a protein solution, by bringing the solution into contact with a support material. The process is preferably carried out following a virus inactivation with acridine or acridine derivatives and makes it possible to remove these virus-inactivating agents from the solution without there being any significant product losses or changes in the biological activity of the solution.
    Type: Grant
    Filed: November 26, 1996
    Date of Patent: March 16, 1999
    Assignee: Behringwerke Aktiengesellschaft
    Inventors: Eckhard Schuler, Karl-Heinz Wenz
  • Patent number: 5879888
    Abstract: A light emitting method of an acridinium ester, comprising reacting said acridinium ester and a superoxide anion, and a method of detecting a substance to be examined, comprising detecting a light emitted by reacting a superoxide anion with an acridinium ester used as a label are described. It is possible to carry out the reaction not under strongly alkaline conditions but around the neutral point and to generate strong luminescence which is stable over a long period of time.
    Type: Grant
    Filed: October 30, 1996
    Date of Patent: March 9, 1999
    Assignee: Iatron Laboratories, Inc.
    Inventors: Masuo Aizawa, Yoshihito Ikariyama, Eiry Kobatake, Minoru Ogasawara, Mitsunao Tanaka
  • Patent number: 5834157
    Abstract: Compounds of the formula ##STR1## are suitable as photoinitiators in free-radical-polymerizable mixtures and are notable for a reduced tendency to diffusion and sublimation than comparable known compounds.
    Type: Grant
    Filed: December 23, 1996
    Date of Patent: November 10, 1998
    Assignee: Agfa-Gevaert AG
    Inventors: Siegfried Scheler, deceased, Klaus-Peter Bergmann, Gerhard Buhr
  • Patent number: 5834462
    Abstract: Novel tricyclic heterocyclic sulfonamide derivatives and sulfonic ester derivatives which have each an antitumor action and are represented by the following general formula (I) and processes for producing the same are provided. These compounds have each an excellent antitumor activity.A sulfonamide derivative or a sulfonic ester derivative represented by the following general formula (I): ##STR1## {G represents an aromatic 5- or 6-membered ring; L represents 0 or --N(R.sup.1)-- (R.sup.1 represents hydrogen or lower alky); and M represents a tricyclic structure selected from among the following ones; ##STR2## ?rings A and B represent each an unsaturated 5- or 6-membered ring; X represents N(R.sup.2), (wherein R.sup.2 represents hydrogen or lower alkyl), or NHCO;Y represents O, S(O).sub.n, C(R.sup.3)(R.sup.4), C(O), N(R.sup.5), CH(R.sup.6)CH(R.sup.7), C(R.sup.8).dbd.C(R.sup.9), N(R.sup.10)C(O), N.dbd.C(R.sup.11), OCH(R.sup.12), S(O).sub.n CH(R.sup.13) or N(R.sup.14)CH(R.sup.15);Z represents nitrogen or C(R.sup.
    Type: Grant
    Filed: March 23, 1995
    Date of Patent: November 10, 1998
    Assignee: Eisai Co., Ltd.
    Inventors: Hiroshi Yoshino, Norihiro Ueda, Jun Niijima, Toru Haneda, Yoshihiko Kotake, Kentaro Yoshimatsu, Tatsuo Watanabe, Takeshi Nagasu, Naoko Tsukahara, Nozomu Koyanagi, Kyosuke Kitoh
  • Patent number: 5792863
    Abstract: An acridine derivative metal complex of formula 1 or formula 2 having a large absorption in the near-infrared range and a reduced absorption in the visible range, which acridine derivative metal complex is used in a transparent recording medium: ##STR1## where M is a metal atom, and X is a negative ion.
    Type: Grant
    Filed: April 15, 1996
    Date of Patent: August 11, 1998
    Assignee: Nippon Paper Industries Co., Ltd.
    Inventors: Reiji Ohashi, Yukiko Ryu, Tomoaki Nagai, Hidetoshi Yoshioka
  • Patent number: 5783699
    Abstract: Acridinium sulfonylamides and isomers, such as phenanthridinium sulfonylamides, may be employed in applications including chemiluminmescent immunoassays. Methods for synthesis of these compounds include contacting an amine with a sulfonylhalide to form a sulfonamide and acylating with an activated carboxylic acid of an acridine or isomer thereof. The N-sulfonyl-9-acridinium carboxamide and isomers may be conjugated to antigens, haptens, antibodies, and nucleic acids for use in chemiluminescent assays.
