Polycyclo Ring System Having The Hetero Ring As One Of The Cyclos Patents (Class 549/220)
  • Patent number: 6270695
    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: July 21, 1999
    Date of Patent: August 7, 2001
    Assignee: Lumigen, Inc.
    Inventors: Hashem Akhavan-Tafti, Zahra Arghavani, Renuka DeSilva
  • Patent number: 6211167
    Abstract: The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infrections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.
    Type: Grant
    Filed: June 14, 2000
    Date of Patent: April 3, 2001
    Assignee: Tularik Inc.
    Inventor: Jonathan B. Houze
  • Patent number: 6162929
    Abstract: A process for the manufacture of bisphosphine oxide compounds and bisphosphonates as intermediates for the production of bisphosphine ligands, in which in a single step processa) a phosphine oxide compound is reacted in an organic solvent at -70.degree. C. to 20.degree. C. with 0.5-3 eq. of a lithium or magnesium amide compound,b) 0.5-3 eq. of oxidatively-acting metal salt or metal salt complex are added to the suspension obtained in stage a) in a temperature range of -70.degree. C. to 20.degree. C., with a racemate of a bisphosphine oxide compound being obtained;c) a racemate cleavage is carried out if desired; andd) the bisphosphonates obtained in stage b) or c) are converted into bisphosphine oxides.
    Type: Grant
    Filed: December 15, 1998
    Date of Patent: December 19, 2000
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Joseph Foricher, Rudolf Schmid
  • Patent number: 6110962
    Abstract: This invention provides compounds of Formula I having the structure ##STR1## wherein A is hydrogen, halogen, or OH;B and D are each, independently, hydrogen, halogen, CN, alkyl of 1-6 carbon atoms, aryl, aralkyl of 6-12 carbon atoms, nitro, amino or OR;R is hydrogen, alkyl of 1-6 carbon atoms, --COR.sup.1, --CH.sub.2 CO.sub.2 R.sup.1, --CH(R.sup.1a)CO.sub.2 R.sup.1, or --SO.sub.2 R.sup.1 ;R.sup.1 and R.sup.1a are each, independently, hydrogen, alkyl of 1-6 carbon atoms, aralkyl of 6-12 carbon atoms or aryl;E is S, SO, SO.sub.2, O;X is hydrogen, halogen, alkyl of 1-6 carbon atoms, CN, perfluoroalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, aryloxy, arylalkoxy of 6-12 carbon atoms, nitro, amino, alkylsulfanyl of 1-6 carbon atoms, arylsulfanyl, pyridylsulfanyl, 2-N,N-dimethylaminoethylsulfanyl, or --OCH.sub.2 CO.sub.2 R.sup.1b ;R.sup.1b is hydrogen or alkyl of 1-6 carbon atoms;Y and Z are each, independently, hydrogen or OR.sup.2 ;R.sup.
    Type: Grant
    Filed: May 10, 1999
    Date of Patent: August 29, 2000
    Assignee: American Home Products Corporation
    Inventors: Jay E. Wrobel, Arlene J. Dietrich, Zenan Li
  • Patent number: 6090951
    Abstract: Novel methods for the preparation of sidechain-bearing taxanes, comprising the preparation of an oxazoline compound, coupling the oxazoline compound with a taxane having a hydroxyl group directly bonded at C-13 thereof to form an oxazoline sidechain-bearing taxane, and opening the oxazoline ring of the oxazoline sidechain-bearing taxane so formed. Novel compounds prepared by the methods of the present invention are also provided.
    Type: Grant
    Filed: August 25, 1997
    Date of Patent: July 18, 2000
    Inventors: Michael A. Poss, Jerome L. Moniot, Ivan D. Trifunovich, David J. Kucera, John K. Thottahil, Shu-Hui Chen, Jianmei Wei
  • Patent number: 6087347
    Abstract: Estratriene derivatives of the following formula have a powerful inhibitory effect on estrone sulfatase and are hence useful for the prophylaxis or treatment of diseases caused by estrogens, such as breast cancer, uterine cancer, ovarian cancer, endometriosis, adenomyosis uteri and mastopathy. ##STR1## wherein one of A and B represents C.dbd.O or CH.sub.2 and the other represents O or NH; and R represents --SO.sub.2 NR.sup.1 R.sup.2 or --PO(OM).sub.2 in which R.sup.1 and R.sup.2 each independently represent a hydrogen atom or a lower alkyl group and M represents a hydrogen atom or an alkali metal; provided that, when one of A and B represents NH, the other represents C.dbd.O.
    Type: Grant
    Filed: March 12, 1999
    Date of Patent: July 11, 2000
    Assignee: Teikoku Hormone Mfg. Co., Ltd.
