Plural Isoquinoline Ring Systems Attached Directly Or Indirectly To Each Other By Nonionic Bonding Patents (Class 514/308)
  • Patent number: 6048860
    Abstract: Anti-pruritic pharmaceutical formulations containing kappa agonist compounds and methods of prevention or treatment of pruritus in a mammal with the anti-pruritic formulations.
    Type: Grant
    Filed: October 4, 1999
    Date of Patent: April 11, 2000
    Assignee: Adolor Corporation
    Inventors: John J. Farrar, An-Chih Chang, Virendra Kumar, Wei Yuan Zhang, Alan Cowan
  • Patent number: 6034097
    Abstract: The present invention is directed to compounds that act as analgesics and that have the structure of formula (I): ##STR1## wherein; Z is ##STR2## wherein, n is 1 or 2, and R.sub.0 is C.sub.6-12 aryl or C.sub.7-8 aralkyl; orR.sub.1 is selected from the group consisting of hydrogen; --NH--C.sub.1-6 alkyl; C.sub.1-6 alkyl; C.sub.6-12 aryl; C.sub.7-18 aralkyl; arginyl; and R.sub.30 NHC(.dbd.NH)--, wherein R.sub.30 is hydrogen, C.sub.6-12 aryl, C.sub.7-18 aralkyl, or C.sub.1-6 alkyl;R.sub.2 is hydrogen; C.sub.1-6 alkyl; or OH;R.sub.3 is C.sub.6-12 aryl; C.sub.7-18 aralkyl; --CH.sub.2 --C.sub.6 H.sub.2 R.sub.8 R.sub.9 ;or --CH.sub.2 --OHC.sub.6 HR.sub.8 R.sub.9, wherein each of R.sub.8 and R.sub.9 is independently, or hydrogen;R.sub.4 C.sub.6-12 aryl; C.sub.7-18 aralkyl; C.sub.1-12 alkyl; or a substituted or unsubstituted cyclohexyl;R.sub.5 is C.sub.1-6 alkyl; hydrogen; OH; halogen; SH; NO.sub.2 ; NH.sub.2 ; --NH--C.sub.1-6 alkyl; NH.sub.2 C (.dbd.NH--; NH.sub.2 C (.dbd.NH)--NH--; COOR.sub.31, wherein, R.sub.
    Type: Grant
    Filed: October 6, 1997
    Date of Patent: March 7, 2000
    Assignee: Astra AB
    Inventors: John DiMaio, Wuyi Wang
  • Patent number: 5994323
    Abstract: A pharmaceutical composition is disclosed that comprises clioquinol, vitamin B.sub.12, and, optionally, pharmaceutical acceptable carriers and/or excipients. The use of the pharmaceutical composition removes or alleviates the side effects of clioquinol.
    Type: Grant
    Filed: February 13, 1998
    Date of Patent: November 30, 1999
    Assignee: P.N. Gerolymatos S.A.
    Inventor: Panayotis N. Gerolymatos
  • Patent number: 5965730
    Abstract: A pyridine derivative of the formula (I): ##STR1## wherein A is group of the following formulae: ##STR2## (R.sup.1 and R.sup.2 are each H, or protected or unprotected OH, R.sup.31, R.sup.41 and R.sup.42 are protected or unprotected hydroxymethyl, R.sup.32 is H, lower alkyl, or protected or unprotected hydroxymethyl, R.sup.33 is substituted or unsubstituted lower alkyl, and the dotted line means the presence or absence of a double bond), R.sup.5 and R.sup.6 are H, or protected or unprotected amino, or both combine together with the adjacent nitrogen to form substituted or unsubstituted heterocycle, or a pharmaceutically acceptable salt thereof, these compounds showing excellent bronchoconstriction inhibitory activity and/or anti-inflammatory activity of airway, and being useful in the prophylaxis or treatment of asthma.
    Type: Grant
    Filed: December 4, 1997
    Date of Patent: October 12, 1999
    Assignee: Tanabe Seiyaku Co., Ltd.
    Inventors: Tatsuzo Ukita, Masakatsu Sugahara, Katsuo Ikezawa, Hideo Kikkawa, Kazuaki Naito
  • Patent number: 5905086
    Abstract: N-(2-Hydroxyethyl)nicotinamide nitrate or its salt prevents or ameliorates anxiety neurosis or panic disorder, or the following anxiety. This compound or its salt has few side effects and exhibits immediate action.
    Type: Grant
    Filed: February 13, 1998
    Date of Patent: May 18, 1999
    Assignee: Chugai Seiyaku Kabushiki Kaisha
    Inventor: Toshiro Miura
  • Patent number: 5863929
    Abstract: This invention relates to a compound of the Formula IX--C(O)--Y--G--R I(wherein X, Y, G and R have the values defined in the description), or a pharmaceutically acceptable salt thereof, processes and intermediates for the preparation of such a compound or salt, pharmaceutical compositions comprising such a compound or salt and methods of their use as thrombin inhibitors, coagulation inhibitors and agents for the treatment of thromboembolic disorders.
