Cyclopentyl In Acid Moiety (e.g., Prostaglandins, Etc.) Patents (Class 560/121)
  • Patent number: 6066751
    Abstract: It has been surprisingly discovered that the disadvantages of the lengthy literature procedures to synthesize 13,14-dihydro prostaglandin A, E, and F derivatives can be overcome using a novel Methyl 7-(2-hydroxy-5-(2-(2-oxiranyl)ethyl)-4-(1,1,2,2 tetramethyl-1-silapropoxy)cyclopentyl) heptanoate intermediate, which can be synthesized from commercially available Methyl 7-[3-(R)-hydroxy-5-oxo-1-cyclopent-1-yl] heptanoate. This novel intermediate can be coupled with oxygen, carbon, sulfur, and nitrogen nucleophiles, in the presence of a base or a Lewis acid, in a ring-opening process to provide 13,14-dihydro prostaglandin A, E, and F derivatives.
    Type: Grant
    Filed: September 4, 1998
    Date of Patent: May 23, 2000
    Assignee: The Procter & Gamble Company
    Inventors: John August Wos, Jack Snyder Amburgey, Jr., Mitchell Anthony deLong, Yili Wang, Haiyan George Dai, Biswanath De
  • Patent number: 6043275
    Abstract: A 3,7-dithiaprostanoic acid derivative of the formula (I) ##STR1## (wherein, R.sup.1 is OH, C1.about.6 alkyloxy, NR.sup.6 R.sup.7 (R.sup.6, R.sup.7 are H, C1.about.6 alkyl.); R.sup.2 is H, OH; R.sup.3 is single bond, C1.about.6 alkylene; R.sup.4 is (i) C1.about.8 alkyl substituted by C1.about.6 alkyloxy, halogen etc., (ii) phenyloxy, C3.about.7 cycloalkyloxy, (iii) furyl, furyloxy, thienyl, thienyloxy, naphthyl, naphthyloxy, phthalanyl, phthalanyloxy, (iv) phenyl, phenyloxy, C3.about.7 cycloalkyl, C3.about.7 cycloalkyloxy substituted by C1.about.6 alkyl etc., (v) furyl, furyloxy, thienyl, thienyloxy, naphthyl, naphthyloxy, phthalanyl, phthalanyloxy substituted by C1.about.6 alkyl etc.; R.sup.5 is H, C1.about.6 alkyl.) can bind PGE.sub.2 receptor (particularly, EP4 subtype receptor) strongly. So, they are useful for the prevention and/or treatment of immunological diseases (autoimmune diseases, rejection after organ transplantation etc.
    Type: Grant
    Filed: April 8, 1999
    Date of Patent: March 28, 2000
    Assignee: Ono Pharmaceutical Co., Ltd.
    Inventors: Toru Maruyama, Shuichi Ohuchida
  • Patent number: 6025518
    Abstract: A substituted cyclopentene derivative of formula (V): whereinX.sup.1 is (.alpha.-OZ.sup.a, .beta.-H) or (.alpha.-H, .beta.-OZ.sup.a), X.sup.3 is (.alpha.-OZ.sup.d, .beta.-H), (.alpha.-H, .beta.-OZ.sup.d), or oxygen atom, each of Z.sup.a and Z.sup.d, which may be the same or different, is a hydrogen atom or a protective radical for a hydroxyl radical;U is a radical selected from the group consisting of CR.sup.1 HCH.sub.2, CR.sup.1 .dbd.CH and C.tbd.C,whereinR.sup.1 is a hydrogen atom, halogen atom, substituted silyl radical represented by SiR.sup.9 R.sup.10 R.sup.11 or substituted stannyl radical represented by SnR.sup.14 R.sup.15 R .sup.16,m is an integer of 0 to 6;X.sup.2 is CH.dbd.CH or C.tbd.C,p is an integer of 0 or 1, each of n and q is an integer of 0 to 5; andZ.sup.1 is a hydrogen atom, COOR.sup.y, CN, OH, OCOR.sup.2, CONR.sup.b R.sup.c or NR.sup.d R.sup.e.
    Type: Grant
    Filed: September 8, 1998
    Date of Patent: February 15, 2000
    Assignees: Nissan Chemical Industries, Ltd., Fumie SATO
    Inventor: Fumie Sato
  • Patent number: 5990138
    Abstract: The invention relates to 7-[5-hydroxy-2-(hydroxyhydrocarbyl or heteroatom-substituted hydroxy hydrocarbyl)-3-hydroxycyclopentyl(enyl)] heptanoic or heptenoic acids and derivatives of said acids, wherein one or more of said hydroxy groups are replaced by an ether group. The compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma.
    Type: Grant
    Filed: January 4, 1999
    Date of Patent: November 23, 1999
    Assignee: Allergan
    Inventor: Robert M. Burk
  • Patent number: 5990346
    Abstract: A prostaglandin having formula (I), (II), or (III): ##STR1## a process of production thereof, and inhibitors of cell migration caused by chemokines containing (I) or (II) as an active ingredient.
