Patents Represented by Attorney Hans L. Berneis
  • Patent number: 4226772
    Abstract: The compound of the formula ##STR1## wherein R' and R" are alkyl of 1 to 3 carbon atoms, inclusive; wherein R.sub.1 is hydrogen, fluoro, chloro, bromo, nitro, trifluoromethyl or alkylthio in which the alkyl moiety is of 1 to 3 carbon atoms, inclusive; and wherein R.sub.2 is phenyl, o-chlorophenyl, o-fluorophenyl, or 2,6-difluorophenyl, is prepared by reacting a 1-halomethyl-6-phenyl-4H-s-triazo[4,3-a][1,4]-benzodiazepine with N,N-dimethylhydroxylamine and a strong base. The compound II and its pharmacologically acceptable acid addition salts have sedative and tranquilizing activity.
    Type: Grant
    Filed: September 8, 1978
    Date of Patent: October 7, 1980
    Assignee: The Upjohn Company
    Inventor: Jackson B. Hester, Jr.
  • Patent number: 4215117
    Abstract: Stable formulations of ketazolam containing 15 to 100 mg of ketazolam are prepared by admixing the ketazolam with either calcium lactate and a powdered edible vegetable fat or fatty oil, Sterotex.RTM., or with calcium carboxymethylcellulose and Sterotex.RTM..
    Type: Grant
    Filed: May 26, 1978
    Date of Patent: July 29, 1980
    Assignee: The Upjohn Company
    Inventors: Ashok C. Shah, Edward P. Strzelinski
  • Patent number: 4196132
    Abstract: 3,4,5,6-Tetrachloro-3,5-cyclohexadiene-1,2-dione (o-chloranil), a valuable organic oxidant used particularly in the photographic industry, has now been found to be synthesizable by an improved, continuous flow process from catechol.
    Type: Grant
    Filed: August 11, 1978
    Date of Patent: April 1, 1980
    Assignee: The Upjohn Company
    Inventors: Fredric G. Bader, Howard J. Burke
  • Patent number: 4186208
    Abstract: A pharmaceutical formulation containing, as active ingredient, a compound of the Formula III: ##STR1## wherein A is a group selected from --(CH.sub.2).sub.2 --; --(CH.sub.2).sub.3 --; --(CH.sub.2).sub.4 --; --(CH.sub.2).sub.5 --; ##STR2## wherein R is ethyl, vinyl, or cyclopropyl; and wherein X is bromo or chloro, or the pharmacologically acceptable acid addition salts for the treatment of depression in warm-blooded animals, including man.
    Type: Grant
    Filed: January 29, 1979
    Date of Patent: January 29, 1980
    Assignee: The Upjohn Company
    Inventors: Michael P. Kane, Jacob Szmuszkovicz
  • Patent number: 4180522
    Abstract: The present specification provides compounds of the formula: ##STR1## wherein A is a group selected from --(CH.sub.2).sub.2 --; --(CH.sub.2).sub.3 --; --(CH.sub.2).sub.4 --; ##STR2## wherein R is ethyl, vinyl, or cyclopropyl; and wherein X is bromo or chloro. These compounds, including the pharmacologically acceptable salts thereof, are disclosed as useful antidepressant agents in warm-blooded animals, particularly man.
    Type: Grant
    Filed: August 16, 1978
    Date of Patent: December 25, 1979
    Assignee: The Upjohn Company
    Inventors: Michael P. Kane, Jacob Szmuszkovicz
  • Patent number: 4167567
    Abstract: Antihypertensive compounds of the formula ll ##STR1## wherein X is chloro or trifluoromethyl; wherein R is an aromatic heterocyclic radical selected from the group consisting of triazinyl, pyrazinyl, pyridinyl, pyrimidinyl or the above radicals substituted by one or two trifluoromethyl, alkyl, alkoxy, dialkylamino, alkylthio, or halo, or 1 to 4 halo atoms for pyridine, or combinations of substituents, in which alkyl and alkoxy are each of 1 to 3 carbon atoms, inclusive, and halo is fluoro, bromo or chloro, or R is the group ##STR2## in which R.sub.1 is phenyl, phenyl-substituted with one or two halogens, trifluoromethylphenyl, phenyl-substituted with one or two alkoxy or alkyl groups, or alkylphenylsulfonyl, in which alkyl, alkoxy, and halo are defined as above; or R is the group SO.sub.2 R.sub.2, in which R.sub.