    Type: Grant
    Filed: June 20, 1997
    Date of Patent: January 26, 1999
    Assignee: Eli Lilly and Company
    Inventors: Valentine Joseph Klimkowski, Aaron Leigh Schacht, Michael Robert Wiley
  • Patent number: 5744472
    Abstract: Disclosed are compounds of the formula ##STR1## or the pharmaceutically acceptable salts thereof wherein the 6-membered A ring may be optionally substituted with up to four groups independently selected from halogen, hydroxy, lower alkyl, or lower alkoxy;Ar represents optionally substituted aryl or heteroarylZ represents carbon or nitrogen provided thatwhere Z is carbon, R.sub.11 represents hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy, or phenyl optionally substituted with one or two groups selected from hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy; andwhere Z is nitrogen, R.sub.11 represents an electron pair;R.sub.5 is hydrogen or lower alkyl;L and m represent integers;n is 0, or an integer;R.sub.12 and R.sub.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: April 28, 1998
    Assignee: Neurogen Corporation
    Inventors: Xiao-shu He, Brian de Costa, Jan W. F. Wasley
  • Patent number: 5733931
    Abstract: The present invention provides a cyclohexanediurea derivative, inclusive of its salt, represented by the following formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and they each represent a straight-chain or branched alkyl group having at least 3 carbons, a cycloalkyl group, a cycloalkyl group having a bridge head, a furyl group, a furyl lower alkyl group or an aralkyl group, A.sub.1 and A.sub.2 are the same or different and they each represent a phenyl, pyridyl, quinolyl, isoquinolyl or indolyl group which may have substituents; a process for production thereof; an intermediate thereof; pharmaceutical use, a method for treatment and use thereof.
    Type: Grant
    Filed: March 8, 1996
    Date of Patent: March 31, 1998
    Assignee: Nissin Food Products Co., Ltd.
    Inventors: Toshihiro Yamada, Yoichi Nobuhara, Ichinari Takagi, Shiho Furumoto, Kazuhiro Kobayashi, Kiyohito Ikemoto
  • Patent number: 5656632
    Abstract: Disclosed are compounds of the formula ##STR1## or the pharmaceutically acceptable salts thereof wherein the 6-membered A ring may be optionally substituted with up to four groups independently selected from halogen, hydroxy, lower alkyl, or lower alkoxy;Ar represents optionally substituted aryl or heteroarylZ represents carbon or nitrogen provided thatwhere Z is carbon, R.sub.11 represents hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy, or phenyl optionally substituted with one or two groups selected from hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy; andwhere Z is nitrogen, R.sub.11 represents an electron pair;R.sub.5 is hydrogen or lower alkyl;L and m represent integers;n is 0, or an integer;R.sub.12 and R.sub.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: August 12, 1997
    Assignee: Neurogen Corporation
    Inventors: Xiao-shu He, Brian de Costa, Jan W. F. Wasley
  • Patent number: 5607693
    Abstract: The invention relates to a cosmetic or pharmaceutical composition which comprises oxyacanthine, one of its derivatives, one of their cosmetically or pharmaceutically acceptable acid addition salts or an extract of a plant in which it is present, such as Berberis vulgaris or barberry. One particular association is that of oxyacanthine with a saponin. This composition can be intended in particular for stimulating hair growth, retarding hair loss or combating pruritus.
    Type: Grant
    Filed: June 1, 1995
    Date of Patent: March 4, 1997
    Assignee: LVMH Recherche
    Inventors: Frederic Bonte, Alain Meybeck
  • Patent number: 5604224
    Abstract: Substitutued heterocyclylisoquinolinium salts, pharmaceutical compositions containing them and methods for the treatment or prevention of neurodegenerative disorders or neurotoxic injuries utilizing them.
    Type: Grant
    Filed: May 30, 1995
    Date of Patent: February 18, 1997
    Assignee: Sterling Winthrop Inc.
    Inventors: John A. Dority, Jr., William G. Earley, Virendra Kumar, John P. Mallamo, Matthew S. Miller, Chakrapani Subramanyam
  • Patent number: 5602168
    Abstract: Disclosed are compounds of the formula ##STR1## or the pharmaceutically acceptable salts thereof wherein the 6-membered A ring may be optionally substituted with up to four groups independently selected from halogen, hydroxy, lower alkyl, or lower alkoxy;Ar represents optionally substituted aryl or heteroarylZ represents carbon or nitrogen provided thatwhere Z is carbon, R.sub.11 represents hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy, or phenyl optionally substituted with one or two groups selected from hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy; andwhere Z is nitrogen, R.sub.11 represents an electron pair;R.sub.5 is hydrogen or lower alkyl;L and m represent integers;n is 0, or an integer;R.sub.12 and R.sub.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: February 11, 1997
    Assignee: Neurogen Corporation
    Inventors: Xiao-shu He, Brian de Costa, Jan W. F. Wasley
  • Patent number: 5569655
    Abstract: Substitutued heterocyclylisoquinolinium salts, pharmaceutical compositions containing them and methods for the treatment or prevention of neurodegenerative disorders or neurotoxic injuries utilizing them.