    Type: Grant
    Filed: February 26, 1997
    Date of Patent: November 23, 1999
    Assignee: Teijin Limited
    Inventors: Kenichiro Kataoka, Toru Minoshima, Tatsuki Shiota, Takaharu Tsutsumi, Takahiko Hada, Hiroko Tanaka, Takuya Morita, Noriaki Endo
  • Patent number: 5986095
    Abstract: A process is described for preparing a compound of the formula or the S-enantiomer thereof,wherein:R is alkyl, aryl, cycloalkyl, aralkyl, or cycloalkylalkyl,R.sup.1 is halogen;R.sup.2 is halogen, alkyl, cycloalkyl, aryl or ##STR1## wherein the process comprises treating the associated racemic alcohol with an acylatingagent ##STR2## (wherein L is a leaving group) and an enzyme or microorganism capable of enantioselective acylation. This process may also be used to isolate the unreacted R- or S-alcohol. The acylated product may be enantioselectively hydrolyzed with a lipase or lipase-supplying microorganism to the S- or R-alcohol. Compounds prepared by this invention are useful antipsychotic agents or useful intermediates therefor.
    Type: Grant
    Filed: January 6, 1992
    Date of Patent: November 16, 1999
    Assignee: E.R. Squibb & Sons, Inc.
    Inventors: Ronald L. Hanson, Ramesh N. Patel, Laszlo J. Szarka
  • Patent number: 5985920
    Abstract: A fluorine-containing prostaglandin derivative of the formula (1) (or a salt thereof) and a medicine containing it, particularly, a preventive or therapeutic medicine for an eye disease: ##STR1## wherein A is a vinylene group or the like, R.sup.1 is an aryloxyalkyl group or the like, R.sup.2 and R.sup.3 are hydrogen atoms or the like, and Z is OR.sup.4 (wherein OR.sup.4 is a hydrogen atom or an alkyl group) or the like.
    Type: Grant
    Filed: August 3, 1998
    Date of Patent: November 16, 1999
    Assignees: Asahi Glass Company Ltd., Santen Pharmaceutical Co., Ltd.
    Inventors: Eiichi Shirasawa, Masaaki Kageyama, Tadashi Nakajima, Takashi Nakano, Nobuaki Mori, Hideshi Sasakura, Yasushi Matsumura, Yoshitomi Morizawa
  • Patent number: 5962724
    Abstract: The present invention relates to a highly enantioselective process for the preparation of enantiomerically pure cyclopentane- and -pentene .beta.-amino acids of the general formula (I) ##STR1## in which A and L, A and D or E and L, D and E, R.sup.2, R.sup.3, T and R.sup.1 have the meaning given in the description.
    Type: Grant
    Filed: July 5, 1996
    Date of Patent: October 5, 1999
    Assignee: Bayer Aktiengesellschaft
    Inventors: Joachim Mittendorf, Hermann Arold, Peter Fey, Michael Matzke, Hans-Christian Militzer, Klaus-Helmut Mohrs
  • Patent number: 5935939
    Abstract: The present invention provides for stabilization of misoprostol in solid dispersions using amorphous excipients or excipients which have been converted to an amorphous state such as hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, cellulose acetate phthalate, cellulose acetate butyrate, hydroxyethyl cellulose, ethyl cellulose, polyvinyl alcohol, polyethylene glycol, starch, polypropylene, dextrans, dextrins, hydroxypropyl .beta.-cyclodextrin chitosan, co-(lactic/glycolic)copolymers, poly(orthoester), polyvinyl chloride, polyvinyl acetate, ethylene vinyl acetate, lectins, carbopols, silicon elastomers, cyclodextrins, polyacrylic polymers, maltodextrins, lactose, fructose, inositol, trehalose, maltose, and raffinose, (and other mono-, di- and tri- saccharides) and .alpha.-, .beta.- and .gamma.-cyclodextrins, and more preferably the excipients which are used are dextran, maltodextrin, hydroxypropyl .beta.-cyclodextrin and maltose.
    Type: Grant
    Filed: September 9, 1996
    Date of Patent: August 10, 1999
    Assignee: G. D. Searle & Co.