    Inventors: Naoyuki Koizumi, Shigehiro Takegawa, Shigeki Iwashita, Tomoko Kawachi, Mamoru Mieda, Tomohito Fujii
  • Patent number: 6001659
    Abstract: Chemiluminescent electron-rich aryl-substituted 1,2-dioxetane compounds are disclosed in which the aryl group is poly-substituted with suitable electron-donating groups such that the light-emitting pattern of the molecule results in a very high luminescent count, thus providing for a sensitive and precise assay for haptens, analytes, polynucleotides and the like. These substituted aryl-containing 1,2-dioxetane compounds can be used as direct labels in an immunoassay or when derivatized with an appropriate leaving group, can be used as a substrate for a enzyme immunoassay. The unusual chemiluminescence of the compounds allows the timing of the luminescent reaction to be exactly controlled.
    Type: Grant
    Filed: May 9, 1995
    Date of Patent: December 14, 1999
    Assignee: Abbott Laboratories
    Inventors: Nai-Yi Wang, Roger C. Hu
  • Patent number: 6001561
    Abstract: Chemiluminescent electron-rich aryl-substituted 1,2-dioxetane compounds are disclosed in which the aryl group is poly-substituted with suitable electron-donating groups such that the light-emitting pattern of the molecule results in a very high luminescent count, thus providing for a sensitive and precise assay for haptens, analytes, polynucleotides and the like. These substituted aryl-containing 1,2-dioxetane compounds can be used as direct labels in an immunoassay or when derivatized with an appropriate leaving group, can be used as a substrate for a enzyme immunoassay. The unusual chemiluminescence of the compounds allows the timing of the luminescent reaction to be exactly controlled.
    Type: Grant
    Filed: May 9, 1995
    Date of Patent: December 14, 1999
    Assignee: Abbott Laboratories
    Inventors: Nai-Yi Wang, Roger C. Hu
  • Patent number: 5985856
    Abstract: The present invention is drawn to water soluble derivatives aliphatic acid aromatic secondary and tertiary amine containing drugs. The present invention is further drawn to methods of making water soluble derivatives of aliphatic and aromatic secondary and tertiary amine containing drugs.
    Type: Grant
    Filed: December 30, 1998
    Date of Patent: November 16, 1999
    Assignee: University of Kansas
    Inventors: Valentino Stella, Jeffrey P. Krise, Jan J. Zygmunt, Ingrid Gunda Georg
  • Patent number: 5981514
    Abstract: Disclosed herein are compounds of the formula ##STR1## or the pharmaceutically acceptable salts thereof wherein R.sub.1 is alkyl of 1-6 carbon atoms;A is alkylene having from 2-5 carbon atoms, each of which carbon atoms is substituted with R.sub.2, where each R.sub.2 is independently hydrogen or C.sub.1 -C.sub.6 alkyl;R.sub.3 is C.sub.1 -C.sub.6 alkyl;Y and Y.sub.1 are hydrogen or halogen; andR.sub.4 is hydrogen or --PO.sub.3 H,which compounds are water soluble and can be used for the treatment of arrhythmias.
    Type: Grant
    Filed: February 12, 1999
    Date of Patent: November 9, 1999
    Inventor: John C. Somberg
  • Patent number: 5981768
    Abstract: A new class of stable dioxetanes bears a polycyclic stabilizing group and aryloxy moiety, the oxygen atom of which is provided with a protective group which can be removed by an enzymatic or chemical trigger admixed with the dioxetane. The polycyclic stabilizing group is preferably spiroadamantane. The group further bears an alkoxy, aryloxy, aralkyloxy or cycloalkyloxy moiety which is partially or completely substituted with halogens, particularly fluorine and chlorine. Proper selection of electron active groups on the stabilizing moiety, the aryl group and the OR group yields enhanced enzyme kinetics, superior light intensity and excellent detection sensitivity in various assays.
    Type: Grant
    Filed: September 21, 1998
    Date of Patent: November 9, 1999
  • Patent number: 5973160
    Abstract: Novel methods for the preparation of sidechain-bearing taxanes, comprising the preparation of an oxazoline compound, coupling the oxazoline compound with a taxane having a hydroxyl group directly bonded at C-13 thereof to form an oxazoline sidechain-bearing taxane, and opening the oxazoline ring of the oxazoline sidechain-bearing taxane so formed. Novel compounds prepared by the methods of the present invention are also provided.
    Type: Grant
    Filed: February 13, 1996
    Date of Patent: October 26, 1999
    Inventors: Michael A. Poss, Jerome L. Moniot, Ivan D. Trifunovich, David J. Kucera, John K. Thottahil, Shu-Hui Chen, Jianmei Wei
  • Patent number: 5969015
    Abstract: Compositions, comprising (i) a halogen-containing polymeric material, and(ii) at least one phosphite of formula I ##STR1## wherein n is a number from 1 to 6,R is a divalent linking group of formulae as defined herein as well as of novel compounds of formula I and their use as stabilisers.
    Type: Grant
    Filed: September 10, 1997
    Date of Patent: October 19, 1999
    Assignee: Witco Vinyl Additives GmbH
    Inventors: Horst Zinke, Karl Josef Kuhn, Wolfgang Wehner
  • Patent number: 5962438
    Abstract: A novel estrogen derivative represented by the formula: ##STR1## is useful for treating or preventing diseases caused by estrogen deficiency.