    Type: Grant
    Filed: July 29, 1994
    Date of Patent: October 29, 1996
    Assignee: Sterling Winthrop Inc.
    Inventors: John A. Dority, Jr., William G. Earley, Virendra Kumar, John P. Mallamo, Matthew S. Miller, Chakrapani Subramanyam
  • Patent number: 5534523
    Abstract: An anti-AIDS virus composition comprising a therapeutically effective amount of cepharanthine or a pharmaceutically acceptable salt thereof and a method for treating AIDS which comprises administering a therapeutically effective amount of cepharanthine or a pharmaceutically acceptable salt thereof are disclosed.
    Type: Grant
    Filed: December 2, 1994
    Date of Patent: July 9, 1996
    Assignee: Kaken Shoyaku Co., Ltd.
    Inventors: Minoru Ono, Yuka Tamura, Michinori Akasu
  • Patent number: 5527811
    Abstract: Compounds represented by the formula: ##STR1## wherein the ring A and the ring B each stand for an optionally substituted benzene ring; Ar stands for an optionally substituted aryl group or an optionally substituted heterocyclic group; Q stands for an oxygen atom or a sulfur atom; R stands for a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group or an optionally substituted amino group; X stands for --O-- or --NR.sup.1 -- wherein R.sup.1 stands for a hydrogen atom or an optionally substituted hydrocarbon group; Y stands for --O--, --NR.sup.2 -- wherein R.sup.2 stands for a hydrogen atom or an optionally substituted hydrocarbon group, or a bond; m denotes 1, 2 or 3, and n denotes 0, 1 or 2, and salts thereof which have excellent calcium- or substance P receptor-antagonistic activity, being useful for treating a cerebralvascular disorder in mammals such as cerebralischemia, cerebral edema and neuronal damage, their production and use.
    Type: Grant
    Filed: July 13, 1994
    Date of Patent: June 18, 1996
    Assignee: Takeda Chemical Industries, Ltd.
    Inventors: Hideaki Natsugari, Tetsuji Imamoto, Yuzo Ichimori
  • Patent number: 5519033
    Abstract: The present invention relates to a method of treating urinary incontinence in mammals, including humans, using certain quinuclidine derivatives, piperidine derivatives, azanorbornane derivatives of azabiaglo and related compounds.
    Type: Grant
    Filed: May 31, 1994
    Date of Patent: May 21, 1996
    Assignee: Pfizer Inc.
    Inventors: Terry J. Rosen, Manoj C. Desai, John A. Lowe, III
  • Patent number: 5506243
    Abstract: Since sulfonamide derivatives of the present invention show strong inhibitory activity against cysteine protease such as calpain papain, cathepsin B, cathepsin H, cathepsin L, they can be used as remedies for muscular dystrophy, cataract, myocardial infarction, stroke, Alzheimer's disease, amyotrophia, osteoporosis, hypercalcemia or the like.
    Type: Grant
    Filed: April 28, 1994
    Date of Patent: April 9, 1996
    Assignee: Mitsubishi Kasei Corporation
    Inventors: Ryoichi Ando, Toshiro Sakaki, Chizuko Takahashi, Yoshiyuki Fujimura
  • Patent number: 5462963
    Abstract: The present invention involves photoprotective compositions which are useful for topical application to prevent damage to skin caused by acute or chronic exposure to ultraviolet light comprising chelating agents having the structure: ##STR1## wherein each --R.sup.1 is independently selected from the group consisting of alkyl, aryl, heteroaryl and heterocycle, or the --R.sup.1 's are covalently bonded together to form a cyclic alkyl or heterocyclic ring; --R.sup.2 and --R.sup.3 are --OR.sup.4, in which case there is no bond or a polar bond between --R.sup.2 and the nitrogen covalently bonded to --R.sup.3, each --R.sup.4 being independently selected from the group consisting of hydrogen, alkyl and aryl, except that both --R.sup.4 's are not methyl when both --R.sup.1 's are furyl; or --R.sup.2 is --O-- and is covalently bonded to the nitrogen which is covalently bonded to --R.sup.3, and --R.sup.3 is --O-- (there being a + charge on the nitrogen to which it is bonded) or nil;wherein the .alpha.
    Type: Grant
    Filed: August 2, 1991
    Date of Patent: October 31, 1995
    Assignee: The Procter & Gamble Company
    Inventors: Rodney D. Bush, Donald L. Bissett
  • Patent number: 5455251
    Abstract: The present invention provides new antiviral compounds, i.e., michellamines and derivatives and pharmacologically acceptable salts thereof, methods for isolating such antiviral compounds from a plant species of the genus Ancistrocladus, antiviral compositions containing such antiviral compounds, and methods of using such antiviral compounds for treating patients with viral infections. The antiviral compounds of the present invention inhibit the reproduction and cytopathicity of human acquired immunodeficiency viruses.
