Patents by Inventor George Y. Lesher
George Y. Lesher has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
-
Patent number: 4298609Abstract: 4,5-Dihydro-6-(4-pyridinyl)-3-pyridazinol or pharmaceutically-acceptable acid-addition salt thereof is useful as a blood pressure lowering agent. 4,5-Dihydro-6-(4-pyridinyl)-3-pyridazinol is prepared by reacting .gamma.-oxo-.gamma.-(4-pyridinyl)butyronitrile with a hydrazine salt of a strong inorganic or organic sulfonic acid. Said 4,5-dihydro-6-(4-pyridinyl)-3-pyridazinol or pharmaceutically-acceptable salt thereof is shown as the active ingredient in pharmaceutical compositions for lowering blood pressure and in the method for lowering blood pressure in a patient having elevated blood pressure.Type: GrantFiled: August 30, 1979Date of Patent: November 3, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, William B. Dickinson
-
Patent number: 4297363Abstract: 2-Amino-3(4 or 5)-PY-phenol, a cardiotonic agent, is prepared by reducing 2-nitro-3(4 or 5)-PY-phenol, where PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. 2-Amino-3(4 or 5)-PY-phenol or pharmaceutically-acceptable acid-addition salt thereof is disclosed as the active component in a cardiotonic composition for increasing cardiac contractility and in the method for increasing cardiac contractility in a patient requiring such treatment. The novel isomeric 4-amino-5-(4-pyridinyl)phenol is shown for comparative purposes.Type: GrantFiled: July 21, 1980Date of Patent: October 27, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Baldev Singh
-
Patent number: 4297362Abstract: 4-(3,4-Diaminophenyl)pyridine, a cardiotonic agent, is prepared by reducing 4-(4-amino-3-nitrophenyl)pyridine or preferably by reacting 4-(4-acetylamino-3-nitrophenyl)pyridine or 4-(3-acetylamino-4-nitrophenyl)pyridine with stannous chloride and hydrochloric acid. 4-(3,4-diaminophenyl)pyridine or pharmaceutically-acceptable acid-addition salt thereof is disclosed as the active ingredient in a cardiotonic composition for increasing cardiac contractility and in the method for increasing cardiac contractility in a patient requiring such treatment.Type: GrantFiled: July 28, 1980Date of Patent: October 27, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Baldev Singh
-
Patent number: 4297360Abstract: 2-R.sub.3 RN-3-R.sub.1 R'N-5-PY-6-Q-pyridines (I) or pharmaceutically-acceptable acid-addition salts thereof are useful as intermediates in the preparation of 1- or 3-substituted-1,3-dihydro-5-Q-6-PY-2H-imidazo[4,5-b]pyridin-2-ones or -2-thiones and also as intermediates for preparing 1- or 3-substituted-5-Q-6-PY-3H(or 1H)-imidazo[4,5-b]pyridines, where R.sub.1, R.sub.3, R, R', PY and Q are defined hereinbelow. Also shown are processes for preparing I and the following intermediates used therein: 2-halo-3-nitro-5-PY-6-Q-pyridines (III), 2-R.sub.3 RN-3-nitro-5-PY-6-Q-pyridines (V), 2-halo-5-PY-6-Q-pyridines (VII), 2-R.sub.3 RN-5-PY-6-Q-pyridines (VIII) and 2-R.sub.3 RN-3-halo-5-PY-6-Q-pyridines (IX) or salts thereof. Certain embodiments of II and VIII also are useful as cardiotonics and are shown as active components of cardiac compositions and methods for increasing cardiac contractility.Type: GrantFiled: March 28, 1980Date of Patent: October 27, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr., Donald F. Page
-