    Inventors: Tugrul T. Kararli, David Otto, Stanley C. Penzotti, Jr., James E. Truelove
  • Patent number: 5891910
    Abstract: The invention relates to 9-halogen-(Z) prostane derivatives of formula I ##STR1## in which ##STR2## Z represents the radicals Hal represents a chlorine or fluorine atom,R.sub.1 represents ##STR3## A represents a --CH.sub.2 --CH.sub.2 --, a trans--CH=CH or --C.ident.C, W represents a free or a functionally modified ##STR4## group, D and E together represent a direct bond orD represents a straight-chain alkylene group with 1-10 C atoms, a branched-chain alkylene group with 2-10 C atoms or an annular alkylene group with 3-10 C atoms, which optionally can be substituted by fluorine atoms, andE represents an oxygen or sulfur atom, a direct bond, a C.ident.C bond or a --CR.sub.6 =CR.sub.7 group, and R.sub.6 and R.sub.7 are different and mean a hydrogen atom, a chlorine atom or a C.sub.1 -C.sub.4 alkyl group,R.sub.4 represents a free or functionally modified hydroxy,R.sub.5 means a hydrogen atom, an alkyl, a halogen-substituted alkyl, a cycloalkyl or an optionally substituted aryl or a heterocyclic group.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: April 6, 1999
    Assignee: Schering Aktiengesellschaft
    Inventors: Bernd Buchmann, Werner Skuballa, Helmut Vorbrueggen, Bernd Raduechel, Olaf Loge, Walter Elger, Claus-Steffen Stuerzebecher, Karl-Heinz Thierauch
  • Patent number: 5892099
    Abstract: A 3,7-dithiaprostanoic acid derivative of the formula (I) ##STR1## (wherein R.sup.1 is OH, C1-4 alkoxy, NR.sup.6 R.sup.7 (wherein R.sup.6, R.sup.7 are H, C1-4);R.sup.2 is H, OH; R.sup.3 is (i)alkyl, alkenyl, alkynyl (ii) phenyl, cycloalkyl (iii) alkyl, alkenyl, alkynyl substituted by phenyl, cycloalkyl (when R.sup.2 is H, alkyl, alkenyl, alkynyl in (i) or (iii) may be substituted by OH) possesses a binding activity for PGE.sub.2 receptor (especially for EP4). Therefore they are useful for the treatment and/or prevention of immunologic diseases (autoimmune diseases, immunological deficiency diseases, organ transplantation etc.), asthma, abnormal bone formation, neuronal cell death, liver damage, nephritis, hypertension, myocardiac ischemia etc.
    Type: Grant
    Filed: January 27, 1998
    Date of Patent: April 6, 1999
    Assignee: Ono Pharmaceutical Co., Ltd.
    Inventors: Toru Maruyama, Shuichi Ohuchida
  • Patent number: 5886034
    Abstract: The novel 13,14-dihydro-15-keto prostaglandins E of the invention have remarkable preventive effects against ulcers. Further, the novel 13,14-dihydro-15-keto-prostaglandins E of the invention have an advatage that they have none of side effects which prostaglandin E intrinsically has, or can remarakably reduce such effects of the prostaglandin E. Therefore, the novel 13, 14-dihydro-15-keto prostaglandins E of the invention are effective for animal and human use for treatment and prevention of ulcers, such as duodenal ulcer and gastric ulcer.
    Type: Grant
    Filed: March 10, 1995
    Date of Patent: March 23, 1999
    Assignee: Kabushiki Kaisha Ueno Seiyaku Kenkyujo
    Inventors: Ryuzo Ueno, Ryuji Ueno, Ichie Kato, Tomio Oda
  • Patent number: 5874600
    Abstract: A catalyst of ruthenium (II) which includes bidentate phosphine ligands. The catalyst is obtainable by a process which includes the steps of treating equimolar amounts of an appropriate Ru(II) complex and a bidentate diphosphine ligand with an acid of formula HX, wherein X is a non-coordinating anion. The acid is used in a ratio which does not exceed 2 molar equivalents per mole of Ru(II) complex and the treatment is carried out in a non-coordinating or weakly coordinating solvent and under an inert atmosphere. This catalyst is useful for the preparation of the preferred isomer of HEDIONE, having the (+)-(1R)-cis-configuration.
    Type: Grant
    Filed: July 10, 1997
    Date of Patent: February 23, 1999
    Assignee: Firmenich SA
    Inventors: Valentin Rautenstrauch, Koenraad P. M. Vanhessche, Jean-Pierre Genet, Jean-Yves Lenoir
  • Patent number: 5859283
    Abstract: 4-Substituted isoxazole derivatives of formula I: ##STR1## wherein R, R.sup.1, R.sup.2, Q and n have the meanings defined in the description, which possess valuable herbicidal properties and intermediates useful in their preparation.
    Type: Grant
    Filed: February 11, 1998
    Date of Patent: January 12, 1999
    Assignee: Rhone-Poulenc Agriculture Limited
    Inventor: Susan Mary Cramp
  • Patent number: 5827883
    Abstract: A method of using vitamin D derivatives of the formula ##STR1## wherein X is .dbd.CH.sub.2 or H,H;Y is a moiety--CH(CH.sub.3)--(A).sub.n --C(O)--OR.sup.1 (a)--CH(CH.sub.3)--CH.sub.2 --O--C(O)--R.sup.2 (b)or--C(O)--OR.sup.1 (c);A is --CH.dbd.CH-- or CH.sub.2 --CH.sub.2 --R.sup.1 is lower alkyl, cycloalkyl, cycloalkylmethyl, --CH.sub.2 R.sup.3 or --CH.sub.2 --CH.sub.2 R.sup.3 ;R.sup.2 is lower alkyl, cycloalkyl or R.sup.3 ;R.sup.3 is hydroxy-lower alkyl, hydroxy-cycloalkyl or trifluoromethyl-hydroxy-lower-alkyl;n is 0 or 1;and the dotted bond in the five membered ring is optional;in the treatment of dermatological conditions, in particular keratinization disorders such as psoriasis, as well as acne and photodamaged skin, is described.Vitamin D derivatives of the formula I above, wherein X, Y, A, R.sup.1, R.sup.2, R.sup.3 and n are as set forth above; with the proviso that X is H,H when Y is --CH(CH.sub.3)--CH.sub.2 --OC(O)--C(OH)(CH.sub.3).sub.