    Type: Grant
    Filed: April 19, 1993
    Date of Patent: October 3, 1995
    Assignee: The United States of America as represented by the Secretary of the Department of Health and Human Services
    Inventors: Michael R. Boyd, John H. Cardellina, II, Kirk P. Manfredi, John W. Blunt, Lewis K. Pannell, James B. McMahon, Robert J. Gulakowski, Gordon M. Cragg, Gerhard Bringmann, Duncan Thomas, Johnson Jato
  • Patent number: 5430041
    Abstract: Compounds of the formula: ##STR1## wherein R.sup.1 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aralkanoyl, heterocyclylcarbonyl or a group of the formula: ##STR2## R.sup.2 is alkyl, cycloalkylalkyl or aralkyl; R.sup.3 is hydrogen and R.sup.4 is hydroxy or R.sup.3 and R.sup.4 together are oxo; R.sup.5 is alkoxycarbonyl or alkylcarbamoyl; R.sup.6 and R.sup.7 together are trimethylene or tetramethylene optionally substituted by alkyl or on adjacent carbon atoms by tetramethylene; R.sup.8 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aroyl, aralkanoyl or heterocyclylcarbonyl; and R.sup.9 is alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, cyanoalkyl, carbamoyl-alkyl, alkylthioalkyl, alkoxyalkyl or alkoxycarbonylalkyl: and pharmaceutically acceptable acid addition salts of those compounds of formula I which are basic, inhibit aspartyl proteases of viral origin and can be used in the form of medicaments for the prophylaxis or treatment of viral infections.
    Type: Grant
    Filed: April 21, 1992
    Date of Patent: July 4, 1995
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Joseph A. Martin, Gareth J. Thomas
  • Patent number: 5416094
    Abstract: Described are guanidinocarbonyl isoquinolines of the formula I, ##STR1## wherein R(1) is hydrogen, (amino) (cyclo) (aryl)alk(en)yl (heteroaryl); R(2) is hydrogen, halogen, alkyl, or aryl; G is a radical of the formula VII: ##STR2## X(2), X(3) and X(4) are hydrogen, halogen, nitro, amino, alkyl, sulfonamide, (mono) (di) (lower alkyl) (amino), benzyloxy, hydroxy; X(1) hydrogen, oxygen, sulfur and NR(7)R(8), and their pharmaceutically acceptable salts; described is also a process for their preparation, their use as medicaments, and medicaments containing them for treating congestive heart failure, and arrhythmic conditions as well as cardioprotective agents in mammals.
    Type: Grant
    Filed: September 24, 1993
    Date of Patent: May 16, 1995
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Bansi Lal, Ramesh Gidwani, Ramanujam Rajagopalan, Radha Panicker, Chinnakulandai Sankar, Hans-Jochen Lang, Heinrich Englert, Wolfgang Scholz
  • Patent number: 5321032
    Abstract: A tachykinin-antagonistic compound of the following general formula:R.sup.1 --A.sup.1 --D--Trp(R.sup.2)--A.sup.2 --R.sup.3[whereinR.sup.1 is hydrogen or amino-protective groupR.sup.2 is amino-protective groupR.sup.3 is ar(lower)alkoxy or N-(lower)alkyl or N-ar(lower)alkylaminoA.sup.1 is single bond or one amino acid residueA.sup.2 is one amino acid residue other than Phe.]or the salt thereof.
    Type: Grant
    Filed: August 12, 1992
    Date of Patent: June 14, 1994
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Masaaki Matsuo, Daijiro Hagiwara, Hiroshi Miyake
  • Patent number: 5283245
    Abstract: The invention concerns a thiazole of the formula I, ##STR1## wherein Q.sup.1 is an optionally substituted 6-membered monocyclic or 10-membered bicyclic heterocyclic moiety containing one or two nitrogen atoms;X is oxy, thio, sulphinyl, sulphonyl or imino;Ar is phenylene which may optionally bear one or two substituents, or Ar is an optionally substituted 6-membered heterocyclene moiety contining up to three nitrogen atoms;R.sup.1 is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl or substituted (1-4C)alkyl;R.sup.2 is hydrogen, (1-6C)alkyl, (3-6C)alkenyl, (3-6C)alkynyl or substituted (1-4C)alkyl or R.sup.2 is optionally substituted benzoyl; andQ.sup.2 is optionally substituted thiazolyl;or a pharmaceutically-acceptable salt thereof.The invention also concerns processes for the manufacture of a thiazole of the formula I and pharmaceutical compositions containing said thiazole.
