Additional -coo- Group Bonded Directly To The Six-membered Hetero Ring Patents (Class 546/321)
  • Patent number: 4806533
    Abstract: Compounds are described of the formula ##STR1## wherein R.sub.1 and R.sub.4 independently represent a C.sub.1-4 alkyl group;R.sub.2 and R.sub.3 independently represent a C.sub.1-6 straight or branched alkyl chain or alkoxy group;R.sub.5 represents a straight or branched chain C.sub.1-13 alkyl group or a C.sub.5-8 cycloalkyl group which may be substituted by a C.sub.1-3 alkyl substituent;R.sub.6 represents a halogen atom or a straight or branched C.sub.1-3 alkyl group.R.sub.7 represents a C.sub.1-4 alkyl group [optionally substituted by hydroxy, C.sub.1-3 alkoxy or trifluoromethyl or by a group NR.sub.8 R.sub.9 where NR.sub.8 R.sub.9 forms a saturated 5 to 7 membered ring optionally containing an additional heleroatom which is oxygen]; or R.sub.7 represents a phenylC.sub.1-2 alkyl group in which the phenyl portion is optionally substituted by 1 to 3 C.sub.1-3 alkyl or C.sub.1-3 alkoxy groups or halogen atoms.
    Type: Grant
    Filed: February 19, 1987
    Date of Patent: February 21, 1989
    Assignee: Glaxo, s.p.a.
    Inventors: Claudio Semeraro, Dino Micheli, Daniele Pieraccioli, Giovanni Gaviraghi, Alan D. Borthwick
  • Patent number: 4806557
    Abstract: A compound of the formula: ##STR1## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is amino, hydroxy, alkoxy, phenoxy or benzyloxy, useful in the treatment of hypertension, angina, renal impairment or acute renal failure.
    Type: Grant
    Filed: April 28, 1988
    Date of Patent: February 21, 1989
    Assignee: Pfizer Inc.
    Inventors: Simon F. Campbell, Michael J. Humphrey, Alan Stobie
  • Patent number: 4801599
    Abstract: Compounds are described of the formula ##STR1## wherein R.sub.1 and R.sub.4 independently represent a C.sub.1-4 alkyl group;R.sub.2 and R.sub.3 independently represent a C.sub.1-6 straight or branched alkyl chain which may be interrupted by an oxygen atom;R.sub.5 represents a straight or branched chain C.sub.1-13 alkyl group or a C.sub.5-8 cycloalkyl group which may be substituted by a C.sub.1-3 alkyl substitutent;The compounds represented by formula (I) reduce intracellular calcium ion cencentration by limiting transmembranal calcium ion influx and thus may be useful for the treatment of cardiovascular disorders such as hypertension.
    Type: Grant
    Filed: August 20, 1985
    Date of Patent: January 31, 1989
    Assignee: GLAXO S.P.A.
    Inventors: Claudio Semeraro, Dino Micheli, Daniele Pieraccioli, Giovanni Gaviraghi, Allan D. Borthwick
  • Patent number: 4798840
    Abstract: Hypotensive long-acting 1,4-dihydropyridines of the formula ##STR1## in which R.sup.1 is phenyl or heterocyclic,R.sup.2, R.sup.3, R.sup.4 and R.sup.5 have the usual definitions in such compounds,R.sup.6 represents hydrogen or a lower alkyl radical or the trifluoromethyl group,R.sup.7 and R.sup.8 each denote a hydrogen atom or a fluorine atom,n.gtoreq.1 andm.gtoreq.0, and the sum of n and m must be a least 4, andX represents a single bond, an oxygen atom or the group --N(alkyl)--O.sub.2 S--,or pharmacologically acceptable acid addition salts thereof.
    Type: Grant
    Filed: December 4, 1986
    Date of Patent: January 17, 1989
    Assignee: Bayer Aktiengesellschaft
    Inventors: Egbert Wehinger, Horst Meyer, Andreas Knorr, Stanislav Kazda
  • Patent number: 4795814
    Abstract: Process for preparing dihydropyridine derivatives and salts and esters thereof represented by the general formula ##STR1## from a phenyl derivative and an enamine derivative in which the phenyl derivative is prepared by reacting a compound of the formula ##STR2## with a compound of the formula ##STR3## in the presence of an aromatic amine selected from o-, m-, p- anisidine; m-, p-toluidine; p-chloroaniline; aniline and o-phenetidine.
    Type: Grant
    Filed: December 18, 1986
    Date of Patent: January 3, 1989
    Assignee: Otsuka Pharmaceutical Co., Ltd.
    Inventors: Shinji Nishitani, Junichi Minamikawa, Masanobu Kano, Junichiro Otsubo, Yoshiaki Manabe
  • Patent number: 4794187
    Abstract: A radioactively labelled dihydropyridine compound of the formula ##STR1## in which R.sup.1 represents a phenyl radical which is optionally substituted once or twice, identically or differently, by halogen, nitro, trifluoromethyl or difluoromethoxy, or R.sup.1 represents benzoxadiazolyl,R.sup.2 represents a straight-chain or branched alkyl which has up to 8 carbon atoms and which is optionally substituted by cyano, phenyl, halogen, N-benzyl-N-methylamino, N-phenylpiperazino or by alkoxy having up to 4 carbon atoms, andR.sup.3 and R.sup.4 are identical or different and each represents a cyano or represents a straight-chain or branched alkyl which has up to 6 carbon atoms, is optionally interrupted in the chain by one oxygen atom and is optionally substituted by hydroxyl or amino. The compounds are useful in investigating the pharmacokinetics and pharmacodynamics of dihydropyridines, especially for determining metabolism, modes of elimination and organ-specific action.