    Type: Grant
    Filed: July 21, 1997
    Date of Patent: October 27, 1998
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Pierre Barbier, Marc Muller, Josef Stadlwieser
  • Patent number: 5817694
    Abstract: Analogs of the prostaglandin PGE.sub.1 are disclosed. These compounds exhibit uterotonic properties, enhancing the response to PGF.sub.2 .alpha. in isolated rat uteri. The compounds also exhibit other pharmacological properties, as inhibitors of gastric acid secretion, hypotensives, and bronchodilators. Processes for making the analogs, useful intermediates, and pharmaceutical preparations are also presented.
    Type: Grant
    Filed: June 4, 1993
    Date of Patent: October 6, 1998
    Assignee: New Pharma International Corp.
    Inventors: Carlos Alberto Genaro Mammarella, Carlos Alberto Buschi, Silvia Susana Giarcovich
  • Patent number: 5807892
    Abstract: Certain prostaglandin analogues are useful in the treatment of glaucoma and ocular hypertension. Also disclosed are ophthalmic, pharmaceutical compositions comprising such prostaglandin analogues.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: September 15, 1998
    Assignee: Alcon Laboratories, Inc.
    Inventors: Peter G. Klimko, Robert D. Selliah, Thomas R. Dean, Mark R. Hellberg, John E. Bishop
  • Patent number: 5783602
    Abstract: The invention relates to leukotriene-B.sub.4 derivatives of general formula I, ##STR1## in which R.sub.1 represents CH.sub.2 OH, CH.sub.3, CF.sub.3 COOR.sub.4 CONR.sub.5 R.sub.6, andR.sub.3 symbolizes H; C.sub.1 -C.sub.14 alkyl, C.sub.3 -C.sub.10 cycloalkyl optionally substituted singly or multiply; C.sub.6 -C.sub.10 aryl radicals, independently of one another, optionally substituted singly or multiply by halogen, phenyl, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, fluoromethyl, chloromethyl, trifluoromethyl, carbonyl, carboxyl or hydroxy; or a 5- to 6-membered aromatic heterocyclic ring with at least 1 heteroatom,X and Y mean a direct bond, whereby the resulting olefin can be E- or Z-configured or X represents a fluorine atom in .alpha.- or .beta.-position, and Y means a hydrogen atom in .beta.-position.
    Type: Grant
    Filed: December 4, 1996
    Date of Patent: July 21, 1998
    Assignee: Schering Aktiengesellschaft
    Inventors: Werner Skuballa, Bernd Buchmann, Josef Heindl, Wolfgang Frohlich, Roland Ekerdt, Claudia Giesen
  • Patent number: 5770759
    Abstract: The present invention provides new compounds, 13,14-dihydro-15-keto-PGFs, and vassopressors containing them, which raise blood pressure without substantial ephemeral depression of blood pressure, trachea or enteron contraction effect inherent in usual PGFs.
    Type: Grant
    Filed: August 23, 1996
    Date of Patent: June 23, 1998
    Assignee: R-Tech Ueno, Ltd.
    Inventors: Ryuzo Ueno, Ryuji Ueno, Tomio Oda
  • Patent number: 5760277
    Abstract: The cycloaliphatic ketones of formula ##STR1## having two conjugated double bonds in positions 1 and 3, or 2 and 4, such as indicated by the dotted lines, and wherein R defines a C.sub.1 to C.sub.
    Type: Grant
    Filed: January 15, 1997
    Date of Patent: June 2, 1998
    Assignee: Firmenich SA
    Inventors: Ferdinand Naef, Rene Decorzant
  • Patent number: 5756818
    Abstract: The invention relates to 9-chloro-prostaglandin derivatives of formula I ##STR1## in which X means oxygen or CH.sub.2,R.sup.1 means hydrogen or straight-chain or branched alkyl with 1-6 C atoms andA means trans-CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --,as well as their salts with physiologically compatible bases, if R.sup.1 represents hydrogen, and their clathrates with .alpha.-, .beta.- or .gamma.-cyclodextrin, process for their production and their pharmaceutical use.
    Type: Grant
    Filed: May 29, 1996
    Date of Patent: May 26, 1998
    Assignee: Schering Aktiengesellschaft
    Inventors: Bernd Buchmann, Werner Skuballa
  • Patent number: 5739161
    Abstract: The object of the present invention is to provide a pharmaceutical composition for treatment of hepato.biliary disease reduced in side effect such as diarrhea, which comprises 16,16-difluoro-15-keto-PGs having at least one methyl group or ethyl group on the carbon atom at the 17- or 18-position or adjacent to the terminal methyl group of .omega.-chain as an essential component.
    Type: Grant
    Filed: February 12, 1997
    Date of Patent: April 14, 1998
    Assignee: R-Tech Ueno, Ltd.