Patent number: 4294836Abstract: 1,3-Dihydro-3-R-5-PY-2H-imidazo[4,5-b]pyridin-2-ones or 2-thiones or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonic agents, where R is hydrogen, lower-alkyl, lower-hydroxyalkyl, 2,3-dihydroxypropyl, lower-alkoxyalkyl or Y-NB where Y is lower-alkylene and NB is di-(lower-alkyl)amino or 4-morpholinyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, are prepared by reacting a 3-amino-2-RNH-6-PY-pyridine with urea or carbonyldiimidazole to produce said -2-ones or with an alkali metal xanthate, thiourea or thiocarbonyldiimidazole to produce said -2-thiones. Also shown is the preparation of the intermediate 3-amino-2-RNH-6-PY-pyridines.Type: GrantFiled: March 24, 1980Date of Patent: October 13, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Ruth P. Brundage
-
Patent number: 4294837Abstract: 1,3-Dihydro-1-R.sub.1 -3-R.sub.3 -6-PY-5-Q-2H-imidazo[4,5-b]pyridin-2-ones or -2-thiones or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonic agents, where Q is hydrogen or lower-alkyl, R.sub.1 and R.sub.3 are each hydrogen, lower-alkyl, lower-hydroxyalkyl, 2,3-dihydroxypropyl, lower-alkoxyalkyl or Y-NB where Y is lower-alkylene and NB is di-(lower-alkyl)amino or 4-morpholinyl, at least one of R.sub.1 and R.sub.3 being hydrogen, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two substituents, are prepared by reacting a 2-R.sub.3 NH-3-R.sub.1 NH-5-PY-6-Q-pyridine with urea or carbonyldiimidazole to produce said -2-one or with an alkali metal xanthate, thiourea or thiocarbonyldiimidazole to produce said -2-thione. Also shown and claimed are cardiotonic compositions and a method for increasing cardiac contractility using said cardiotonic agents. Also shown are processes for preparing said intermediate 2-R.sub.3 NH-3-R.sub.Type: GrantFiled: March 28, 1980Date of Patent: October 13, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr., Donald F. Page
-
Patent number: 4276293Abstract: 2-R.sub.2 -3-R.sub.3 -6-PY-5-Q-3H-imidazo[4,5-b]pyridines (I) or 1-R.sub.1 -2-R.sub.2 -6-PY-5-Q-1H-imidazo[4,5-b]pyridines (IA) or pharmaceutically-acceptable acid-addition salts thereof, where Q and R.sub.2 are each hydrogen or lower-alkyl, R.sub.1 and R.sub.3 are each hydrogen, lower-alkyl, lower-hydroxyalkyl, 2,3-dihydroxypropyl, lower-alkoxyalkyl or Y-NB where Y is lower-alkylene having at least two carbon atoms between its connecting linkages and NB is di-(lower-alkyl)amino or 4-morpholinyl, at least one of R.sub.1 or R.sub.3 being hydrogen, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, which are useful as cardiotonics, are prepared by reacting 2-R.sub.3 NH-3-R.sub.1 NH-5-PY-6-Q-pyridine (II) with a tri-(lower-alkyl) ortho-(lower-alkanoate). Also shown are: the use of I or IA or salts in cardiotonic compositions and a method for increasing cardiac contractility; and, the preparation of the intermediates II, as well as intermediates used to prepare II.Type: GrantFiled: March 28, 1980Date of Patent: June 30, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr., Donald F. Page
-
Patent number: 4271168Abstract: 3-Acylamino-5-[4(or 3)-pyridinyl]-2(1H)-pyridinones or pharmaceutically-acceptable acid-addition salts thereof useful as cardiotonic agents are prepared by reacting the corresponding 3-amino compound with an acylating agent providing acyl, where acyl is 2-acetoxypropanoyl, acetoacetyl or acetoxyacetyl. Cardiotonic compositions and method for increasing cardiac contractility using said 3-acylamino compounds as active component are disclosed.Type: GrantFiled: December 26, 1979Date of Patent: June 2, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr.