    Type: Grant
    Filed: January 5, 1987
    Date of Patent: December 27, 1988
    Assignee: Bayer Aktiengesellschaft
    Inventor: Hartmut Glossmann
  • Patent number: 4786641
    Abstract: Blood-sugar-lowering dihydropyridines of the formula ##STR1## in which R.sup.1 represents phenyl, naphthyl, thienyl, pyridyl, chromenyl or thiochromenyl, it being possible for the radicals mentioned each to carry up to 2 identical or different substituents from the series comprising halogen, alkyl, alkoxy and alkylthio with in each case up to 6 carbon atoms, fluoroalkyl and fluoroalkoxy with in each case up to 3 carbon atoms and 3 fluorine atoms, nitro and cyano,R.sup.2 represents straight-chain, branched or cyclic alkyl which has up to 8 carbon atoms, can be interrupted in the alkyl chain by an oxygen or a sulphur atom and can be substituted by halogen, phenyl, cyano, hydroxyl, amino, alkylamino or dialkylamino with in each case up to 3 carbon atoms per alkyl group or by N-benzylmethylamino,R.sup.
    Type: Grant
    Filed: August 20, 1987
    Date of Patent: November 22, 1988
    Assignee: Bayer Aktiengesellschaft
    Inventors: Siegfried Goldmann, Hans-Jurgen Ahr, Walter Puls, Hilmar Bischoff, Dieter Petzinna, Klaus Schlossmann, Joachim Bender
  • Patent number: 4784958
    Abstract: A simple method for preparing highly radioactive 1,4-dihydropyridine and 1,4-dihydroquinoline derivatives labelled with .sup.125 I enables a specific radioactivity of approx. 2200 to 8800 Ci/m Mole to be achieved. In this way high sensitivity in medicament screening with the aid of radioreceptor assays and in determining plasma levels of 1,4-dihydropyridines, 1,4-dihydroquinolines and other substances that inter-react with receptors for 1,4-dihydropyridines and 1,4-dihydroquinolines is achieved, with the result that a substantially shorter exposure time in the auto-radiographic identification of the receptors for these substances is required. For this purpose an amino derivative of a 1,4-dihydropyridine or 1,4-dihydroquinoline is reacted with an acylating reagent radiactively labelled with .sup.125 I (2200-4400 Ci/mMole), and the .sup.
    Type: Grant
    Filed: November 19, 1984
    Date of Patent: November 15, 1988
    Inventor: Hartmut Glossman
  • Patent number: 4782160
    Abstract: A 1,4-dihydropyridine derivative represented by general formula (I): ##STR1## wherein: R.sup.1 and R.sup.2 : which may be the same or different, each represents an alkyl group which may be intervened by an oxygen atom, a cycloalkyl-substituted lower alkyl group or a halogen-substituted lower alkyl group;R.sup.3 and R.sup.4 : which may be the same or different, each represents a lower alkyl group;R.sup.5 and R.sup.6 : which may be the same or different, each represents a hydrogen atom, a nitro group, a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfonyl group or a lower alkylsulfinyl group;R.sup.7 : hydrogen atom or a lower alkyl group;R.sup.8 : a lower alkyl group; a hydroxy-lower alkyl group, an aralkyl group, an aryl group, a lower acyl group, a lower alkylsulfonyl group or an aryloxy-lower alkyl group, an aryloxy-lower alkoxy group, provided that R.sup.7 and R.sup.
    Type: Grant
    Filed: December 8, 1987
    Date of Patent: November 1, 1988
    Assignee: Yamanouchi Pharmaceutical Co., Ltd.
    Inventors: Takashi Fujikura, Yuzo Matsumoto
  • Patent number: 4780538
    Abstract: A process for the preparation of 1,4-dihydropyridine compounds, especially N-substituted 1,4-dihydropyridine compounds, is disclosed. The compounds are useful as cardiovascular agents and also as starting materials for the preparation of certain cyclized compounds which have properties as calcium entry blockers.
    Type: Grant
    Filed: February 12, 1986
    Date of Patent: October 25, 1988
    Assignee: Merck & Co., Inc.
    Inventors: Steven M. Pitzenberger, Barry M. Trost
  • Patent number: 4775763
    Abstract: Metal values are extracted from aqueous solutions of metal salts containing halide or pseudo halide ions by pyridine derivatives containing the substituent --(COX).sub.A where X is the group --OR.sub.1 or --NR.sub.2 R.sub.3 and n is 1, 2 or 3. R.sub.1 is a hydrocarbyl group containing from 5 to 36 carbon atoms and R.sub.2 and R.sub.3 are hydrogen or a hydrocarbyl group wherein R.sub.2 and R.sub.3 together contain from 5 to 36 carbon atoms. The process is especially useful for the recovery of metals from leach solutions derived from sulphur-containing ores such as chalcopyrite.
    Type: Grant
    Filed: March 27, 1985
    Date of Patent: October 4, 1988
    Assignee: Imperial Chemical Industries
    Inventors: Raymond F. Dalton, Raymond Price, Peter M. Quan, David Stewart
  • Patent number: 4772612
    Abstract: Novel circulation active dihydropyridines of the formula ##STR1## in which X is CO, SO.sub.2 or CONH,R.sup.4 is H, OH, alkyl, halogen, acyloxy, alkoxyalkoxy, aralkyloxy, or together with R.sup.5 forms a heterocyclic ring, andthe other radicals are conventional in the dihydropyridine art,and pharmaceutically acceptable salts thereof.