    Type: Grant
    Filed: October 17, 1997
    Date of Patent: October 5, 1999
    Assignee: Sumitomo Pharmaceuticals Company, Limited
    Inventors: Michihiro Yamamoto, Akira Sasaki, Takashi Katsumata, Naomi Tsushima, Hideyuki Harada
  • Patent number: 5958905
    Abstract: Phosphoramidates and phosphinic amides and related compounds are provided. Also provided are methods that use the compounds for modulating the activity of the endothelin family of peptides are provided. In particular, compounds having formula: ##STR1## in which A, B, R.sup.1 and R.sup.2 are as described are provided. Also provided are methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these compounds or prodrugs thereof. Methods for elucidating the physiological and pathophysiological roles of endothelin, as well as isolating endothelin receptors are also provided.
    Type: Grant
    Filed: March 26, 1996
    Date of Patent: September 28, 1999
    Assignee: Texas Biotechnology Corporation
    Inventors: Ming Fai Chan, Erik Joel Verner
  • Patent number: 5955453
    Abstract: Membrane-permeant phosphoinositides, including phosphatidylinositol phosphate esters, are described. A membrane-permeant phosphoinositide includes groups that neutralize the charges of the phosphate moieties of the phosphoinositide. A cell can be treated with the membrane-permeant phosphoinositide, which is then absorbed into the cell. The neutralizing groups can be removed intracellularly to afford the charged phosphoinositide.
    Type: Grant
    Filed: April 24, 1998
    Date of Patent: September 21, 1999
    Assignee: The Regents of the University of California
    Inventors: Roger Y. Tsien, Tao Jiang
  • Patent number: 5948631
    Abstract: The subject matter of the invention is a stable mixture for the detection of alkaline phosphatase, wherein it contains the N-methylglucamine salt of o-cresolphthalein monophosphoric acid and N-methylglucamine as well as an analytical element for the detection of alkaline phosphatase with a matrix that carries this mixture. In addition the invention concerns a method for the determination of alkaline phosphatase using a salt of o-cresolphthalein monophosphoric acid, wherein the sample is brought into contact with a mixture according to the invention or an analytical element according to the invention and a change in color is observed in the presence of alkaline phosphatase.A subject matter of the invention is also a salt of o-cresolphthalein monophosphoric acid with N-methylglucamine as well as a process for producing such a salt.
    Type: Grant
    Filed: August 7, 1997
    Date of Patent: September 7, 1999
    Assignee: Roche Diagnostics GmbH
    Inventors: Rolf Nagel, Steffen Bossert-Reuther, Thomas Zeibig
  • Patent number: 5910600
    Abstract: A bisphosphite compound of the following formula (A): ##STR1## wherein --Ar--Ar-- is a bisarylene group represented by any one of the formulae (A-I) to (A-III) defined in the specification, and each of Z.sub.1 to Z.sub.4 is a C.sub.4-20 aromatic or heteroaromatic group which may have a substituent, wherein each of substituents on carbon atoms of an aromatic ring adjacent to the carbon atom bonded to the oxygen atom in each of Z.sub.1 to Z.sub.4, is a C.sub.0-2 group, and each pair of Z.sub.1 and Z.sub.2, and Z.sub.3 and Z.sub.4, are not bonded to each other.
    Type: Grant
    Filed: April 28, 1997
    Date of Patent: June 8, 1999
    Assignee: Mitsubishi Chemical Corporation
    Inventors: Hisao Urata, Hiroaki Itagaki, Eitaro Takahashi, Yasuhiro Wada, Yoshiyuki Tanaka, Yasukazu Ogino
  • Patent number: 5872273
    Abstract: A novel diphosphine compound of the formula (I): ##STR1## where R.sup.1 and R.sup.2 represent independently cycloalkyl, unsubstituted or substituted phenyl, or a five-membered heteroaromatic ring. The compound is useful as a ligand for an asymmetric reaction, in particular, as an asymmetric hydrogenation catalyst.
    Type: Grant
    Filed: December 22, 1997
    Date of Patent: February 16, 1999
    Assignee: Takasago International Corporation
    Inventors: Takao Saito, Tohru Yokozawa, Xiaoyaong Zhang, Noburo Sayo
  • Patent number: 5858995
    Abstract: This invention relates to a novel heterocyclic compound represented by formula (I), wherein each symbol is as defined in the specification and a pharmaceutically acceptable salt thereof which are the inhibitors of bone resorption and bone metabolism, to processes for preparation thereof, to a pharmaceutical composition comprising the same and to a method for the treatment of diseases caused by abnormal bone metabolism in human being or an animal.