-
Patent number: 4265895Abstract: 1,2-Dihydro-1-R-5-PY-6-Q-3H-pyrazolo[3,4-b]pyridin-3-ones or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonic agents, are prepared by reacting lower-alkyl 2-halo-5-PY-6-Q-nicotinate with 1-R-hydrazine. Also disclosed are cardiotonic compositions and method for increasing cardiotonic contractility using said compounds or salts.Type: GrantFiled: March 17, 1980Date of Patent: May 5, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Monte D. Gruett
-
Patent number: 4264612Abstract: Cardiotonic composition and method for increasing cardiac contractility using an effective amount of a cardiotonic lower-alkyl 2-halo-5-PY-6-Q'-nicotinate or pharmaceutically-acceptable acid-addition salt thereof, where halo is chloro or bromo, Q' is hydrogen or lower-alkyl and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. Also shown are novel lower-alkyl 2-halo-5-PY-6-(lower-alkyl)nicotinates or pharmaceutically-acceptable acid-addition salt thereof, useful as intermediates or cardiotonics and preparation thereof.Type: GrantFiled: March 17, 1980Date of Patent: April 28, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Monte D. Gruett
-
Patent number: 4264603Abstract: 1-R-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridin-3-amines or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonics, are prepared by reacting a 2-halo-5-PY-6-Q-nicotinonitrile with 1-R-hydrazine, where R is hydrogen, lower-alkyl, lower-hydroxyalkyl, 2,3-dihydroxypropyl or lower-alkoxyalkyl, Q is hydrogen or lower-alkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. Also shown are cardiotonic compositions and method for increasing cardiac contractility using said compounds or salts.Type: GrantFiled: March 17, 1980Date of Patent: April 28, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Monte D. Gruett
-
Patent number: 4225715Abstract: Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or .alpha.-PY-malonaldehyde (II') with .alpha.Type: GrantFiled: June 20, 1979Date of Patent: September 30, 1980Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr.
-
Patent number: 4225601Abstract: 3-(Hydroxy or hydroxymethyl)-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof is useful as a cardiotonic agent. 3-Hydroxy-5-(4-pyridinyl)-2(1H)-pyridinone is prepared by autoclaving a mixture of an alkali lower-alkoxide, loweralkanol and 3-halo-5-(4-pyridinyl)-2(1H)-pyridinone and acidifying the cooled reaction mixture. 3-Hydroxymethyl-5-(4-pyridinyl)-2(1H)-pyridinone is prepared by reacting 5-(4-pyridinyl)-2(1H)-pyridinone with excess formaldehyde at an acidic pH. Said 3-(hydroxy or hydroxymethyl)-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof is disclosed as the active ingredient in cardiotonic compositions for increasing cardiac contractility and in the method for increasing cardiac contractility in a patient requiring such treatment.Type: GrantFiled: September 10, 1979Date of Patent: September 30, 1980Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr.
-
Patent number: 4223149Abstract: A process for preparing 1,2-dihydro-2-oxo-5-(pyridinyl) nicotinonitriles by reacting .alpha.-(pyridinyl)-.beta.-[di-(lower-alkyl)amino]acrolein with malononitrile in a lower-alkanol. The products are useful as cardiotonic agents and, also, as intermediates for preparing corresponding 3-amino-5-(pyridinyl-2(1H)-pyridinones, in turn, useful as cardiotonic agents.Type: GrantFiled: July 26, 1979Date of Patent: September 16, 1980Assignee: Sterling Drug Inc.Inventors: Chester J. Opalka, Jr., George Y. Lesher
-
Patent number: 4199586Abstract: Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or .alpha.-PY-malonaldehye (II') with .alpha.Type: GrantFiled: August 28, 1978Date of Patent: April 22, 1980Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr.
-
Patent number: 4137233Abstract: Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or .alpha.-PY-malonaldehyde (II') with .alpha.Type: GrantFiled: February 10, 1978Date of Patent: January 30, 1979Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr.