    Type: Grant
    Filed: November 18, 1991
    Date of Patent: February 1, 1994
    Assignees: Imperial Chemical Industries PLC, ICI Pharma
    Inventors: Graham C. Crawley, Martin P. Edwards
  • Patent number: 5244895
    Abstract: An anti-ulcer agent contains a compound expressed by the following general formula 1: ##STR1## where, R.sub.1 is hydrogen atom or an alkyl group having 1 or 2 carbon atoms with or without substitution, R.sub.2 and R.sub.3 are resp. hydrogen atom or form oxo group together, R.sub.4 is hydrogen atom or methyl group or isoquinoline sulfonyl group, n is 2 or 3, A is N--R.sub.5 or CH--R.sub.5, R.sub.5 is phenyl group with or without substitution or benzyloxycarbonyl group with or without substitution, or a physiologically allowable acid added salt thereof as the active component.
    Type: Grant
    Filed: May 15, 1992
    Date of Patent: September 14, 1993
    Assignee: Hiroyoshi Hidaka
    Inventors: Hiroyoshi Hidaka, Tomohiko Ishikawa
  • Patent number: 5240939
    Abstract: Muscle relaxant nitrogen bridge tetrahydroisoquinolines are disclosed. The novel compounds are represented by the formula ##STR1## wherein A is ##STR2## M represents --(CH.sub.2).sub.n --Z--(CH.sub.2).sub.n or ##STR3## R is a C.sub.1-3 alkoxy group, or adjacent Rs are a methylenedioxy group, R.sub.1 is lower alkyl; n is 1-6;m is 2 or 3; p is 1-3; Z is --N.sup.+ (R.sub.2 R.sub.3)--, --N(R.sub.4)--, ##STR4## and --N[(CH.sub.2).sub.n --A--R.sub.5 ]--; R.sub.2 and R.sub.3 are independently lower alkyl groups wherein a carbon atom within the chain may be replaced by a heteroatom, lower cycloalkyl, lower cycloalkyl lower alkyl, aryl, aryl lower alkyl, a 4- to 6-member heteroring or may be combined with the nitrogen to form a heteroring; R.sub.4 is a straight- or branched- chain C.sub.1-10 alkyl wherein a carbon atom within the chain may be replaced by a heteroatom, lower cycloalkyl, lower cycloalkyl lower alkyl, aryl, or a heteroring, which groups may be substituted or unsubstituted; or ##STR5## R.sub.
    Type: Grant
    Filed: November 16, 1992
    Date of Patent: August 31, 1993
    Assignee: Anaquest, Inc.
    Inventor: Donald M. Demko
  • Patent number: 5212179
    Abstract: The invention concerns the preparation of compounds of formula ##STR1## and acid addition and quaternary ammonium salts thereof, wherein the dotted line represents an optional bond, Ar represents a ring system of formula ##STR2## in which Q is O, S, --CR.sup.7 .dbd.CR.sup.8 --, --N.dbd.CR.sup.8 -- and --N.dbd.N--; R.sup.4, R.sup.5 and R.sup.6 ; and R.sup.7 and R.sup.8 when present, each represent hydrogen or a substituent selected from lower alkyl, lower alkenyl, lower alkoxy, NO.sub.2, NH.sub.2, haloloweralkyl, hydroxyloweralkyl, aminoloweralkyl, substituted amino, halogen, loweralkoxycarbonyl, cyano, CONH.sub.2 and hydroxy; and additionally either R.sup.4 and R.sup.5 when adjacent or R.sup.6 and R.sup.
    Type: Grant
    Filed: October 25, 1990
    Date of Patent: May 18, 1993
    Assignee: John Wyeth and Brother Limited
    Inventors: John L. Archibald, Terence J. Ward
  • Patent number: 5190961
    Abstract: Thiourea derivatives represented by the formula (I) ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and each represents a lower alkyl group, or R.sub.1 or R.sub.2 taken together represent a group having the formula --(CH.sub.2).sub.m --in which m is 4 or 5, R.sub.3 represents a lower alkyl group or a cycloalkyl group or a group having the formula--(CH.sub.2).sub.l --R.sub.4 in which R.sub.4 is a phenyl, naphthyl, pyridyl, furyl or thienyl group optionally having 1-3 substituents selected from the group consisting of lower alkyl, lower alkoxy, phenoxy, lower alkylthio, hydroxy, halogen, nitro, cyano and trifluoromethyl, and l represents an integer of 0 to 2 and n represents an integer of 1 to 5 or a physiologically acceptable salt thereof.The compounds of the invention are useful as a therapeutic agent for peptic ulcers which is also effective on prevention of the recurrence after discontinuation of the administration due to the antimicrobial activity against Helicobacter pyroli.
    Type: Grant
    Filed: August 2, 1991
    Date of Patent: March 2, 1993
    Assignee: Terumo Kabushiki Kaisha
    Inventors: Hirokazu Hasegawa, Isamu Endo, Shingo Koyama, Masashi Isozaki, Yukari Yoshiyama, Shigenori Nozawa, Norio Arakawa
  • Patent number: 5158959
    Abstract: What are disclosed are aminoacid compounds of the formula ##STR1## wherein n is 0 or 1, and salts thereof, said compounds and salts having hypotensive properties; methods for making the compounds; pharmaceutical compositions containing the compounds or salts; and use of the compounds and salts for treating hypertension.