    Type: Grant
    Filed: May 16, 1995
    Date of Patent: July 21, 1998
    Assignee: Abbott Laboratories
    Inventors: Phillip Gregory Mattingly, Larry Gene Bennett
  • Patent number: 5783696
    Abstract: Chemiluminescent acridinium derivatives of the formula I ##STR1## in which R.sup.4 represents a radical of the formula II or III ##STR2## and A.sup..theta., X--, R.sup.1 -R.sup.3, R.sup.5 and R.sup.6 have the stated meanings, as well as processes for the preparation of the compounds of the formula (I) and the use thereof in chemiluminescence immunoassays.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: July 21, 1998
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Tonio Kinkel, Peter Molz, Erwin Schmidt, Gerd Schnorr, Heinz Jurgen Skrzipczyk
  • Patent number: 5669819
    Abstract: Acridinium sulfonylamides and isomers, such as phenanthridinium sulfonylamides, may be employed in applications including chemiluminmescent immunoassays. Methods for synthesis of these compounds include contacting an amine with a sulfonylhalide to form a sulfonamide and acylating with an activated carboxylic acid of an acridine or isomer thereof. The N-sulfonyl-9-acridinium carboxamide and isomers may be conjugated to antigens, haptens, antibodies, and nucleic acids for use in chemiluminescent assays.
    Type: Grant
    Filed: May 16, 1995
    Date of Patent: September 23, 1997
    Assignee: Abbott Laboratories
    Inventors: Phillip Gregory Mattingly, Larry Gene Bennett
  • Patent number: 5668129
    Abstract: The present invention relates to novel N-substituted azaheterocyclic carboxylic acids and esters thereof in which a substituted alkyl chain forms part of the N-substituent or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation.
    Type: Grant
    Filed: March 27, 1996
    Date of Patent: September 16, 1997
    Assignee: Novo Nordisk A/S
    Inventors: Knud Erik Andersen, Uffe Bang Olsen, Hans Petersen, Frederik Christian Gr.o slashed.nvald, Ursula Sonnewald, Tine Krogh J.o slashed.rgensen, Henrik Sune Andersen
  • Patent number: 5663074
    Abstract: This invention is directed to novel nucleophilic polysubstituted aryl acridinium conjugates and the methods for preparation thereof. The novel nucleophilic polysubstituted aryl acridinium conjugates are useful in biological assays, including novel assays for the determination of Vitamin B.sub.12, folate, cortisol, estradiol, and thromboxane B.sub.2.
    Type: Grant
    Filed: March 17, 1993
    Date of Patent: September 2, 1997
    Assignee: Chiron Diagnostics Corporation
    Inventor: Say-Jong Law
  • Patent number: 5622964
    Abstract: Methods of treating asthma are provided which methods comprise administering to a mammal in need of such treatment an effective amount of a compound of Formula I ##STR1## or a pharmaceutically acceptable salt thereof wherein R.sup.2, R.sup.3, R.sup.4, R.sup.10 and R.sup.11 have any of the meanings given in the specification.
    Type: Grant
    Filed: August 18, 1995
    Date of Patent: April 22, 1997
    Assignee: Zeneca Limited
    Inventors: Cyrus J. Ohnmacht, Jr., Diane A. Trainor, Janet M. Forst, Mark M. Stein, Robert J. Harris
  • Patent number: 5594112
    Abstract: Acridinium compounds represented by the general formula (I) where A is an intervening group which does not have activity for binding with a specific binding substance, Z is a labelling active group which has activity for binding with a specific binding substance, R.sup.1 is a halogen atom, an alkyl group or an aryl group; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, a nitro group, a halogen atom or a carbonyl group, and Y is a counter ion. The acridinium compounds may form conjugates with specific binding substances. The acridinium compounds have high emission efficiency and stability and, hence, are useful as chemiluminescence labelling agents.
    Type: Grant
    Filed: April 28, 1995
    Date of Patent: January 14, 1997
    Assignee: Mochida Pharmaceutical Co., Ltd.
    Inventors: Naofumi Sato, Hiroshi Mochizuki, Toshinori Kanamori
  • Patent number: 5583148
    Abstract: This invention relates to new pyridyl, quinoline and acridine bis-acyloxymethyl compounds; to compositions comprising these compounds; and to processes for their utility as fungicides, bactericides and as inhibitors of the growth of cancer in warm-blooded animals.
    Type: Grant
    Filed: July 15, 1991
    Date of Patent: December 10, 1996
    Assignee: Research Foundation Of State University Of New York
    Inventors: Wayne K. Anderson, Dennis C. Dean
  • Patent number: 5550110
    Abstract: Novel antagonists of endothelin are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin, acute and chronic renal failure, hypertension, myocardial infarction, metabolic, endocrinological, neurological disorders especially cerebral vasospasm, stroke, and head injury, congestive heart failure, endotoxic shock, subarachnoid hemorrhage, arrhythmias, asthma, preeclampsia, atherosclerotic disorders including Raynaud's disease, restenosis, angina, cancer, pulmonary hypertension, ischemic disease, gastric mucosal damage, hemorrhagic shock, ischemic bowel disease, and diabetes.