-
Patent number: 4137227Abstract: Compounds useful as antibacterial agents are 1-R-1,4-dihydro-4-oxo-7-(BN--N.dbd.N)-3-quinolinecarboxylic acids (I), wherein: (a) BN is dimethylamino where R is methyl, ethyl, n-propyl, n-butyl, n-pentyl or n-octyl; (b) BN is diethylamino where R is n-propyl; or, (c) BN is 4-methyl-1-piperazinyl where R is ethyl. These compounds are prepared by reacting lower-alkyl 7-amino-1-R-1,4-dihydro-4-oxo-3-quinolinecarboxylate (II) with a mineral acid and an alkali nitrite in aqueous medium to produce the corresponding diazonium salt of said 7-aminoquinoline, reacting said diazonium salt with an amine of the formula BNH in the presence of an acid-acceptor to produce lower-alkyl 1-R-1,4-dihydro-4-oxo-7-(BN--N.dbd.N)-3-quinolinecarboxylate and hydrolyzing said 3-quinolinecarboxylate to produce the corresponding 3-carboxylic acid (I). The intermediate lower-alkyl 7-amino-1-R-1,4-dihydro-4-oxo-3-quinolinecarboxylate (II) are prepared in several steps by conventional means starting with m-aniline.Type: GrantFiled: August 29, 1977Date of Patent: January 30, 1979Assignee: Sterling Drug Inc.Inventors: Andrew W. Zalay, George Y. Lesher
-
Patent number: 4118557Abstract: Cyclic alkylidenyl N-(lower-alkyl)-3-PY-anilinomethylenemalonates (I), where PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, are prepared by reacting cyclic alkylidenyl (lower-alkoxy)methylenemalonate (II) with N-(lower-alkyl)-3-PY-aniline (III). Also, I is heated with polyphosphoric acid to produce 1-(lower-alkyl)-1,4-dihydro-4-oxo-7-PY-3-quinolinecarboxylic acid, known antibacterial agents. The N-(lower-alkyl)-3-PY-anilines are produced by reducing the corresponding N-(3-PY-phenyl)-(lower-alkanamides).Type: GrantFiled: July 28, 1977Date of Patent: October 3, 1978Assignee: Sterling Drug Inc.Inventor: George Y. Lesher
-
Patent number: 4118571Abstract: Compounds useful as anti-allergic agents are 2-Q-4-[XZC.dbd.C(R)NH]-5-R.sub.1 -6-R.sub.2 -pyrimidines (I), where Q is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents or N-oxide thereof, R is hydrogen or lower-alkyl, R.sub.1 is hydrogen, lower-alkyl or cyano, R.sub.2 is hydrogen, lower-alkyl, hydroxy or halo, X and Z are the same or different and are each selected from lower-carbalkoxy, lower-alkanoyl, carbamyl and cyano, or ##STR1## is ##STR2## where R.sub.3 and R.sub.4 are each lower-alkyl, or X is hydrogen, are prepared by reacting 4-amino-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidine (II where Q' is amino) with R'O--C(R).dbd.CXZ (III). Preparations of II are given. Also shown as intermediates and/or anti-allergic agents are 4-(AcNH)-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidines (IV) and 4-(R.sub.5 R.sub.6 N)-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidines (V) where Ac is lower-alkanoyl or lower-carbalkoxy, R.sub.5 is hydrogen, lower-alkyl or lower-hydroxyalkyl, and R.sub.Type: GrantFiled: November 30, 1977Date of Patent: October 3, 1978Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Baldev Singh
-
Patent number: RE30024Abstract: Compounds useful as anti-allergic agents are 2-Q-4-[XZC.dbd.C(R)NH]-5-R.sub.1 -6-R.sub.2 -pyrimidines (I), where Q is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents or N-oxide thereof, R is hydrogen or lower-alkyl, R.sub.1 is hydrogen, lower-alkyl or cyano, R.sub.2 is hydrogen, lower-alkyl, hydroxy or halo, X and Z are the same or different and are each selected from lower-carbalkoxy, lower-alkanoyl, carbamyl and cyano, or ##STR1## is ##STR2## where R.sub.3 and R.sub.4 are each lower-alkyl, or X is hydrogen, are prepared by reacting 4-amino-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidine (II where Q' is amino) with R'O--C(R).dbd.CXZ (III). Preparation of II are given. Also shown as intermediates and/or anti-allergic agents are 4-(AcNH)-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidines (IV) and 4-(R.sub.5 R.sub.6 N)-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidines (V) where Ac is lower-alkanoyl or lower-carbalkoxy, R.sub.5 is hydrogen, lower-alkyl or lower-hydroxyalkyl, and R.sub.Type: GrantFiled: June 5, 1978Date of Patent: June 5, 1979Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Baldev Singh