    Type: Grant
    Filed: October 25, 1996
    Date of Patent: January 12, 1999
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Yoshio Kawai, Hitoshi Yamazaki, Natsuko Kayakiri, Kousei Yoshihara, Takumi Yatabe, Teruo Oku
  • Patent number: 5847161
    Abstract: A new class of stable dioxetanes bears a polycyclic stabilizing group and aryloxy moiety, the oxygen atom of which is provided with a protective group which can be removed by an enzymatic or chemical trigger admixed with the dioxetane. The polycyclic stabilizing group is preferably spiroadamantane. The group further bears an alkoxy, aryloxy, aralkyloxy or cycloalkyloxy moiety which is partially or completely substituted with halogens, particularly fluorine and chlorine. Proper selection of electron active groups on the stabilizing moiety, the aryl group and the OR group yields enhanced enzyme kinetics, superior light intensity and excellent detection sensitivity in various assays.
    Type: Grant
    Filed: June 13, 1997
    Date of Patent: December 8, 1998
  • Patent number: 5840925
    Abstract: Described herein are novel trioxane dimers of structure ##STR1## which possess antiproliferative and antitumor activities.
    Type: Grant
    Filed: December 2, 1996
    Date of Patent: November 24, 1998
    Assignee: Hauser, Inc.
    Inventors: Qun Y. Zheng, Christopher Murray, Randall J. Daughenbaugh, Poonsakdi Ploypradith, Gary H. Posner
  • Patent number: 5840919
    Abstract: Novel 1,2-dioxetanes with improved chemiluminescent properties, such as signal intensity, S/N ratio, T1/2, etc. are provided by spiroadamantyl 1,2-dioxetanes, wherein the remaining carbon atom of the ring bears an alkoxy, aryloxy, or arylalkoxy substituent, and either a phenyl or naphthyl ring, this aromatic ring bearing, at the meta position on the phenyl group, or a non-conjugated position on the naphthyl ring, a OX moiety wherein X is an enzyme-cleavable group, which when removed from the dioxetane, leaves the oxyanion which decomposies with chemiluminescence, the aryl ring further bearing an electron active substituent Z. The nature and placement of the Z substituent, at a position not adjacent the point of attachment to the dioxetane ring, strongly influences the properties of the dioxetane. Assays, as well as kits for the performance of those assays, include the dioxetane, an enzyme capable of cleaving the X group, and in certain cases, membranes and chemiluminscent enhancement agents.
    Type: Grant
    Filed: October 17, 1995
    Date of Patent: November 24, 1998
  • Patent number: 5840917
    Abstract: A phosphorylamide derivative represented by the general formula (I): ##STR1## wherein R represents an amino group that may be substituted, or a salt thereof, possesses potent antibacterial activity against Helicobacter bacterium, especially Helicobacter pylori, and is useful for prevention or treatment of digestive diseases caused by Helicobacter bacterium, solely or in combination with an antacid or an acid secretion inhibitor.
    Type: Grant
    Filed: December 6, 1996
    Date of Patent: November 24, 1998
    Assignee: Takeda Chemical Industries, Ltd.
    Inventors: Satoru Oi, Hideaki Nagaya, Nobuhiro Inatomi, Masafumi Nakao, Hidefumi Yukimasa
  • Patent number: 5837669
    Abstract: The invention relates to compounds of formula: ##STR1## The invention also relates to a process for the preparation of the said compounds, which consists in:a) reacting dianhydro-1,4:3,6-D-glucitol with a compound of formula RCOOR' or RCH.sub.2 Y in the presence of a catalyst to form compounds of formula: ##STR2## in which: Y represents a halogen or an alkyl or arylsulfonic radical,R' represents a hydrogen atom or an alkyl radical having from 1 to 6 carbon atoms,R represents a saturated or unsaturated linear or branched alkyl radical containing from 5 to 21 carbon atoms,x represents CO or CH.sub.2 ;b) reacting the product of step a) with phosphorus oxychloride, a base and an anhydrous solvent, to form the compounds of formula (I) and/or (II), and optionally in separating them.The compounds which form the subject of the invention can be used in the field of surfactants, in particular for the preparation of cosmetic or hair compositions.
    Type: Grant
    Filed: March 26, 1997
    Date of Patent: November 17, 1998
    Assignee: Ceca S.A.
    Inventors: Serge Petit, Stephane Fouquay, Daniel Bernard
  • Patent number: 5814657
    Abstract: Compounds of the formula ##STR1## wherein the variables are defined as in the specification, are capable of lowering introaocular pressure in the eye of a mammal.
    Type: Grant
    Filed: November 21, 1997
    Date of Patent: September 29, 1998
    Assignee: Allergan
    Inventors: Robert M. Burk, David F. Woodward
  • Patent number: 5808162
    Abstract: A novel chiral unsymmetric diphosphine compound of formula (I): ##STR1## wherein Ar.sup.1 and Ar.sup.2, which are different from each other, each represent a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a pyridyl group, a quinolyl group, an isoquinolyl group, a furfuryl group, a benzofurfuryl group, a thienyl group, or a benzothienyl group, and a transition metal complex containing the diphosphine compound as a ligand. The complex catalyzes various asymmetric synthesis reactions, e.g., asymmetric hydrogenation or asymmetric hydrosilylation, exhibiting excellent performance in selectivity, conversion and catalytic activity, to provide a product of desired absolute configuration at high optical purity and in high yield.