    Type: Grant
    Filed: June 3, 1986
    Date of Patent: September 20, 1988
    Assignee: Bayer Aktiengesellschaft
    Inventors: Siegfried Goldmann, Jurgen Stoltefuss, Gerhard Franckowiak, Rainer Gross, Matthias Schramm, Gunter Thomas
  • Patent number: 4772695
    Abstract: A process for the preparation of vinyl carbamates of formula I ##STR1## is described which comprises heating an .alpha.-halogeno-carbamate of formula II ##STR2## in which X is a halogen atom at a temperature between 70.degree. and 250.degree. C. for a period of time between several minutes up to several hours. R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are the same or different. The process is applicable to a great variety of products in which R.sub.1, R.sub.2, R.sub.3, and R.sub.4 have different meanings. The process permits to prepare in a simple and economical fashion, vinyl carbamates, which have industrial value and novel vinyl carbamates.
    Type: Grant
    Filed: September 19, 1983
    Date of Patent: September 20, 1988
    Assignee: Societe Nationale des Poudres et Explosifs
    Inventors: Roy A. Olofson, Gary P. Wooden, Jonathan T. Martz
  • Patent number: 4772621
    Abstract: Novel antihypertensive and coronary dilating asymmetric diesters of 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylic acid (or the stereoisomers or pharmaceutically acceptable acid addition salts thereof) have the general formula (I): ##STR1## wherein Ph is phenyl, Ar is 2-nitrophenyl, 3-nitrophenyl, 2,3-dichlorophenyl or benzofurazan-4-yl, A is a straight or branched chain alkylene radical having from 2 to 6 carbon atoms, R is a straight or branched chain alkyl radical having from 1 to 6 carbon atoms, optionally mono-substituted by an alkoxy substituent having from 1 to 6 carbon atoms, R.sub.1 is hydrogen, hydroxy or an alkyl radical having from 1 to 4 carbon atoms, and R.sub.2 is hydrogen or methyl. The subject diesters are facilely prepared from the aldehydes ArCHO and esters of acetoacetic and 3-aminocrotonic acids.
    Type: Grant
    Filed: August 19, 1987
    Date of Patent: September 20, 1988
    Assignee: Recordati S.A., Chemical and Pharmaceutical Company
    Inventors: Dante Nardi, Amedeo Leonardi, Gabriele Graziani, Giorgio Bianchi
  • Patent number: 4771057
    Abstract: Pharmaceutical compounds of the general formula (1): ##STR1## have been prepared and non-toxic pharmaceutically acceptable salts thereof, wherein the ring system is a 1,2- or 1,4-dihydropyridyl radical; R.sub.1 is a hydrogen, lower alkyl, lower alkyl carbonyl or lower alkoxy carbonyl substituent; R.sub.2 is a lower alkly or phenyl substituent; R.sub.3 is a lower alkoxy carbonyl, (N,N-lower dialkylamino) lower alkoxy carbonyl, (N-lower alkyl-N-phenyl lower alkyl amino) lower alkoxy carbonyl, lower alkoxy lower alkoxy carbonyl, nitro, or cyano substituent; R.sub.
    Type: Grant
    Filed: February 3, 1986
    Date of Patent: September 13, 1988
    Assignee: University of Alberta
    Inventors: Edward E. Knaus, Michael W. Wolowyk, Lina Dagnino, Moy C. Li-Kwong-Ken, Donald A. Soboleski, Hla Wynn
  • Patent number: 4771059
    Abstract: The subject compounds, which are adapted for the site-specific/sustained delivery of centrally acting drug species to the brain, are compounds of the formula ##STR1## and the non-toxic pharmaceutically acceptable salts thereof, wherein D is the residue of a centrally acting primary, secondary or tertiary amine and ##STR2## is an unsubstituted or substituted dihydropyridyl, dihydroquinolyl or dihydroisoquinolyl radical. The corresponding ionic pyridinium, quinolinium and isoquinolinium salts ##STR3## X.sup.-, wherein X.sup.- is the anion of a non-toxic pharmaceutically acceptable acid, are also disclosed.
    Type: Grant
    Filed: August 29, 1985
    Date of Patent: September 13, 1988
    Assignee: University of Florida
    Inventor: Nicholas S. Bodor
  • Patent number: 4769465
    Abstract: A new, technologically easily feasible process for the preparation of 2-(N-benzyl-N-methylamino)ethyl methyl 2,6-dimethyl-4(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, comprising a partrial hydrolysis of dimethyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate in an inert organic solvent at a temperature between room temperature and the reflux temperature of the reaction mixture with an aqueous solution of alkali hydroxide and the reaction of the obtained 3-methoxycarbonyl-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-5-car boxylic acid either with N-(2-hydroxyethyl)-N-benzyl-methylamine in the presence or absence of an organic solvent in the presence of N,N'-dicyclohexylcarbodiimide at a temperature of between 25.degree. and 120.degree. C. or with N-(2-haloethyl)-N-benzyl-methylamine in the presence of an inert organic solvent and of a proton acceptor at a temperature of between 25.degree. and 140.degree. C.
    Type: Grant
    Filed: May 14, 1986
    Date of Patent: September 6, 1988
    Assignee: LEK, tovarna farmacevtskih in kemicnih izdelkov, n.sol.o.