    Inventor: Ryuji Ueno
  • Patent number: 5736274
    Abstract: A polymer containing a recurring unit of a conjugated N-fluoropyridinium salt and an active material for a positive electrode, an electrolyte, a battery material for the positive electrode and a battery which use such a polymer. That polymer provides a battery material and a primary battery or a secondary battery which have high electromotive force, high energy density, high environmental acceptability, a low internal resistance in charging and discharging and strong recoverability of the electromotive force, and can be useful as a fluorinating agent.
    Type: Grant
    Filed: April 18, 1997
    Date of Patent: April 7, 1998
    Assignee: Daikin Industries, Ltd.
    Inventors: Teruo Umemoto, Kenji Adachi, Ginjiro Tomizawa, Sumi Ishihara, Masayuki Nagayoshi
  • Patent number: 5731452
    Abstract: 7-thiaprostaglandins having the formula (I) which inhibit cell migration induced by monocyte chemoattractant protein MCP-1/MCAF and other chemokines and can serve as drugs for the treatment of atherosclerosis, diabetic angiopathy, and other disorders, their enantiomers, mixtures of the same, and methods of production thereof.
    Type: Grant
    Filed: September 18, 1995
    Date of Patent: March 24, 1998
    Assignee: Teijin Limited
    Inventors: Toru Minoshima, Kenichiro Kataoka, Hiroko Tanaka, Koji Ishii, Noriaki Endo
  • Patent number: 5698590
    Abstract: Prostaglandin E.sub.1 ester derivatives of the formula (I): ##STR1## wherein the R' groups are the same as each other and are C4-12 alkyl; or cyclodextrin clathrates thereof, liposome formulations containing them, and pharmaceutical compositions containing them, as active ingredient.The compounds of formula (I) have the effect of increasing blood flow and are useful for the prevention and/or treatment of peripheral circulatory disorder, decubitus, or skin ulcers, or for the maintenance of blood flow.
    Type: Grant
    Filed: August 22, 1996
    Date of Patent: December 16, 1997
    Assignee: Ono Pharmaceutical Co., Ltd.
    Inventors: Akio Nishiura, Takuya Seko, Ryoji Matsumoto, Shin-ichi Hamano
  • Patent number: 5690957
    Abstract: Prostaglandin E, ester derivatives of the formula (I): ##STR1## wherein R is (i) --CH.sub.2 CH.sub.2 --O--CO--R.sup.1(ii) --CH.sub.2 CH.sub.2 --O--CO--CH.sub.2 --O--R.sup.2, andR.sup.1 and R.sup.2 each independently is C10-20 alkyl;and cyclodextrin clathrates thereof, liposome formulations containing them, and pharmaceutical compositions containing them as active ingredient.The compounds of formula (I) have the effect of increasing blood flow and are useful for the prevention and/or treatment of peripheral circulatory disorder, decubitus, or skin ulcers, or for the maintenance of blood flow.
    Type: Grant
    Filed: August 14, 1996
    Date of Patent: November 25, 1997
    Assignee: Ono Pharmaceutical Co., Ltd.
    Inventors: Akio Nishiura, Takuya Seko, Ryoji Matsumoto, Shin-ichi Hamano
  • Patent number: 5684177
    Abstract: In a process for making synthetic prostaglandin-type compounds such as misoprostol, organo metallic cuprate complexes capable of reacting with cyclopentenones are prepared by reaction of an alkyl lithium compound with a cuprous halide, followed by reaction of the resulting complex with a vinyl stannane, using an excess of alkyl lithium in the initial reaction and maintaining the excess present during the formation of the organo metallic cuprate complex.
    Type: Grant
    Filed: May 17, 1996
    Date of Patent: November 4, 1997
    Assignee: Torcan Chemical Ltd.
    Inventors: Yee-Fung Lu, Raymond So, Dan To, Casimir G. Antczak
  • Patent number: 5663417
    Abstract: (1) Prostaglandin (PG) E.sub.2 antagonist or agonist containing carbocyclic sulfonamides represented by the compound of the formula (I): ##STR1## cyclodextrin clathrates thereof, non-toxic salts thereof as active ingredient, (2) carbocyclic sulfonamides represented by the compound of the formula (II): ##STR2## cyclodextrin clathrates thereof, non-toxic salts thereof, (3) process for the preparation of the compound represented by the compound of the formula (II) described hereinbefore, (4) PGE.sub.2 antagonist or agonist containing the compound represented by the compound of the formula (II) as active ingredient.The compounds represented by the compounds of the formula (I) and (II) can be adapted to medicines which possess an inhibitory effect of uterine contraction, an analgetic action, an inhibitory effect of digestive peristalsis, a sleep-inducing effect as PGE.sub.
    Type: Grant
    Filed: January 27, 1994
    Date of Patent: September 2, 1997
    Assignee: Ono Pharmaceutical Co., Ltd.
    Inventors: Nobuyuki Hamanaka, Tsumoru Miyamoto
  • Patent number: 5639899
    Abstract: Object: To provide novel prostaglandin E.sub.1 analogues which have more excellent pharmaceutical effects, longer duration of the effects and less side-effects than the prior art prostaglandin E.sub.1 's.Constitution: A PGE.sub.1 analogue represented by the formula: ##STR1## (wherein A is a vinylene group or an ethynylene group, R.sup.1 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an allyl group, R.sup.2 is a branched aliphatic hydrocarbon group having 5 to 10 carbon atoms), or a salt thereof.