    Type: Grant
    Filed: July 18, 1996
    Date of Patent: September 15, 1998
    Assignee: Takasago International Corporation
    Inventors: Noboru Sayo, Xiaoyong Zhang, Tatsuya Omoto, Tohru Yokozawa, Tetsuro Yamasaki, Hidenori Kumobayashi
  • Patent number: 5808102
    Abstract: Novel methods for the preparation of sidechain-bearing taxanes, comprising the preparation of an oxazoline compound, coupling the oxazoline compound with a taxane having a hydroxyl group directly bonded at C-13 thereof to form an oxazoline sidechain-bearing taxane, and opening the oxazoline ring of the oxazoline sidechain-bearing taxane so formed. Novel compounds prepared by the methods of the present invention are also provided.
    Type: Grant
    Filed: August 22, 1997
    Date of Patent: September 15, 1998
    Assignee: Bristol-Myers Squibb Company
    Inventors: Michael A. Poss, Jerome L. Moniot, Ivan D. Trifunovich, David J. Kucera, John K. Thottahil, Shu-Hui Chen, Jianmei Wei
  • Patent number: 5795981
    Abstract: Squarylium compounds of the formula: ##STR1## (in which Q.sup.1 and Q.sup.2 are each a chromophoric group having an aromatic unsaturated system conjugated with the squarylium ring and such that in the compounds of formulae Q.sup.1 CH.sub.2 R.sup.1 and Q.sup.2 CH.sub.2 R.sup.2 the methylene hydrogens are active hydrogens, R.sup.1 and R.sup.2 are each independently a hydrogen atom or an aliphatic or cycloaliphatic group, and R.sup.3 and R.sup.4 are each independently a hydrogen atom, or an acyl, aliphatic, cycloaliphatic, aromatic or heterocyclic group, subject to the proviso that one of R.sup.3 and R.sup.4 may be an amino or substituted amino group, or one of R.sup.3 and R.sup.4 is a hydrogen atom and the other is an organosulfonyl group, or R.sup.3 and R.sup.4 together with the intervening nitrogen atom form a nitrogenous heterocyclic ring) are useful as near infra-red absorbers.
    Type: Grant
    Filed: December 16, 1996
    Date of Patent: August 18, 1998
    Assignee: Polaroid Corporation
    Inventors: John W. Lee, Donald A. McGowan, Mark R. Mischke, Socorro M. Ramos, Stephen J. Telfer
  • Patent number: 5756770
    Abstract: A novel synthesis of 1,2-dioxetane phosphate alkali metal salts and novel intermediates employed in this synthesis are disclosed. A hydroxyaryl enol ether alkali metal salt having the formula: ##STR1## wherein T can be an unsubstituted or substituted adamant-2'-ylidene group, R.sup.3 can be a methyl group, Y can be a phenyl group and M.sup.+ can be a sodium cation, is reacted with a phosphorohalidate to give the corresponding enol ether ethylene phosphate, which is then reacted with an alkali metal cyanide to give the corresponding enol ether cyanoethyl phosphate diester alkali metal salt intermediate. Singlet oxygen addition to this enol ether cyanoethyl phosphate diester alkali metal salt intermediate to give the corresponding 1,2-dioxetane cyanoethyl phosphate diester alkali metal salt, followed by .beta.-elimination of the cyanoethyl group using an alkali metal hydroxide or the like, gives the corresponding 1,2-dioxetane phosphate alkali metal salt.
    Type: Grant
    Filed: December 20, 1990
    Date of Patent: May 26, 1998
  • Patent number: 5750516
    Abstract: This invention provides a phosphoric diester of formula (I) which is available on di-esterification of phosphoric acid with L-ascorbic acid involving its 5-hydroxyl group and tocopherol involving its hydroxyl group or a pharmacologically acceptable salt thereof. ##STR1## The compound of the invention can be used with advantage as an antioxidant (radical-scavenging) agent and a prophylactic and therapeutic agent for ischemic organ disorders (e.g. myocardial infarction, heart failure, arrhythmia, cerebral infarction, stroke (cerebral apoplexy), renal failure, etc.).
    Type: Grant
    Filed: September 30, 1996
    Date of Patent: May 12, 1998
    Assignee: Senju Pharmaceutical Co., Ltd.