    Type: Grant
    Filed: June 30, 1994
    Date of Patent: August 27, 1996
    Assignee: Warner-Lambert Company
    Inventors: Wayne L. Cody, Annette M. Doherty, John G. Topliss
  • Patent number: 5543524
    Abstract: Acridinium sulfonylamides and isomers, such as phenanthridinium sulfonylamides, may be employed in applications including chemiluminmescent immunoassays. Methods for synthesis of these compounds include contacting an amine with a sulfonylhalide to form a sulfonamide and acylating with an activated carboxylic acid of an acridine or isomer thereof. The N-sulfonyl-9-acridinium carboxamide and isomers may be conjugated to antigens, haptens, antibodies, and nucleic acids for use in chemiluminescent assays.
    Type: Grant
    Filed: May 16, 1995
    Date of Patent: August 6, 1996
    Assignee: Abbott Laboratories
    Inventors: Phillip G. Mattingly, Larry G. Bennett
  • Patent number: 5521103
    Abstract: New acridinium compounds are provided which comply with formula 1, whereinA is a divalent organic moiety, such as an alkylene chain,X is a group which can be transformed together with C-9 of the acridine into a dioxetane by reaction with hydrogen peroxide, such as an aryloxy group,Y is a counter ion, andZ is a functional group, such as a carboxyl derivative.These acridinium compounds are useful as chemiluminogenic labels for both heterogeneous and homogeneous immunoassays.
    Type: Grant
    Filed: June 24, 1991
    Date of Patent: May 28, 1996
    Assignee: Mochida Pharmaceutical Co., Ltd.
    Inventors: Gijsbert Zomer, Johannus F. C. Stavenuiter
  • Patent number: 5476644
    Abstract: The present invention provides compounds of the formula ##STR1## chelated with a paramagnetic metal ion wherein Z1 and Z2 each represent the atoms necessary to complete a monocyclic or polycyclic carbocyclic or heterocyclic ring system, said Z1 and Z2 independently optionally substituted with R.sup.6 and R.sup.7, respectively;R.sup.l, R.sup.2, R.sup.3 and R.sup.4 are independently carboxyalkyl (C.sub.1 -C.sub.2), --(CH.sub.2).sub.n --C(.dbd.O)--NH--R.sup.8, or --(CH.sub.2).sub.n --C(.dbd.O)--O--R.sup.8R.sup.5 is carboxyalkyl (C.sub.1 -C.sub.2);R.sup.6 and R.sup.7 are independently hydrogen, benzyl, or benzyloxy, said benzyl or benzyloxy optionally substituted with one, two or three substituents selected from the group consisting of amino, isocyanato (--N.dbd.C.dbd.O), isothiocyanato (--N.dbd.C.dbd.S), --NH--C(.dbd.O)--X or --NH--C(.dbd.S)--X;R.sup.8 is alkyl (C.sub.1 -C.sub.20), --(CH.sub.2).sub.m --Ar, or polyhydroxyalkyl (C.sub.1 -C.sub.
    Type: Grant
    Filed: April 13, 1994
    Date of Patent: December 19, 1995
    Assignee: Sterling Winthrop Inc.
    Inventors: Carl R. Illig, Thomas J. Caulfield, John L. Toner, Peng Guo, David L. Ladd
  • Patent number: 5468646
    Abstract: Acridinium sulfonylamides and isomers, such as phenanthridinium sulfonylamides, may be employed in applications including chemiluminmescent immunoassays. Methods for synthesis of these compounds include contacting an amine with a sulfonylhalide to form a sulfonamide and acylating with an activated carboxylic acid of an acridine or isomer thereof. The N-sulfonyl-9-acridinium carboxamide and isomers may be conjugated to antigens, haptens, antibodies, and nucleic acids for use in chemiluminescent assays.