    Type: Grant
    Filed: October 19, 1993
    Date of Patent: June 17, 1997
    Assignees: Taisho Pharmaceutical Co., Ltd., Fumie Sato
    Inventors: Fumie Sato, Takehiro Amano, Kazuya Kameo, Tohru Tanami, Masaru Mutoh, Naoya Ono, Jun Goto
  • Patent number: 5625083
    Abstract: The present invention relates to novel dinitroglycerol esters of fatty acids, hydroxy fatty acids and prostaglandins, and methods for producing them. Dinitroglycerol esters provided by this invention have an improved biological specificity and/or a greater specific activity than the parent compound. The novel prostanoids produced herein may be used as vasodilators, antihypertensive cardiovascular agents, bronchodilators, and they may have uses in obstetrics and gynecology. The dinitroglycerol esters of fatty acids and hydroxy fatty acids may be useful as platelet antiaggregating agents.
    Type: Grant
    Filed: June 2, 1995
    Date of Patent: April 29, 1997
    Inventors: Vladimir V. Bezuglov, Igor V. Serkov
  • Patent number: 5625067
    Abstract: The invention relates to cyclopentane ether derivatives of Formula I ##STR1## their salts with physiologically compatible bases, as well as the .alpha.-, .beta.- or .gamma.-cyclodextrin clathrates, and also the liposome-encapsulated compounds of Formula I, processes for their production, and their pharmaceutical usage.
    Type: Grant
    Filed: December 14, 1994
    Date of Patent: April 29, 1997
    Assignee: Schering Aktiengesellschaft
    Inventors: Hartmut Rehwinkel, Ulrich Klar, Helmut Vorbruggen, Karl-Heinz Thierauch, Peter Verhallen
  • Patent number: 5618970
    Abstract: Compounds of formula ##STR1## where R is 5-indanyl or a carboxylic acid protecting group, or an amine salt thereof, are prepared by hydrogenating an (E)-allylic ether of formula ##STR2## in the presence of a stereoselective rhodium or ruthenium biphosphine catalyst and a protic solvent.
    Type: Grant
    Filed: March 7, 1996
    Date of Patent: April 8, 1997
    Assignee: Pfizer Inc.
    Inventor: Stephen Challenger
  • Patent number: 5618959
    Abstract: A process for synthesizing prostaglandin E.sub.1, E.sub.2 and derivatives thereof is provided. The process is a "one-pot" method in which 2-furyllithium, copper cyanide, a lower alkyllithium reagent and either an (E)-alkenylstannane or a halogenide are combined with cyclopentenone (II) ##STR1## in which A, R.sup.6 and R.sup.7 are as defined herein. The reaction gives rise to the desired prostaglandin product in yields of 80% or higher.
    Type: Grant
    Filed: March 10, 1995
    Date of Patent: April 8, 1997
    Assignee: Vivus Incorporated
    Inventors: Miroslav Trampota, Bohumil Zak
  • Patent number: 5610188
    Abstract: Compounds of the formula ##STR1## wherein the variables are defined in the specification. The compounds and their salts are soft anticholinergic/antisecretory agents especially useful as mydriatics and as antiperspirants.
    Type: Grant
    Filed: December 30, 1994
    Date of Patent: March 11, 1997
    Assignee: University of Florida
    Inventors: Richard H. Hammer, Nicholas S. Bodor
  • Patent number: 5599838
    Abstract: A prostaglandin derivative represented by the formula: ##STR1## wherein X is halogen atom R.sup.1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R.sup.2 is a cycloalkyl group having 3 to 10 carbon atoms, a cycloalkylmethyl group having 4 to 10 carbon atoms or a cycloalkylethyl group having 5 to 12 carbon atoms, or a salt thereof, which has an excellent lowering action of intraocular pressure and improving actions of renal diseases, ischemic heart diseases and heart failure.
    Type: Grant
    Filed: February 23, 1996
    Date of Patent: February 4, 1997
    Assignees: Taisho Pharmaceutical Co., Ltd., Fumie Sato
    Inventors: Fumie Sato, Takehiro Amano, Kazuya Kameo, Tohru Tanami, Masaru Mutoh, Naoya Ono, Jun Goto
  • Patent number: 5599837
    Abstract: The present invention relates to a 15-deoxyprostaglandin derivative of the formula (I): ##STR1## in which ##STR2## is a 5 membered ring which is selected from a group consisting of ##STR3## R.sup.1 is hydrogen or lower alkyl; R.sup.2 is C.sub.6 -C.sub.12 alkyl, C.sub.6 -C.sub.12 alkenyl or C.sub.6 -C.sub.12 alkadienyl;provided that the compound of the following formula is excluded: ##STR4## wherein R' is hydrogen or methyl; or pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical formulation comprising a 15-deoxyprostaglandin derivative as an active ingredient, which is useful as an intraocular pressure reducing agent.