    Type: Grant
    Filed: May 5, 1978
    Date of Patent: September 11, 1979
    Assignee: The Upjohn Company
    Inventor: John M. McCall
  • Patent number: 4159331
    Abstract: Antihypertensive compounds for the treatment of hypertensive mammals, including man, of the formula III: ##STR1## wherein X is chloro or trifluoromethyl; wherein R is a radical such as triazinyl, pyrazinyl, pyridinyl, pyrimidinyl, phenyl, or the above radicals substituted by one or two trifluoromethyl, halo, alkyl, alkoxy, dialkylamino or alkylthio groups; or R is the group ##STR2## in which R.sub.1 is phenyl, phenyl substituted with one or two halo atoms, alkoxy or alkyl groups, trifluoromethyl, or R.sub.1 is alkylphenylsulfonyl; or R is the group --SO.sub.2 R.sub.2, in which R.sub.2 is dialkylamino, phenyl, phenyl substituted with halo atoms, alkyl, or alkoxy groups, or trifluoromethyl are prepared from (7-chloro)- or (7-trifluoromethyl)-4-chloroquinoline or 1-[[4-[[(7-chloro)- or (7-trifluoromethyl)quinolinyl]amino]phenyl]sulfonyl]piperazine.
    Type: Grant
    Filed: May 5, 1978
    Date of Patent: June 26, 1979
    Assignee: The Upjohn Company
    Inventor: John M. McCall
  • Patent number: 4141902
    Abstract: 1-Substituted-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines of the formula II: ##STR1## wherein R.sub.0 is selected from the group consisting of hydrogen, methyl, ethyl, fluorine, chlorine, and bromine, and X is selected from fluorine, chlorine, and bromine; wherein R.sub.1 is selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms inclusive; wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are selected from the group consisting of hydrogen, alkyl, as defined above, halogen, nitro, cyano, trifluoromethyl, and alkoxy, alkylthio, alkylsulfinyl, and alkylsulfonyl, in which the carbon chain moieties are of 1 to 3 carbon atoms, inclusive, are prepared by reacting a compound of the formula: ##STR2## wherein R.sub.1, R.sub.2, R.sub.3 R.sub.4, and R.sub.5 are defined as above, with an haloacyl chloride or haloacyl bromide of the formula ##STR3## wherein R.sub.o and X are defined as above and X' is chlorine or bromine.
    Type: Grant
    Filed: April 28, 1971
    Date of Patent: February 27, 1979
    Assignee: The Upjohn Company
    Inventor: Jackson B. Hester, Jr.
  • Patent number: 4140775
    Abstract: Antihypertensive compounds of the formula III ##STR1## wherein X is chloro or trifluoromethyl; wherein R is hydrogen or alkyl of 1 to 3 carbon atoms, inclusive; wherein R.sub.1 is phenyl or phenyl substituted with one or two alkyl, alkoxy, trifluoromethyl or halo substituents, in which alkyl and alkoxy are each of 1 to 3 carbon atoms, inclusive, and halo is fluoro, chloro or bromo, are prepared by reacting a 4-chloro-7-substituted quinoline of formula I with a compound of the formula II ##STR2## wherein R and R.sub.1 are defined as above. The pharmacologically acceptable acid addition salts of compounds of formula III can also be used as antihypertensive agents.