    Type: Grant
    Filed: January 3, 1995
    Date of Patent: November 21, 1995
    Assignee: Abbott Laboratories
    Inventors: Phillip G. Mattingly, Larry G. Bennett
  • Patent number: 5468870
    Abstract: Dye-donor element for use according to thermal dye sublimation transfer comprising a support having thereon a dye layer containing a dye corresponding to the following formula ##STR1## wherein Z represents CN, COOR.sup.1 or CONR.sup.2 R.sup.3 ;R.sup.1, R.sup.2 and R.sup.3 each independently represent hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, or R.sup.2 and R.sup.3 together represent the necessary atoms to close a heterocyclic nucleus or substituted heterocyclic nucleus;Y represents OR.sup.4 or NR.sup.5 R.sup.6 or CN;R.sup.4 represents hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, SO.sub.2 R.sup.7, COR.sup.7, CSR.sup.7, POR.sup.7 R.sup.8 ;R.sup.5 and R.sup.6 each independently has one of the significances given to R.sup.4 or represent substituted or unsubstituted amino, or R.sup.5 and R.sup.
    Type: Grant
    Filed: October 20, 1994
    Date of Patent: November 21, 1995
    Assignee: AGFA-GAVAERT, N.V.
    Inventor: Luc J. Vanmaele
  • Patent number: 5457122
    Abstract: The phenylalkan(en)oic acids of the formula: ##STR1## as defined herein, possess an antagonistic activity on leukotriene B.sub.4.
    Type: Grant
    Filed: July 13, 1993
    Date of Patent: October 10, 1995
    Assignee: Ono Pharmaceutical Co., Ltd.
    Inventors: Mitoshi Konno, Takahiko Nakae, Nobuyuki Hamanaka
  • Patent number: 5455253
    Abstract: Compounds of formula I ##STR1## wherein R.sup.2, R.sup.3, R.sup.4, R.sup.10 and R.sup.11 have any of the meanings given in the specification, and their pharmaceutically acceptable salts are useful in the treatment of urinery incontinence. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.
    Type: Grant
    Filed: April 14, 1994
    Date of Patent: October 3, 1995
    Assignee: Zeneca Limited
    Inventors: Cyrus J. Ohnmacht, Jr., Diane Trainor, Janet M. Forst, Mark M. Stein, Robert J. Harris
  • Patent number: 5449556
    Abstract: A method for the detection of an analyte in a fluid sample using liposomes encapsulating acridinium esters (lumisomes). Hydrophilic polysubstituted aryl acridinium esters are useful as chemiluminescent markers and can be encapsulated within liposome vesicles without significant leakage of the esters from the vesicles. The lumisomes can be coupled to molecules with biological activity, such as antigens, antibodies, and nucleic acids, and used in luminescent assays.
    Type: Grant
    Filed: March 17, 1993
    Date of Patent: September 12, 1995
    Assignee: Ciba Corning Diagnostics Corp.
    Inventors: Say-Jong Law, Uri Piran
  • Patent number: 5449778
    Abstract: Novel cyclic amino acids which are useful in preparing biologically active peptides as well as a process for the preparation of D and L enantiomers of the cyclic amino acids are described where an N-protected derivative of the racemic cyclic amino acid is treated with (-)cinchonidine and the resulting salt resolved into the desired enantiomers, as well as derivatives thereof and valuable intermediates used in the process.
    Type: Grant
    Filed: September 8, 1994
    Date of Patent: September 12, 1995
    Assignee: Warner-Lambert Company
    Inventors: Vladimir Beylin, Huai G. Chen, Om P. Goel, Mark E. Marlatt, John G. Topliss
  • Patent number: 5438139
    Abstract: Acridinium compounds represented by the general formula (I) where A is an intervening group which does not have activity for binding with a specific binding substance, Z is a labelling active group which has activity for binding with a specific binding substance, R.sup.1 is a halogen atom, an alkyl group or an aryl group; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, a nitro group, a halogen atom or a carbonyl group, and Y is a counter ion. The acridinium compounds may form conjugates with specific binding substances. The acridinium compounds have high emission efficiency and stability and, hence, are useful as chemiluminescence labelling agents.
    Type: Grant
    Filed: January 31, 1994
    Date of Patent: August 1, 1995
    Assignee: Mochida Pharmaceutical Co., Ltd.
    Inventors: Naofumi Sato, Hiroshi Mochizuki, Toshinori Kanamori
  • Patent number: 5395938
    Abstract: A unique class of chemiluminescent labels containing biotin substitution that are suitable for chemiluminescent assays using inter alia a streptavidin and/or avidin conjugate. The chemiluminescent labels of the invention have the ability to bind to streptavidin and/or avidin per se or to streptavidin and/or avidin conjugated with an analyte. Label structures are disclosed that have hydrolytic stability to meet the most demanding commercial assay conditions. The invention encompasses conjugates containing associated versions of the labeling compounds, assays and kits for performing such assay utilizing the conjugates.
    Type: Grant
    Filed: August 21, 1992
    Date of Patent: March 7, 1995
    Assignee: Nichols Institute Diagnostics
    Inventor: Kastooriranganathan Ramakrishnan