    Inventors: Masayuki Nakamura, Kazumi Ogata, Takahiro Sakaue, Noriko Saito, Masahito Iemura
  • Patent number: 5721355
    Abstract: Compounds useful to attach a fluorescein label to an oligonucleotide are disclosed. To create these compounds, oxygen groups on the fluorescein moiety are protected (e.g. with acyl groups). One then links a phosphoramidite to the fluorescein moiety via an amide or thiourea linkage to an active site on the fluorescein ring. The resulting compound can then be directly linked to an oligonucleotide as it is being formed in an automated synthesizer and then deprotected using the same deprotection conditions as are used to deprotect the oligonucleotides. Such compounds are, inter alia, useful to create labelled primers for DNA sequencing.
    Type: Grant
    Filed: June 25, 1996
    Date of Patent: February 24, 1998
    Assignee: Pharmacia Biotech Inc.
    Inventor: Charles K. Brush
  • Patent number: 5719182
    Abstract: Novel indane and indene derivatives are described which are endothelin receptor antagonists.
    Type: Grant
    Filed: May 16, 1995
    Date of Patent: February 17, 1998
    Assignee: SmithKline Beecham Corporation
    Inventors: Russell Donovan Cousins, John Duncan Elliott, Maria Amparo Lago, Jack Dale Leber, Catherine Elizabeth Peishoff
  • Patent number: 5714621
    Abstract: Compounds of the formula ##STR1## where W is (CH.sub.2).sub.n where n is 1 or 2, or n is 0 and W represents lower alkyl groups attached to each oxygen;m is an integer between 1 and 8;R.sub.1 is COOH or a pharmaceutically acceptable salt thereof, COOR.sub.4, CONR.sub.5 R.sub.6, CONR.sub.5 SO.sub.2 R.sub.7, CH.sub.2 OH, CH.sub.2 OR.sub.7, CH.sub.2 O--COR.sub.7, CH.sub.2 O--CONR.sub.5,R.sub.7, CH.sub.2 OCOOR.sub.7, CH.sub.2 NH.sub.2, CH.sub.2 NR.sub.5 R.sub.6, CH.sub.2 NR.sub.5 COR.sub.7, CHO, CH(OR.sub.8).sub.2, CHOR.sub.9 O, --COR.sub.10, CR.sub.10 (OR.sub.8).sub.2, or CR.sub.10 OR.sub.9 O, where R.sub.4 is an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R.sub.4 is phenyl or lower alkylphenyl, R.sub.5 and R.sub.6 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or phenyl or lower alkylphenyl, R.sub.7 is alkyl of 1 to 10 carbons, phenyl or lower alkylphenyl, R.sub.8 is lower alkyl, and R.sub.
    Type: Grant
    Filed: February 27, 1996
    Date of Patent: February 3, 1998
    Assignee: Allergan
    Inventors: Robert M. Burk, David F. Woodward
  • Patent number: 5710288
    Abstract: Compounds of the formula ##STR1## where the symbols have the meaning defined in the specification, are capable of lowering intraocular pressure in the eye of a mammal.
    Type: Grant
    Filed: May 3, 1996
    Date of Patent: January 20, 1998
    Assignee: Allergan
    Inventors: Robert M. Burk, David F. Woodward
  • Patent number: 5693868
    Abstract: The present invention provides a method for producing novel optically active diphosphine compounds ?2,2'-bis(di-substituted phosphino)-1,1'-binaphthyl compounds! having a selectivity (chemoselectivity or enantioselectivity) and catalytic activity different from those of conventional BINAP compounds. In a method of the present invention for producing an optically active diphosphine compound (i.e., 2,2-bis(di-substituted phosphino)-1,1'-binaphthyl), 2,2'-bis(trifluoromethanesulfonyloxy)-1,1'-binaphthyl is reacted, in the presence of a transition metal-phosphine complex, with a phosphineoxide compound represented by the following general formula:A.sub.
    Type: Grant
    Filed: October 30, 1996
    Date of Patent: December 2, 1997
    Assignee: Takasago International Corporation
    Inventors: Noboru Sayo, Xiaoyong Zhang, Tatsuya Ohmoto, Akifumi Yoshida, Tohru Yokozawa
  • Patent number: 5679700
    Abstract: Novel phosphinic acid-containing peptidyl compounds of formula I are found to be useful inhibitors of matrix metalloendoproteinase-mediated diseases including osteoarthritis, rheumatoid arthritis, septic arthritis, tumor invasion in certain cancers, periodontal disease, corneal ulceration, proteinuria, dystrophobic epidermolysis bullosa, and coronary thrombosis associated with atherosclerotic plaque rupture. These inhibitors may also be useful in preventing the pathological sequelae following a traumatic injury that could lead to permanent disability. These compounds may also have utility as a means for birth control by preventing ovulation or implantation.
    Type: Grant
    Filed: November 9, 1995
    Date of Patent: October 21, 1997
    Assignee: Merck & Co., Inc.