    Inventors: Ljubo Antoncic, Iztok Jazbec, Darko Kocjan, Ivana Krivec
  • Patent number: 4766213
    Abstract: Compounds of the formula ##STR1## are disclosed wherein the variables are herein described. These compounds are intermediates to compounds which influence the influx of calcium into the cell.
    Type: Grant
    Filed: January 16, 1987
    Date of Patent: August 23, 1988
    Assignee: Merck Patent Gesellschaft mit beschrankter Haftung
    Inventors: Horst Juraszyk, Rolf Gericke, Inge Lues, Rolf Bergmann, Claus J. Schmitges
  • Patent number: 4761420
    Abstract: Compound of formula 1 are calcium entry antagonists useful for treating hypertension, congestive heart failure, angina, and vasospastic disorders: ##STR1## wherein n is an integer from 1 to 4;R.sub.1 and R.sub.2 are lower alkyl;R.sub.3 is lower alkyl or alkoxyalkyl;A is alkylene of two to eight carbon atoms;X.sub.1 and X.sub.2 are each independently --NO.sub.2, --CF.sub.3, CH.sub.3 O--, --CN, --H, lower alkyl or halo;Y is --O--, --S--, --S(O)--, or --S(O).sub.2 --; andR is H, lower alkyl, cycloalkyl, alkoxyalkyl, cycloalkyloxy-alkyl, alkoxycycloalkyl, acyl, or saturated or unsaturated 5- or 6-membered heterocyclyl optionally substituted with lower alkyl or alkoxy, wherein the heteroatom is one oxygen atom.
    Type: Grant
    Filed: June 13, 1986
    Date of Patent: August 2, 1988
    Assignee: Laboratoires Syntex S.A.
    Inventor: Gilles Genain
  • Patent number: 4758669
    Abstract: Novel nitrone substituted 4-aryl dihydropyridines of the formula: ##STR1## are described along with a process for their preparation. The compounds exhibit calcium channel blocker and antimetastatic acitivity.
    Type: Grant
    Filed: May 5, 1986
    Date of Patent: July 19, 1988
    Assignee: Radiation Oncology Center Research and Development Corporation
    Inventors: Carl R. Johnson, John D. Taylor, Kenneth V. Honn, Soan Cheng
  • Patent number: 4755512
    Abstract: A series of 1,4-dihydropyridin-3,5-yl dicarboxylic acid amides and esters incorporating an arylpiperazinylalkyl moiety have been prepared possessing the general formula ##STR1## wherein R.sup.4 is cycloalkyl, aryl or hetaryl, generally with electronwithdrawing substituents; R.sup.2 and R.sup.6 are lower alkyl, alkanol, alkoxyalkyl, or alkylaminoalkyl; R.sup.5 is R.sup.2 or arylpiperazinylalkyl; X is 0 or NH; Y is lower alkylene, alkoxyalkylene, alkylaminoalkylene; and Z is phenyl, substituted phenyl, pyridinyl, substituted pyridinyl, or pyrimidinyl. Compounds of this series demonstrate activity as calcium and alphaadrenergic blockers in in vitro testing and antihypertensive, antiischemic, and platelet function inhibiting actions in in vivo screens.
    Type: Grant
    Filed: January 22, 1985
    Date of Patent: July 5, 1988
    Assignee: Bristol-Myers Company
    Inventors: Graham Poindexter, Davis L. Temple, Jr.
  • Patent number: 4754033
    Abstract: A process for producing pyridine-2,3-dicarboxylic acid derivatives of the formula ##STR1## is described. The process is based on the cleavage of HNR.sub.10 R.sub.11 from 1-amino-1,2,3,4-tetrahydropyridine-2,3-dicarboxylic acid derivatives of the formula II ##STR2## to give 1,4-dihydropyridine-2,3-dicarboxylic acid derivatives of the formula III ##STR3## and subsequent oxidation of these compounds to obtain pyridine-2,3-dicarboxylic acid derivatives of the formula I. According to one variant of the process, the 1,4-dihydropyridine-2,3-dicarboxylic acid derivatives of the formula III are obtained directly, without isolation of the intermediately formed 1-amino-1,2,3,4-tetrahydropyridine-2,3-dicarboxylic acid derivatives of the formula II, by reaction of .alpha.,.beta.-unsaturated hydrazones of the formula IV ##STR4## with ethene-1,2-dicarboxylic acid derivatives of the formula V ##STR5## and subsequently oxidized to pyridine-2,3-dicarboxylic acid derivatives of the formula I. In the above formulae, R.sub.1, R.
    Type: Grant
    Filed: August 2, 1985
    Date of Patent: June 28, 1988
    Assignee: Ciba-Geigy Corporation
    Inventor: Adrian Waldner
  • Patent number: 4748244
    Abstract: The invention relates to a process for the preparation of pyridine-2,3-dicarboxylic acid derivatives of formula ##STR1## which process comprises reacting a hydrazone of formula II ##STR2## with a maleic acid derivative of formula III ##STR3## to give a 1-amino-1,4-dihydropyridine-2,3-dicarboxylic acid derivative of formula IV ##STR4## and subsequently removing R.sub.9 R.sub.10 NH. In the above formulae, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.9, R.sub.10 and X are as defined in claim 1. The pyridine-2,3-dicarboxylic acid derivatives of formula I are intermediates for the preparation of herbicidal compounds.