    Type: Grant
    Filed: December 27, 1983
    Date of Patent: October 27, 1992
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Rolf Geiger, Volker Teetz, Hansjorg Urbach, Bernward Scholkens, Rainer Henning
  • Patent number: 5068337
    Abstract: The invention concerns compounds of formula ##STR1## or salts thereof; wherein Ar is an optionally substituted aryl radical;R represents hydrogen or an optionally substituted alkyl or aralkyl group;R.sup.1 and R.sup.2 are the same or different and are selected from hydrogen and saturated or unsaturated, cyclic or acyclic aliphatic hydrocarbon residues optionally substituted by one or more groups selected from halogen, OH, carboxy, CN, alkoxy, alkylthio, aryloxy, alkoxycarbonyl, amino, substituted amino, and optionally substituted aryl;A represents a group of formula --XR.sup.3 whereinX is (i) a group of formula --(CHR.sup.6).sub.p --Y--(CHR.sup.7).sub.q --or (ii) a group of formula --(CHR.sup.6).sub.r --O--(CHR.sup.7).sub.qin which formulae: Y represents --S--, NR.sup.8 or a direct bond, p and q each represent 0, 1 or 2 providing that p and q do not both represent 0, 1 or 2 and the other is zero; R.sup.6, R.sup.7 and R.sup.8 independently represent hydrogen or lower alkyl, and R.sup.
    Type: Grant
    Filed: November 13, 1986
    Date of Patent: November 26, 1991
    Assignee: John Wyeth & Brother Limited
    Inventors: John L. Archibald, Terence J. Ward, Albert Opalko
  • Patent number: 5032591
    Abstract: A pharmaceutical product comprising a potassium channel activator antihypertensive agent and a .beta.-blocker antihypertensive agent as a combined preparation for simultaneous, separate or sequential use in therapy of hypertension.
    Type: Grant
    Filed: January 4, 1989
    Date of Patent: July 16, 1991
    Assignee: Beecham Group p.l.c.
    Inventors: John M. Evans, Robin E. Buckingham
  • Patent number: 5032590
    Abstract: Substituted hydroxylamines of the formula ##STR1## in which R.sup.1 stands for an aromatic or heterocyclic radical,are especially useful in the treatment of hyperlipoproteinaemia, lipoproteinaemia and atherosclerosis.
    Type: Grant
    Filed: March 8, 1990
    Date of Patent: July 16, 1991
    Assignee: Bayer Aktiengesellschaft
    Inventors: Walter Hubsch, Rolf Angerbauer, Peter Fey, Hilmar Bischoff, Dieter Petzinna, Delf Schmidt
  • Patent number: 4975438
    Abstract: Compounds of the formula ##STR1## Y is O or S, *A is paraphenylene or *--(CH.sub.2).sub.n --(X).sub.m --(CH.sub.2).sub.r --, X is O, S or --CH.dbd.CH--, n or r, independently, are integers from 0 to 3, s is an integer from 0 to 1, m is an integer from 0 to 1, provided that when m is 1, n+s must be at least 2, R.sub.1 and R.sub.2, independently, are hydrogen, lower alkyl, cycloalkyl, lower alkenyl, Het, Aryl, R.sub.3, R.sub.4 and R.sub.8, independently, are hydrogen, lower alkyl, aryl, R.sub.5 and R.sub.6, independently, are hydrogen or lower alkyl, R.sub.7 is hydrogen, lower alkyl, cycloalkyl, Het-lower alkyl or aryl, Het is a monocyclic 5- or 6-membered hetero aromatic or a bicyclic heteroaromatic radical containing one or two hetero atoms selected from nitrogen, oxygen and sulfur, which radical may be substituted by lower alkyl, halogen or aryl, and the asterisk denotes the point of attachment,and when R.sub.6 and R.sub.7 are different, their enantiomers and racemic mixtures thereof, when R.sub.1 and R.sub.
    Type: Grant
    Filed: September 6, 1988
    Date of Patent: December 4, 1990
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Robert W. Guthrie, Richard W. Kierstead, Jefferson W. Tilley
  • Patent number: 4968681
    Abstract: Substituted hydroxylamines of the formula ##STR1## in which R.sup.1 stands for an aromatic or heterocyclic radical, are especially useful in the treatment of hyperlipoproteinaemia, lipoproteinaemia and atherosclerosis.
    Type: Grant
    Filed: November 15, 1988
    Date of Patent: November 6, 1990
    Assignee: Bayer Aktiengesellschaft
    Inventors: Walter Hubsch, Rolf Angerbauer, Peter Fey, Hilmar Bischoff, Dieter Petzinna, Delf Schmidt
  • Patent number: 4954518
    Abstract: This invention relates to a 4H-1-benzopyran-4-one derivative represented by the formula: ##STR1## or a salt thereof, a process for producing the same and a pharmaceutical composition comprising the same as active ingredient.