    Type: Grant
    Filed: February 28, 1995
    Date of Patent: February 4, 1997
    Assignee: Shionogi & Co., Ltd.
    Inventors: Morio Kishi, Kimio Takahashi, Kenji Kawada, Yasumasa Goh
  • Patent number: 5591887
    Abstract: The present invention provides new compounds, 13,14-dihydro-15-keto-PGFs, and vassopressors containing them, which raise blood pressure without substantial ephemeral depression of blood pressure, trachea or enteron contraction effect inherent in usual PGFs.
    Type: Grant
    Filed: December 22, 1994
    Date of Patent: January 7, 1997
    Assignee: R-Tech Ueno, Ltd.
    Inventors: Ryuzo Ueno, Ryuji Ueno
  • Patent number: 5583158
    Abstract: A prostaglandin E.sub.1 analogue represented by formula ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl group; and X is an oxygen atom and R.sup.2 represents ##STR2## or X is a sulfur atom and R.sup.2 represents ##STR3## The compound has a strong and prolonged inhibitory action for platelet aggregation and is useful for treatment of various thrombotic diseases including peripheral circulatory disturbance.
    Type: Grant
    Filed: April 19, 1995
    Date of Patent: December 10, 1996
    Assignee: Taisho Pharmaceutical Co., Ltd.
    Inventors: Fumie Sato, Takehiro Amano, Kazuya Kameo, Tohru Tanami, Masaru Mutoh, Naoya Ono, Jun Goto
  • Patent number: 5571936
    Abstract: Intermediate compounds represented as formula (I) useful for the synthesis of 16-phenoxy-prostatrienoic acid derivatives and a preparing method thereof are disclosed. ##STR1## wherein R is tetrahydropyranyl, tetrahydrofuranyl, 2-ethoxyethyl, 3-t-butyldimethylsilyl triisopropylsilyl or triethylsilyl group; R.sup.1 and R.sup.2 are independently hydrogen or ester-forming group; P is hydrogen, trimethylsilyl or tri-n-butyltin; and wavy line means epistereoisomeric mixture.
    Type: Grant
    Filed: September 30, 1994
    Date of Patent: November 5, 1996
    Assignee: Korea Institute of Science and Technology
    Inventors: Hokoon Park, Sun Ho Jung, Yong Sup Lee, Ki Hong Nam
  • Patent number: 5569778
    Abstract: A process for preparing a fluorine-containing dicarbonyl compound of the formula: R.sup.1 COCFR.sup.2 COR.sup.3 in which R.sup.1 is a hydrogen atom, or a substituted or unsubstituted alkyl or aryl group; R.sup.2 is a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl or aryl group; and R.sup.3 is a hydrogen atom, or a substituted or unsubstituted alkyl, aryl, alkoxy or aryloxy group, provided that at least two of R.sup.1, R.sup.2 and R.sup.3 may together form a part of a cyclic structure with or without a hetero atom, by reacting a dicarbonyl compound of the formula: R.sup.1 COCHR.sup.2 COR.sup.3 in which R.sup.1, R.sup.2 and R.sup.3 are the same as defined above with fluorine (F.sub.2) in at least one solvent selected from the group consisting of halogenated hydrocarbons having 1 to 5 carbon atoms and nitrile compounds, or in a solvent in the presence of a salt, or an acid having pKa of 6 or less.
    Type: Grant
    Filed: April 28, 1995
    Date of Patent: October 29, 1996
    Assignee: Daikin Industries Ltd.
    Inventors: Teruo Umemoto, Ginjiro Tomizawa
  • Patent number: 5545665
    Abstract: The invention relates to 7-[5-hydroxy-2-(hydroxyhydrocarbyl or heteroatom-substituted hydroxy hydrocarbyl)-3-hydroxycyclopentyl(enyl)] heptanoic or heptenoic acids and derivatives of said acids, wherein one or more of said hydroxy groups are replaced by an ether group. The compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma.
    Type: Grant
    Filed: December 28, 1993
    Date of Patent: August 13, 1996
    Assignee: Allergan
    Inventor: Robert M. Burk
  • Patent number: 5543076
    Abstract: The chiral group of the formula ##STR1## is used as a constituent of liquid-crystalline compounds.
    Type: Grant
    Filed: September 16, 1994
    Date of Patent: August 6, 1996
    Assignee: BASF Aktiengesellschaft
    Inventors: Karl Siemensmeyer, Carsten Tschierske, Fritz Theil, Detley Joachimi
  • Patent number: 5534547
    Abstract: The present invention provides novel prostaglandins D, that is, 13,14-dihydro-15-keto-PGDs, whieh have an excellent sedative and sleep-inducing activity, and so they are useful for tranquilizer and/or soporifics.
    Type: Grant
    Filed: September 23, 1994
    Date of Patent: July 9, 1996
    Assignee: Kabushiki Kaisha Ueno Seiyaku Oyo Kenkyujo
    Inventors: Ryuzo Ueno, Ryuji Ueno, Ichie Kato, Tomio Oda
  • Patent number: 5523461
    Abstract: The present invention provides a method of stabilizing a prostanoic acid compound, wherein the prostanoic acid compound having at least one oxo group on the .omega. chain are stored in a hydrous condition.