    Type: Grant
    Filed: May 3, 1985
    Date of Patent: May 31, 1988
    Assignee: Ciba-Geigy Corporation
    Inventors: Adrian Waldner, Achim Roloff, Daniel Bellus
  • Patent number: 4745123
    Abstract: Certain substituted 1,2,3,6-tetrahydro- and 1,2,5,6-tetrahydropyridine-3-carboxylic acids, esters, and amides possessing muscarinic binding activity, having utility for the treatment of the symptoms of senile cognitive decline disclosed. Pharmaceutical compositions and a pharmaceutical method of treatment are also disclosed.
    Type: Grant
    Filed: February 18, 1986
    Date of Patent: May 17, 1988
    Assignee: Warner-Lambert Company
    Inventors: Donald E. Butler, John H. Dodd, Walter H. Moos, Haile Tecle
  • Patent number: 4732898
    Abstract: The present invention are 2-(2-aryl-2-oxo-alkylidene) analogs of 1,2,3,4-tetrahydropyridine-3,5-pyridinecarboxylic acids and particularly esters thereof having valuable calcium antagonist and positive inotropic activity useful in the treatment of cardiovascular disorders, pharmaceutical compositions and methods of use therefor.
    Type: Grant
    Filed: March 3, 1987
    Date of Patent: March 22, 1988
    Assignee: Warner-Lambert Company
    Inventors: Edward W. Badger, Michael D. Taylor
  • Patent number: 4732985
    Abstract: 1,4-Dihydropyridine anti-ischaemic and antihypertensive agent of the formula: ##STR1## or a pharmaceutically acceptable salt thereof, wherein R is 2-chlorophenyl, 2,3-dichlorophenyl or 2-chloro-3-trifluoromethylphenyl;R.sup.1 and R.sup.2 are each independently C.sub.1 -C.sub.4 alkyl;X is O or S;R.sup.3 is H or C.sub.1 -C.sub.4 alkyl; andR.sup.4 is 1,2,4-triazol-1-ylmethyl, imidazol-1-ylmethyl, azidomethyl, 2,4,5-trimethylimidazol-1-ylmethyl, 3,4-dihydro-4-oxopyrimidin-2-ylthiomethyl, pyrimidin-2-ylthiomethyl; pyrimidin-2-ylaminomethyl, 3,4-dihydro-4-oxopyrimidin-2-ylaminomethyl, 2-aminopyrimidin-4-yloxymethyl, methoxymethyl, 2-furyl, 2-pyridylmethyl, imidazol-2-yl, hydroxymethyl, aminomethyl, 1,2,4-triazol-4-ylmethyl or 2-hydroxyethyl, and intermediates leading thereto.
    Type: Grant
    Filed: November 5, 1986
    Date of Patent: March 22, 1988
    Assignee: Pfizer Inc.
    Inventors: David Alker, Simon F. Campbell, Peter E. Cross
  • Patent number: 4730052
    Abstract: Unsymmetrical 1,4-dihydropyridine-3,5-dicarboxylic acid diesters represented by the general formula ##STR1## wherein R.sup.1 and R.sup.2 are different and represent each a nitratoalkyl having 2 or 3 carbon atoms, are prepared from the corresponding acid monoester in the presence of an organic acid anhydride activating agent. These compounds are useful as therapeutic agents for cardiovascular disorders.
    Type: Grant
    Filed: July 9, 1985
    Date of Patent: March 8, 1988
    Assignee: Taisho Pharmaceutical Co., Ltd.
    Inventors: Yoshimoto Nakashima, Toshihisa Ogawa, Atsuro Nakazato, Yukinari Kumazawa, Kaoru Sota
  • Patent number: 4727066
    Abstract: The preparation of esters of 1,4-dihydropyridine, useful in the prevention and treatment of cardiovascular disorders such as atheroma, of the formula ##STR1## wherein X is a phenyl moiety and Y is piperazine, piperidine or an amide of a benzenecarboxylic acid, is described.
    Type: Grant
    Filed: June 30, 1986
    Date of Patent: February 23, 1988
    Assignee: Cermol S.A.
    Inventors: Carlos E. Sunkel, Miguel Fau de Casa-Juana, Peter R. Statkow, Danielle Straumann
  • Patent number: 4727082
    Abstract: A dihydropyridine compound of the following general formula (I) or a salt thereof: ##STR1## wherein R.sup.1 and R.sup.2, which are the same or different, each represents a C.sub.1 to C.sub.10 alkyl group, a lower alkyl group which is interrupted by oxygen atom(s), or a lower alkyl group substituted by C.sub.3 to C.sub.6 alicyclic group(s); R.sup.3 and R.sup.4, which are the same or different, each represents a lower alkyl group; R.sup.5 and R.sup.6, which are the same or different, each represents a hydrogen atom, a nitro group, a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfonyl group, or a lower alkylsulfinyl group; R.sup.7 and R.sup.8, which are the same or different, each represents a hydrogen atom, a halogen atom, a cyano group, a lower alkoxy group, or a lower alkanoylamino group, or R.sup.7 may combine with R.sup.8 to form a naphthyl group together with the adjacent phenyl group; A represents a single bond, a vinylene group (--CH.dbd.
    Type: Grant
    Filed: September 17, 1986
    Date of Patent: February 23, 1988
    Assignee: Yamanouchi Pharmaceutical Co., Ltd.
    Inventors: Takashi Fujikura, Noriki Ito, Yuzo Matsumoto, Yasuo Isomura, Masaharu Asano, Toichi Takenaka
  • Patent number: 4723014
    Abstract: The present invention provides a process for preparing a 2-substituted-1,4-dihydropyridine by providing a regiospecific bromine containing intermediate which is then reacted with a nucleophile to provide a wide range of substituents at the 2-position of 1,4-dihydropyridines. Also the present invention is novel 3-substituted-1,4-dihydropyridines having cardiovascular activity.