    Inventors: Charles G. Caldwell, Philippe L. Durette, Joung L. Goulet, William K. Hagmann, Soumya P. Sahoo
  • Patent number: 5679803
    Abstract: A new class of stable dioxetanes bears a polycyclic stabilizing group and aryloxy moiety, the oxygen atom of which is provided with a protective group which can be removed by an enzymatic or chemical trigger admixed with the dioxetane. The polycyclic stabilizing group is preferably spiroadamantane. The group further bears an alkoxy, aryloxy, aralkyloxy or cycloalkyloxymoiety which is partially or completely substituted with halogens, particularly fluorine and chlorine. Proper selection of electron active groups on the stabilizing moiety, the aryl group and the OR group yields enhanced enzyme kinetics, superior light intensity and excellent detection sensitivity in various assays.
    Type: Grant
    Filed: October 25, 1995
    Date of Patent: October 21, 1997
  • Patent number: 5668176
    Abstract: Phenoxyphenylacetic acids and derivatives of the general structural formula I ##STR1## have endothelin antagonist activity and are useful in treating cardiovascular disorders, such as hypertension, postischemic renal failure, vasospasm, cerebral and cardiac ischemia, myocardial infarction, endotoxic shock, benign prostatic hyperplasia, inflammatory diseases including Raynaud's disease and asthma.
    Type: Grant
    Filed: October 18, 1996
    Date of Patent: September 16, 1997
    Assignee: Merck & Co. Inc.
    Inventors: Scott W. Bagley, Theodore P. Broten, Prasun K. Chakravarty, Daljit S. Dhanoa, Kenneth J. Fitch, William J. Greenlee, Nancy Jo Kevin, Gerard R. Kieczykowski, Douglas J. Pettibone, James R. Tata, Ralph A. Rivero, Thomas F. Walsh, David L. Williams, Jr., Jay M. Matthews, Richard B. Toupence
  • Patent number: 5660976
    Abstract: This invention provides a hepatic graft preservative composition containing a phosphoric acid diester compound of the formula: ##STR1## (wherein R.sub.1 and R.sub.2 are the same or different and each represents a hydrogen atom or a methyl group) or a pharmacologically acceptable salt thereof and a method for viable preservation of the hepatic graft using the above substance.The hepatic graft preservative composition and hepatic graft preserving method of this invention inhibit hepatic microcirculation disturbance following cold storage-reperfusion of the liver to effectively prevent necrosis of hepatocytes and is, therefore, useful for the preservation of the hepatic graft.
    Type: Grant
    Filed: June 13, 1995
    Date of Patent: August 26, 1997
    Assignee: Senju Pharmaceutical Co., Ltd.
    Inventors: Yuzuru Ishimura, Makoto Suematsu, Kenichi Yoshida
  • Patent number: 5656750
    Abstract: Squarylium compounds of the formula: ##STR1## (in which Q.sup.1 and Q.sup.2 are each a chromophoric group having an aromatic unsaturated system conjugated with the squarylium ring and such that in the compounds of formulae Q.sup.1 CH.sub.2 R.sup.1 and Q.sup.2 CH.sub.2 R.sup.2 the methylene hydrogens are active hydrogens, R.sup.1 and R.sup.2 are each independently a hydrogen atom or an aliphatic or cycloaliphatic group, and R.sup.3 and R.sup.4 are each independently a hydrogen atom, or an acyl, aliphatic, cycloaliphatic, aromatic or heterocyclic group, subject to the proviso that one of R.sup.3 and R.sup.4 may be an amino or substituted amino group, or one of R.sup.3 and R.sup.4 is a hydrogen atom and the other is an organosulfonyl group, or R.sup.3 and R.sup.4 together with the intervening nitrogen atom form a nitrogenous heterocyclic ring) are useful as near infra-red absorbers.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: August 12, 1997
    Assignee: Polaroid Corporation
    Inventors: Richard M. Allen, Peter K. Chu
  • Patent number: 5650404
    Abstract: This invention provides a therapeutic composition for pancreatitis which comprises a phosphoric diester compound of the following formula or a pharmacologically acceptable salt thereof ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and each represents hydrogen or methyl. The pharmaceutical composition of this invention can be used with advantage in the prevention and treatment of pancreatitis.
    Type: Grant
    Filed: July 18, 1995
    Date of Patent: July 22, 1997
    Assignee: Senju Pharmaceutical Co., Ltd.
    Inventors: Kazumi Ogata, Takahiro Sakaue, Shinya Ogino, Sachiko Matsuura, Rie Nagao
  • Patent number: 5646176
    Abstract: The present invention concerns antitumor compounds. More particularly, the invention provides novel taxane derivatives, pharmaceutical compositions thereof, and their use as antitumor agents.
    Type: Grant
    Filed: May 19, 1995
    Date of Patent: July 8, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventors: Jerzy Golik, Dolatrai Vyas, John J. Wright, Henry Wong, John F. Kadow, John K. Thottathil, Wen-Sen Li, Murray A. Kaplan, Robert K. Perrone, Mark D. Wittman
  • Patent number: 5627173
    Abstract: Phosphonoacetic acid derivatives and their use for treating degenerative joint disorders Compounds of the formula I ##STR1## are suitable for producing pharmaceuticals for the treatment and prophylaxis of degenerative joint disorders, of rheumatic disorders accompanied by cartilage breakdown, such as rheumatoid arthritis, joint trauma and chondrolysis as a consequence of prolonged immobilization of the joint, of inflammations, septic shock, disorders with impaired leukocyte adhesion, disorders caused by an elevated concentration of tumor necrosis factor alpha, such as cachexia or Crohn's disease.