    Type: Grant
    Filed: February 25, 1994
    Date of Patent: June 4, 1996
    Assignee: R-Tech Ueno, Ltd.
    Inventors: Ryuji Ueno, Ryu Hirata
  • Patent number: 5516796
    Abstract: Thiosubstituted prostaglandin derivatives and related compounds having the general structure ##STR1## useful as intraocular pressure reducing agents; pharmaceutical compositions containing such compounds; and methods of treatment using such compositions are disclosed.
    Type: Grant
    Filed: March 24, 1994
    Date of Patent: May 14, 1996
    Assignee: Kabi Pharmacia AB
    Inventors: Johan W. Stjernschantz, Bahram Resul, Laszlo Z. Bito
  • Patent number: 5491254
    Abstract: ObjectNovel PG derivatives having an excellent platelet aggregation inhibition activity are provided.ConstructionProstaglandin derivatives represented by formula: ##STR1## and salts thereof.
    Type: Grant
    Filed: January 19, 1995
    Date of Patent: February 13, 1996
    Assignees: Taisho Pharmaceutical Co., Ltd., Fumie Sato
    Inventors: Fumie Sato, Takehiro Amano, Kazuya Kameo, Tohru Tanami, Masaru Mutoh, Naoya Ono, Jun Goto
  • Patent number: 5476872
    Abstract: Compounds of the formula ##STR1## where the hatched lines indicate alpha (.alpha.) configuration, a solid triangle is used to indicate beta (.beta.) configuration, lines on both sides of a double bond indicate cis (Z) configuration, and lines on opposite sides of the double bond indicate trans (E) configuration; R.sub.1 is alkyl of 1-10 carbons, C.sub.1 -C.sub.10 alkylphenyl, phenyl-C.sub.1 -C.sub.10 alkyl, or alkenyl of 2 to 10 carbons and having 1 to 3 double bonds; R.sub.2 is Z--OR.sub.3, Z--OCOR.sub.3, Z--OCONHR.sub.3, Z--OCOOR.sub.3, Z--NR.sub.4 R.sub.5, Z--NR.sub.4 COR.sub.3, Z--NR.sub.4 SO.sub.2 R.sub.3, Z--COOR.sub.3, Z--CONR.sub.4 R.sub.5, Z--CHO; Z is (CH.sub.2).sub.n where n is 1-6, or Z is an alkenyl group having 2 to 6 carbons and 1 or 2 double bonds, R.sub.3 is H, alkyl of 1-6 carbons, alkenyl of 2 to 6 carbons or phenyl, R.sub.4 and R.sub.5 independently are H or alkyl of 1 to 6 carbons, have ocular hypotensive activity.
    Type: Grant
    Filed: October 18, 1993
    Date of Patent: December 19, 1995
    Assignee: Allergan, Inc.
    Inventors: Michael E. Garst, Elizabeth T. Syage, Michael B. Roof, David F. Woodward, Ming Fai Chan
  • Patent number: 5457131
    Abstract: The present invention relates to cyclopentane heptanoic or cyclopentane heptenoic acid, 2-hydrocarbyl sulfonamidomethyl, and derivatives thereof, useful as therapeutic agents. In particular, the therapeutic agents of this invention are useful as ocular hypotensives.
    Type: Grant
    Filed: August 18, 1994
    Date of Patent: October 10, 1995
    Assignee: Allergan, Inc.
    Inventor: Steven W. Andrews
  • Patent number: 5453464
    Abstract: This invention provides the use and preparation of certain 2,2'-diacetyl-bisacetoacetates and bis(beta-ketoesters). These compounds are useful in coating formulations as crosslinkers in conjunction with polyester, acrylic and/or other hydroxylated resins to provide coatings that cure at about 100.degree. and 175.degree. C. Certain combinations of these crosslinkers and resins cure at unusually low temperatures and provide films with good combinations of flexibility, hardness and adhesion.
    Type: Grant
    Filed: April 28, 1994
    Date of Patent: September 26, 1995
    Assignee: Eastman Chemical Company
    Inventors: J. Stewart Witzeman, Allen L. Crain
  • Patent number: 5449815
    Abstract: Object: To provide novel prostaglandin E.sub.1 analogues which have more excellent pharmaceutical effects, longer duration of the effects and less side-effects than the prior art prostaglandin E.sub.1 's.Constitution: A PGE.sub.1 analogue represented by the formula: ##STR1## (wherein R.sup.1 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an allyl group, and R.sup.2 is an alkyl group having 3 to 6 carbon atoms, an alkenyl group having 3 to 6 carbon atoms), or a salt thereof.
    Type: Grant
    Filed: October 19, 1993
    Date of Patent: September 12, 1995
    Assignees: Taisho Pharmaceutical Co., Ltd., Fumie Sato
    Inventors: Fumie Sato, Takehiro Amano, Kazuya Kameo, Tohru Tanami, Masaru Mutoh, Naoya Ono, Jun Goto