    Type: Grant
    Filed: November 19, 1986
    Date of Patent: February 2, 1988
    Assignee: Warner-Lambert Company
    Inventors: Kevin R. Anderson, Ila Sircar
  • Patent number: 4722931
    Abstract: The invention concerns a compound of the formula ##STR1## and salts thereof resulting from addition with pharmaceutically acceptable mineral or organic acid, wherein R is an alkylenedioxy group substituted at the 2',3'-position, and R.sub.1 and R.sub.2 are selected from the group consisting of a linear or branched alkyl having 1-4 carbon atoms, a methoxyethyl, or a 2-pyridyl methyl group. The compounds of the present invention are useful in relaxing cardiac or smooth muscle.
    Type: Grant
    Filed: June 17, 1986
    Date of Patent: February 2, 1988
    Assignee: Laboratorios Delagrange
    Inventors: Maria J. Verde Casanova, Joaquin A. Galiano Ramos
  • Patent number: 4723011
    Abstract: Pyridine-2,3-dicarboxylates of Formula I ##STR1## are prepared by reacting an alpha halo-beta keto ester of formula II ##STR2## with an alpha, beta-unsaturated aldehyde or ketone of formula III ##STR3## in the presence of a minimum of 2 molar equivalents of ammonium salt.
    Type: Grant
    Filed: October 28, 1985
    Date of Patent: February 2, 1988
    Assignee: American Cyanamid Company
    Inventor: Robert F. Doehner, Jr.
  • Patent number: 4721708
    Abstract: Novel N-substituted tetrahydropyridine compounds are disclosed. The compounds have the property of inhibiting calcium induced contraction of smooth muscle and are adaptable to being employed in the chemotherapeutic treatment of cardiovascular diseases.
    Type: Grant
    Filed: November 26, 1985
    Date of Patent: January 26, 1988
    Assignee: Merck & Co., Inc.
    Inventors: George D. Hartman, Brian T. Phillips
  • Patent number: 4705794
    Abstract: Pyridinecarboxylic acid esters of the formula ##STR1## in which R is an optionally substituted aryl or heterocyclic radical,R.sup.1 and R.sup.2 are hydrogen, alkyl, aryl, aralkyl, acyloxyalkyl or hydroxyalkyl, or R.sup.1 with X forms a carbonyl-containing heterocyclic ring,X is --CN, --CO--R.sup.4, --COOR.sup.5 or --SO.sub.2 R.sup.6,R.sup.4, R.sup.5 and R.sup.6 are various optionally substituted radicals, andR.sup.3 is different from R.sup.5 and is a substituted or interrupted hydrocarbon radical,or pharmaceutically acceptable salts thereof control the otherwise negative effects of ischaemia and/or hypoxia.
    Type: Grant
    Filed: February 28, 1983
    Date of Patent: November 10, 1987
    Assignee: Bayer Aktiengesellschaft
    Inventors: Egbert Wehinger, Horst Meyer, Ulrich Benz
  • Patent number: 4705797
    Abstract: Novel antihypertensive and coronary dilating asymmetric diesters of 1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylic acid (or the stereoisomers or pharmaceutically acceptable acid addition salts thereof) have the general formula (I): ##STR1## wherein Ph is phenyl, Ar is 2-nitrophenyl, 3-nitrophenyl, 2,3-dichlorophenyl or benzofurazan-4-yl, A is a straight or branched chain alkylene radical having from 2 to 6 carbon atoms, R is a straight or branched chain alkyl radical having from 1 to 6 carbon atoms, optionally mono-substituted by an alkoxy substituent having from 1 to 6 carbon atoms, R.sub.1 is hydrogen, hydroxy or an alkyl radical having from 1 to 4 carbon atoms, and R.sub.2 is hydrogen or methyl. The subject diesters are facilely prepared from the aldehydes ArCHO and esters of acetoacetic and 3-aminocrotonic acids.
    Type: Grant
    Filed: February 14, 1985
    Date of Patent: November 10, 1987
    Assignee: Recordati S.A., Chemical and Pharmaceutical Company
    Inventors: Dante Nardi, Amedeo Leonardi, Gabriele Graziani, Giorgio Bianchi
  • Patent number: 4703119
    Type: Grant
    Filed: June 4, 1985
    Date of Patent: October 27, 1987
    Assignee: Bayer Aktiengesellschaft
    Inventors: Egbert Wehinger, Horst Meyer
  • Patent number: 4692184
    Abstract: There are disclosed novel 2,6-substituted-3,5-pyridinedicarboxylic acids, esters, salts, amides, halides, and cyano compounds useful as herbicides, and as intermediates which provide herbicides.
    Type: Grant
    Filed: April 24, 1984
    Date of Patent: September 8, 1987
    Assignee: Monsanto Company
    Inventor: Len F. Lee
  • Patent number: 4686217
    Abstract: There are described compounds of formula I, ##STR1## in which R.sub.1 represents benzofurazanyl, pyridyl or phenyl, the pyridyl or phenyl being substituted,--COOR.sub.2 and --COOR.sub.3 are various ester groups,one of R.sub.7 and R.sub.8 represents alkyl Cl to 6 and the other represents --CONR.sub.10 R.sub.11 ; --CSNH.sub.2 ; --C(.dbd.NH)SR.sub.9 ; --S(O).sub.m R.sub.9 ; phenyl optionally substituted by one or more of alkyl Cl to 6, halogen, alkoxy Cl to 6 or nitro; alkyl Cl to 6 substituted by halogen; or furanyl;m is 0 or 1R.sub.9 is alkyl Cl to 6, andR.sub.10 and R.sub.11 each independently represent hydrogen or alkyl Cl to 6, or together with the nitrogen atom to which they are attached form a 5 or 6 membered heterocyclic ring.There are also described processes for making the compounds, and pharmaceutical, e.g. calcium antagonist, formulations containing them.