    Type: Grant
    Filed: October 7, 1988
    Date of Patent: September 4, 1990
    Assignee: Toyama Chemical Company, Ltd.
    Inventors: Shuntaro Takano, Chosaku Yoshida, Takihiro Inaba, Keiichi Tanaka, Ryuko Takeno, Hideyoshi Nagaki, Tomoya Shimotori, Shinji Makino
  • Patent number: 4937255
    Abstract: For inhibiting 3-hydroxy-3-methylglutaryl coenzyme A and cholesterol biosynthesis, the novel disubstituted pyrroles of the formula ##STR1## in which R.sup.1 is aryl or heteroaryl,R.sup.2 is cycloalkyl or optionally substituted alkyl,R.sup.3 is hydrogen or cycloalkyl, or optionally substituted alkyl, aryl or heteroaryl,X is --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--,A is ##STR2## R.sup.6 is hydrogen or alkyl, and R.sup.7 is hydrogen, a cation or alkyl, aryl or aralkyl.
    Type: Grant
    Filed: March 16, 1989
    Date of Patent: June 26, 1990
    Assignee: Bayer Aktiengesellschaft
    Inventors: Walter Hubsch, Rolf Angerbauer, Peter Fey, Hilmar Bischoff, Dieter Petzinna, Delf Schmidt, Gunter Thomas
  • Patent number: 4833152
    Abstract: Novel inhibitors of angiotensin coverting enzyme having the general formula R - A - S - Z are disclosed as potent inhibitors of angiotensin converting enzyme and are useful anti-hypertensive agents.
    Type: Grant
    Filed: November 20, 1987
    Date of Patent: May 23, 1989
    Assignee: University of Miami
    Inventors: James W. Ryan, Alfred Chung
  • Patent number: 4808627
    Abstract: A method is provided for preventing or treating toxemia during pregnancy by administering a thromboxane A.sub.2 receptor antagonist before or during toxemia.
    Type: Grant
    Filed: December 16, 1987
    Date of Patent: February 28, 1989
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Martin L. Ogletree
  • Patent number: 4761418
    Abstract: Neuromuscular blocking agents of formula (1) which are useful as skeletal muscle relaxants during surgery are disclosed. ##STR1## and X is an anion, preferably pharmaceutically acceptable.
    Type: Grant
    Filed: July 17, 1985
    Date of Patent: August 2, 1988
    Assignees: Burroughs Wellcome Co., General Hospital Corporation
    Inventors: Roy A. Swaringen, Jr., Hassan A. El-Sayad, David A. Yeowell, John J. Savarese
  • Patent number: 4749698
    Abstract: Compounds having the general structure ##STR1## and their pharmaceutically acceptable salts, wherein the substituents are defined herein, which exhibit antihypertensive activity.
    Type: Grant
    Filed: July 8, 1985
    Date of Patent: June 7, 1988
    Assignee: Rorer Pharmaceutical Corporation
    Inventors: Edward S. Neiss, John T. Suh, John R. Regan, Jerry W. Skiles, Jeffrey N. Barton, James J. Mencel, Paul Menard
  • Patent number: 4745124
    Abstract: Novel thiolester compounds are disclosed which are orally effective angiotensin converting enzyme inhibitors useful in the treatment of mammalian hypertension. They have the formula,R.sub.1 -A.sub.1 -S-Z,wherein Z denotes -B-A.sub.2, R.sub.1 is H or an acyl group, A.sub.1 is a carboxylic acid containing at least one amino or imino -N-, A.sub.2 is a carboxylic acid containing at least one amino or imino -N- or a lower alkyl ester or amide thereof, B is a 2-4 carbon backbone chain in mercapto linkage to S which includes a carbonyl or sulfonyl group joined in carboxamido or sulfonamido linkage, respectively, to A.sub.2.Preferably A.sub.2 includes a 4-6 membered C-N ring or a 5 membered ring of one N, one S and 3 C atoms.
    Type: Grant
    Filed: July 20, 1983
    Date of Patent: May 17, 1988
    Assignee: University of Miami
    Inventors: James W. Ryan, Alfred Chung
  • Patent number: 4734420
    Abstract: Novel inhibitors of angiotensin converting enzyme having the general formula R - A - S - Z are disclosed as potent inhibitors of angiotensin converting enzyme and are useful anti-hypertensive agents.
    Type: Grant
    Filed: May 2, 1980
    Date of Patent: March 29, 1988
    Assignee: University of Miami
    Inventors: James W. Ryan, Alfred Chung
  • Patent number: 4701460
    Abstract: Long duration muscle relaxant compound of formula (I) ##STR1## and its use in producing muscle relaxation in mammals including man.
    Type: Grant
    Filed: January 25, 1985
    Date of Patent: October 20, 1987
    Assignee: Burroughs Wellcome Co.