    Type: Grant
    Filed: January 23, 1996
    Date of Patent: May 6, 1997
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Rolf Graeve, Werner Thorwart, Ruth Raiss, Klaus U. Weithmann, Stefan M ullner
  • Patent number: 5622821
    Abstract: The invention provides lanthanide chelates capable of intense luminescence. The celates comprise a lanthanide chelator covalently joined to a coumarin-like or quinolone-like sensitizer. Exemplary sensitzers include 2- or 4-quinolones, 2- or 4-coumarins, or derivatives thereof e.g. carbostyril 124 (7-amino-4-methyl-2-quinolone), coumarin 120 (7-amino-4-methyl-2-coumarin), coumarin 124 (7-amino-4-(trifluoromethyl)-2-coumarin), aminomethyltrimethylpsoralen, etc.The chelates form high affinity complexes with lanthanides, such as terbium or europium, through chelator groups, such as DTPA. The chelates may be coupled to a wide variety of compounds to create specific labels, probes, diagnostic and/or therapeutic reagents, etc. The chelates find particular use in resonance energy transfer between chelate-lanthanide complexes and another luminescent agent, often a fluorescent non-metal based resonance energy acceptor.
    Type: Grant
    Filed: June 29, 1994
    Date of Patent: April 22, 1997
    Assignee: The Regents of the University of California
    Inventors: Paul R. Selvin, John Hearst
  • Patent number: 5616729
    Abstract: Triggerable dioxetanes with a fluorescent substituent bonded or tethered in the dioxetane so as to produce fluorescence from the group are described. The compounds are of the formula: ##STR1## wherein R.sub.1, R.sub.2 and R.sub.3 are carbon containing groups and wherein one of R.sub.1, R.sub.2 and R.sub.3 is a tethered fluorescent substitutent. The compounds are useful in immunoassays and in probes using enzymes or other chemicals for triggering the dioxetanes to produce light from the fluorescent molecule in the group as a signal.
    Type: Grant
    Filed: December 27, 1988
    Date of Patent: April 1, 1997
    Assignee: Board of Governors of Wayne State University
    Inventors: Arthur P. Schaap, Hashem Akhavan-Tafti
  • Patent number: 5612370
    Abstract: Compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof wherein a, b and d are all carbon atoms or one of a, b and d is a nitrogen atom or --N(O)-- and the others are carbon atoms; Y is a single bond, --CH.sub.2 --, --C(O)--, --O--, --S-- or --N(R.sup.8)--; and R.sup.1 to R.sup.7 are as defined herein. These compounds have potassium channel activating activity and are useful, therefore for example, as cardiovascular agents.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: March 18, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventor: Karnail S. Atwal
  • Patent number: 5612323
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: March 18, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventor: Raj N. Misra
  • Patent number: 5610122
    Abstract: The present invention relates to a new 3-aryl-4-hydroxy-.DELTA..sup.3 -dihydrofuranone derivatives of the general formula (I) ##STR1## in which the radicals A, B, G, X, Y, Z and n have the meaning given in the description, to a plurality of processes for their preparation, and to their use as pesticides.
    Type: Grant
    Filed: September 9, 1994
    Date of Patent: March 11, 1997
    Assignee: Bayer Aktiengesellschaft
    Inventors: Reiner Fischer, Thomas Bretschneider, Bernd-Wieland Kr uger, Hans-Joachim Santel, Markus Dollinger, Ulrike Wachendorff-Neumann, Christoph Erdelen
  • Patent number: 5603949
    Abstract: Use of a tocopherol phosphate, other than alpha-tocopherol phosphate, especially in its dl or d form, or one of its esters having general formula (I) in which: R' is hydrogen atom, an alkyl radical having from 1 to 4 carbon atoms, such as the methyl or ethyl radical in particular, R'O is a tocopheryl radical; R" is a hydrogen atom, an alkyl radical having from 1 to 4 carbon atoms, such as the methyl or ethyl radical in particular, or R"O is an oxyethylene chain, of formula (a) in which R.sub.4 and R.sub.5 are independently a hydrogen atom or a methyl radical, and n is an integer of 1 or over; R.sub.1, R.sub.2 and R.sub.3 are independently a hydrogen atom or a methyl radical, it being understood that R.sub.1, R.sub.2 and R.sub.3 cannot simultaneously be a methyl radical. A represents the groups (b), or (c).
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: February 18, 1997
    Assignee: LVMH Recherche
    Inventors: Alain Meybeck, Marc Dumas, Frederic Bonte, Christian Marechal