    Type: Grant
    Filed: April 17, 1984
    Date of Patent: August 11, 1987
    Assignee: Fisons plc
    Inventors: Andrew J. G. Baxter, John Dixon, Kenneth J. Gould, Alan C. Tinker
  • Patent number: 4683310
    Abstract: Metal values are extracted from aqueous solutions of metal salts containing halide or pseudo halide ions by pyridine derivatives containing the substituent --(COX).sub.A where X is the group --OR.sub.1 or --NR.sub.2 R.sub.3 and n is 1, 2 or 3. R.sub.1 is a hydrocarbyl group containing from 5 to 36 carbon atoms and R.sub.2 and R.sub.3 are hydrogen or a hydrocarbyl group wherein R.sub.2 and R.sub.3 together contain from 5 to 36 carbon atoms. The process is especially useful for the recovery of metals from leach solutions derived from sulphur-containing ores such as chalcopyrite.
    Type: Grant
    Filed: February 19, 1985
    Date of Patent: July 28, 1987
    Assignee: Imperial Chemical Industries, PLC
    Inventors: Raymond F. Dalton, Raymond Price, Peter M. Quan, David Stewart
  • Patent number: 4678796
    Abstract: Novel 2-(2-alkoxy-2-oxoethylidene)-1,2,3,4-tetrahydro-6-methyl-4-[2-(substituted )phenyl]-3,5-pyridinedicarboxylic acid dialkyl ester derivatives having novel inotropic and hypotensive activity, processes for their manufacture, pharmaceutical compositions, and methods for using said compounds and compositions are described.
    Type: Grant
    Filed: September 3, 1986
    Date of Patent: July 7, 1987
    Assignee: Warner-Lambert Company
    Inventors: Michael D. Taylor, Edward W. Badger
  • Patent number: 4675329
    Type: Grant
    Filed: June 27, 1985
    Date of Patent: June 23, 1987
    Assignee: Bayer Aktiengesellschaft
    Inventors: Egbert Wehinger, Andreas Knorr, Kurt Stoepel, Arend Heise
  • Patent number: 4672071
    Abstract: Compositions containing dihydropyridine derivatives which are useful for treating congestive heart failure, hypertension, or angina have the formula: ##STR1## or a pharmaceutically acceptable acid addition salt thereof, wherein n is an integer from 0 to 8;Y is --O--, --NH--, --NR.sub.2 --, --S--, --S(O)--, --S(O).sub.2 --, or a bond;R.sub.1 and R.sub.2 are each independently A.sub.1, A.sub.2, A.sub.3 or A.sub.4 whereA.sub.1 is --(CH.sub.2).sub.m (CHOH).sub.p CH.sub.2 OH;A.sub.2 is --(CH.sub.2).sub.q CH.sub.(3-r) [(CH.sub.2).sub.s OH].sub.r ;A.sub.3 is --(CH.sub.2).sub.q CH.sub.(3-r) [(CH.sub.2).sub.p COOR.sub.3 ].sub.r ; andA.sub.4 is --(CH.sub.2).sub.m COOR.sub.3 ; wherem is an integer from 1 to 8;p is an integer from 0 to 4;q is an integer from 0 to 8;r is 2 or 3;s is an integer from 1 to 4; andR.sub.3 is H or alkyl of 1 to 18 carbon atoms;R.sub.4 is --NO.sub.2, --CF.sub.3, or halo; andR.sub.5 is lower alkyl or --CH.sub.2 CH.sub.2 OCH.sub.3.
    Type: Grant
    Filed: December 12, 1985
    Date of Patent: June 9, 1987
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Robin D. Clark, Moysey M. Povzhitkov
  • Patent number: 4672068
    Abstract: 1,4-dihydropyridine derivatives represented by the following general formula, ##STR1## in which R.sup.3 is a combination of an unsaturated straight chain hydrocarbon group or derivative thereof connected by a single bond with an unsaturated hydrocarbon group or derivative thereof so that the unsaturated carbon atoms of the two groups are in conjugated relationship. These compounds have a hypotensive action the effective time of which is long, which makes the blood pressure descend slowly, and the toxicity of which is low.
    Type: Grant
    Filed: April 26, 1985
    Date of Patent: June 9, 1987
    Assignee: Fujirebio Kabushiki Kaisha
    Inventors: Teruo Kutsuma, Hiroshi Ikawa, Yoshiaki Sato
  • Patent number: 4656181
    Abstract: New esters of 1,4-dihydropyridine (and their salts) are prepared which are useful as pharmacologically active ingredients in particular in medicaments for the preventive and curative treatment of cardiovascular disorders.Said esters have for formula ##STR1## where R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, X and Y and index n are defined as in claim 1.
    Type: Grant
    Filed: July 20, 1984
    Date of Patent: April 7, 1987
    Assignee: Cermol S.A.