    Inventors: Hassan A. El-Sayad, Roy A. Swaringen, Jr., David A. Yeowell
  • Patent number: 4698352
    Abstract: This invention relates to a novel 4-oxo-1,4-dihydronicotinic acid derivative ##STR1## or a salt thereof, wherein R.sup.1 is hydrogen or carboxyl-protecting group;R.sup.2 is substituted phenyl and naphthyl, or a substituted or unsubstituted heterocyclic group; andR.sup.3 is haloalkyl, aminoalkyl, or substituted or unsubstituted alkenyl, phenylalkenyl, naphthylalkenyl, phenylalkyl, naphthylalkyl, phenylalkynyl, naphthylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, phenyl, naphthyl, cycloalkyl, cycloalkenyl, carboxylic acyl, iminoalkyl, heterocyclic or bridged hydrocarbon, which has a broad antibacterial spectrum and a low toxicity, and are useful for treatment of diseases of human beings and animals, to a process for producing the same and to an antibacterial agent containing the same.
    Type: Grant
    Filed: October 27, 1983
    Date of Patent: October 6, 1987
    Assignee: Toyama Chemical Co., Ltd.
    Inventors: Hirokazu Narita, Yoshinori Konishi, Jun Nitta, Shunjiro Misumi, Hideyoshi Nagaki, Isao Kitayama, Yoriko Nagai, Yasuo Watanabe, Nobuyuki Matsubara, Shinzaburo Minami, Isamu Saikawa
  • Patent number: 4698356
    Abstract: Novel compounds are disclosed as potent inhibitors of angiotensin converting enzyme and as orally effective antihypertensive agents.
    Type: Grant
    Filed: August 14, 1979
    Date of Patent: October 6, 1987
    Assignee: University of Miami
    Inventors: James W. Ryan, Alfred Chung
  • Patent number: 4698355
    Abstract: Novel compounds are disclosed as potent inhibitors of angiotensin converting enzyme and as orally effective antihypertensive agents.
    Type: Grant
    Filed: August 14, 1979
    Date of Patent: October 6, 1987
    Assignee: University of Miami
    Inventors: James W. Ryan, Alfred Chung
  • Patent number: 4695577
    Abstract: Novel compounds are disclosed as potent inhibitors of angiotensin converting enzyme and as orally effective antihypertensive agents.
    Type: Grant
    Filed: August 14, 1979
    Date of Patent: September 22, 1987
    Assignee: University of Miami
    Inventors: James W. Ryan, Alfred Chung
  • Patent number: 4692459
    Abstract: Inhibitors of angiotensin converting enzyme which have the formula: ##STR1## wherein R is hydrogen, formyl, acetyl propanoyl, butanoyl, phenylacetyl, phenylpropanoyl, benzoyl, cyclopentanecarbonyl, tert-butyloxycarbonyl, cyclopentanecarbonyl-L-lysyl, pyro-L-glutamyl-L-lysyl, L-lysyl, L-arginyl or pyro-L-glutamyl;A is L-phenylalanyl, D-phenylalanyl, D,L-alanyl, D-alanyl, D,L-tryptophyl, D-tryptophyl, D,L-tyrosyl, D-tyrosyl, D,L-isoleucyl, D-isoleucyl, D,L-leucyl, D-leucyl, D,L-histidyl, D-histidyl, D,L-valyl, or D-valyl, the .alpha.-amino group thereof being in amide linkage with R;R.sub.1 is hydrogen or methyl;R.sub.2 is L-proline, L-3,4-dehydroproline, D,L-3,4-dehydroproline, L-3-hydroxyproline, L-4-hydroxyproline, L-thiazolidine-4-carboxylic acid, or L-5-oxo-proline, the imino group thereof being in imide linkage with the adjacent ##STR2## and, n is 0 or 1, such that when n is 0, R.sub.1 is methyl are disclosed as useful anti-hypertensive agents.
    Type: Grant
    Filed: March 3, 1980
    Date of Patent: September 15, 1987
    Assignee: University of Miami
    Inventors: James W. Ryan, Alfred Chung
  • Patent number: 4692458
    Abstract: Novel inhibitors of angiotensin converting enzyme having the general formula R--A--S--Z are disclosed as potent inhibitors of angiotensin converting enzyme and are useful anti-hypertensive agents.
    Type: Grant
    Filed: March 5, 1980
    Date of Patent: September 8, 1987
    Assignee: University of Miami
    Inventors: James W. Ryan, Alfred Chung
  • Patent number: 4690940
    Abstract: Novel Compounds are disclosed as potent inhibitors of angiotensin converting enzyme and as orally effective antihypertensive agents.
    Type: Grant
    Filed: August 14, 1979
    Date of Patent: September 1, 1987
    Assignee: University of Miami
    Inventors: James W. Ryan, Alfred Chung
  • Patent number: 4690939
    Abstract: Novel compounds are disclosed as potent inhibitors of angiotensin converting enzyme and as orally effective anti-hypertensive agents.
    Type: Grant
    Filed: August 14, 1979
    Date of Patent: September 1, 1987
    Assignee: University of Miami
    Inventors: James W. Ryan, Alfred Chung