    Inventors: Carlos E. Sunkel, Miguel Fau de Casa-Juana, Peter R. Statkow, Danielle Straumann
  • Patent number: 4654353
    Abstract: Compounds of the formula: ##STR1## where R is an optionally substituted aryl or heteroaryl group;R.sup.1 and R.sup.2 are each independently C.sub.1 -C.sub.4 alkyl or 2-methoxyethyl; and Y is --(CH.sub.2).sub.n -- where n is 2, 3 or 4, --CH.sub.2 CH(CH.sub.3)-- or --Ch.sub.2 C(CH.sub.3).sub.2 --; and their pharmaceutically acceptable salts.The compounds have utility as anti-ischaemic and antihypertensive agents and as synthetic intermediates to other dihydropyridine calcium antagonists.
    Type: Grant
    Filed: April 26, 1985
    Date of Patent: March 31, 1987
    Assignee: Pfizer Inc.
    Inventors: David Alker, Simon F. Campbell, Peter E. Cross
  • Patent number: 4647565
    Abstract: Dihydropyridines of the formulae ##STR1## wherein R is chlorothienyl or mono- or disubstituted phenyl where said substituent is fluoro, chloro, bromo or trifluoromethyl; R.sup.1 and R.sup.2 are each alykl; R.sup.3 and R.sup.4 when taken separately are each hydrogen or alkyl; R.sup.3 and R.sup.4 when taken together with the nitrogen to which they are attached are piperidine or pyrrolidine; R.sup.5 is alkyl or 2-hydroxyethyl; R.sup.6 is hydrogen or methoxy; X and Z are each hydrogen or methoxy; Y is alkylene; R.sup.7 is chlorophenyl or trifluoromethyl-chlorophenyl; p is 0 or 1; and Q is CH or N are useful in the treatment of hypertension, heart failure and angina.
    Type: Grant
    Filed: June 5, 1985
    Date of Patent: March 3, 1987
    Assignee: Pfizer Inc.
    Inventors: John E. Arrowsmith, Simon F. Campbell, Peter E. Cross, Roger P. Dickinson
  • Patent number: 4647691
    Abstract: Ethyl and n-propyl esters of carboxylic acids are prepared in good yield from methanol, syngas and a carboxylic acid by contacting a mixture of the carboxylic acid, carbon monoxide, hydrogen and methanol with a catalyst composition comprising a ruthenium-containing compound, a cobalt-containing compound and a quaternary onium salt or base, and heating the resulting mixture at an elevated temperature and pressure for sufficient time to produce the desired ethyl and propyl esters, and then recovering the same from the reaction mixture.
    Type: Grant
    Filed: January 13, 1982
    Date of Patent: March 3, 1987
    Assignee: Texaco Inc.
    Inventors: Jiang-Jen Lin, John F. Knifton
  • Patent number: 4634712
    Type: Grant
    Filed: May 14, 1985
    Date of Patent: January 6, 1987
    Assignee: Recordati S.A.
    Inventors: Dante Nardi, Amedeo Leonardi, Giorgio Bianchi
  • Patent number: 4631081
    Abstract: The invention concerns novel compounds of the formula I ##STR1## wherein: Z is selected from oxygen and the group --YAn wherein Y is selected from C.sub.1 to C.sub.6 alkyl and benzyl and An is an anion;k is zero or the integer 1;n is an integer selected from 3 and 4;X is selected from halogen, nitro, cyano, alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, alkenyl, alkenyloxy, alkynyl, alkynyloxy, acyloxy, alkoxycarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl, sulfamoyl, substituted sulfamoyl, alkanoyloxy, benzyloxy, substituted benzyloxy, amino, substituted amino and the groups formyl and alkanoyl and the oxime, imine and Schiff base derivatives thereof;R.sup.1 is selected from hydrogen, alkyl, alkenyl, alkynyl, substituted alkyl, alkylsulfonyl, arylsulfonyl, acyl and an inorganic or organic cation;R.sup.2 is selected from alkyl, substituted alkyl, alkenyl, haloalkenyl, alkynyl and haloalkynyl;R.sup.3 is selected from alkyl, fluoroalkyl, alkenyl, alkynyl, and phenyl; andR.sup.
    Type: Grant
    Filed: September 27, 1983
    Date of Patent: December 23, 1986
    Assignee: ICI Australia Limited
    Inventors: Keith G. Watson, Graham J. Bird, Graeme J. Farquharson, Richard J. Conway, Peter G. Tucker
  • Patent number: 4622332
    Abstract: Compounds of the formula ##STR1## in which R is an optionally substituted aryl or heterocyclic radical,R.sup.1 is a hydrocarbon radical which is optionally interrupted by 1 oxygen atom in the chain, and/or which is optionally substituted,R.sup.4 is an aliphatic hydrocarbon radical having 7 to 14 carbon atoms, which is optionally interrupted by one oxygen atom and/or which is optionally substituted,R.sup.2 and R.sup.3 each independently is hydrogen, an alkyl radical, an aryl radical or an aralkyl radical, or, for the case where one of the substituents R.sup.2 or R.sup.3 has the above-mentioned meaning, the other is hydroxymethyl, acetoxymethyl or amino, andX is N-R.sup.5, wherein R.sup.5 is hydrogen, an alkyl radical which is optionally interrupted by an oxygen atom, a morpholinoalkyl radical, an aryl radical or an aralkyl radical orX is an oxygen atom, when one of the radicals R.sup.2 or R.sup.3 denotes an amino group,or pharmaceutically acceptable acid addition salts thereof, exhibit hypotensive activity.
    Type: Grant
    Filed: February 22, 1983
    Date of Patent: November 11, 1986
    Assignee: Bayer Aktiengesellschaft
    Inventors: Egbert Wehinger, Horst Meyer, Andreas Knorr