    Type: Grant
    Filed: May 5, 1978
    Date of Patent: February 20, 1979
    Assignee: The Upjohn Company
    Inventor: John M. McCall
  • Patent number: 4107159
    Abstract: Compounds of the formula: ##STR1## wherein R.sub.1 is alkyl of 1 to 3 carbon atoms, inclusive; wherein R.sub.2 is hydrogen, methyl or ethyl; wherein R.sub.3 is hydrogen, fluoro, chloro, bromo, nitro and --CF.sub.3 ; and wherein A is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl, and 2-pyridyl, are prepared by treating a hydrazino compound of the formula: ##STR2## with a carbonyl compound II: ##STR3## wherein R.sub.1 is defined as above, and R', R" are alkyl of 1 to 3 carbon atoms, inclusive or the group ##STR4## is a cyclic acetal to give a compound of formula III: ##STR5## wherein R.sub.1, R.sub.2, R.sub.3, R', R" and Ar are defined as above, and cyclizing compound III to give the compound IV above.Compounds III and IV, including the pharmacologically acceptable acid addition salt of these compounds, have sedative, anxiolytic and muscle-relaxing activity and can be used for the treatment of anxieties or muscle strains of mammals, including man.
    Type: Grant
    Filed: December 30, 1977
    Date of Patent: August 15, 1978
    Assignee: The Upjohn Company
    Inventor: Gerald N. Evenson
  • Patent number: 4098791
    Abstract: An improved multistep process for the production of intermediates for hypotensive compounds, which intermediates are of the formula V: ##STR1## wherein R.sub.1 and R.sub.2 are lower alkyl of 1 to 4 carbon atoms, inclusive, alkenyl of 3 or 4 carbon atoms, cycloalkyl from 3 to 7 carbon atoms, phenylalkyl in which the alkyl group is defined as above, or the group ##STR2## is a heterocyclic moiety of 4 to 8 ring members, e.g., azetidinyl, piperidino, pyrrolidinyl, hexahydroazepinyl, or heptamethyleneimino, each of which can be substituted by one or two methyl groups, N-alkylpiperazino, wherein alkyl is defined as above, morpholino, or thiomorpholino, and wherein R.sub.3 is hydrogen or alkyl of 1 to 4 carbon atoms, inclusive, starts with the corresponding secondary amine I ##STR3## wherein R.sub.1 and R.sub.2 have the significance of above.
    Type: Grant
    Filed: July 29, 1977
    Date of Patent: July 4, 1978
    Assignee: The Upjohn Company
    Inventors: Thomas A. Hylton, Muniraj D. Pillai
  • Patent number: 4086230
    Abstract: Compounds of the formula: ##STR1## wherein R.sub.1 is alkyl of 1 to 3 carbon atoms, inclusive; wherein R.sub.2 is hydrogen, methyl or ethyl; wherein R.sub.3 is hydrogen, fluoro, chloro, bromo, nitro and -CF.sub.3 ; and wherein Ar is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl, and 2-pyridyl, are prepared by treating a hydrazino compound of the formula: ##STR2## with a carbonyl compound II: ##STR3## wherein R.sub.1 is defined as above, and R', R" are alkyl of 1 to 3 carbon atoms, inclusive, or the group ##STR4## is a cyclic acetal, such as ##STR5## to give a compound of formula III: ##STR6## wherein R.sub.1, R.sub.2, R.sub.3, R', R" and Ar are defined as above, and cyclizing compound III to give the compound IV above.Compounds III and IV, including the pharmacologically acceptable acid addition salt of these compounds, have sedative, anxiolytic and muscle-relaxing activity and can be used for the treatment of anxieties or muscle strains of mammals, including man.
    Type: Grant
    Filed: March 9, 1977
    Date of Patent: April 25, 1978
    Assignee: The Upjohn Company
    Inventor: Gerald N. Evenson
  • Patent number: 4081452
    Abstract: Compounds of the formula: ##STR1## wherein R'.sub.o and R".sub.o are hydrogen or alkyl of 1 to 3 carbon atoms, inclusive; R.sub.1 is hydrogen, fluoro, chloro, bromo, nitro, trifluoromethyl, or alkylthio in which the alkyl moiety is of 1 to 3 carbon atoms, inclusive; R.sub.2 is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl and 2-pyridyl are prepared by multistep reactions from compounds of formula I: ##STR2## wherein R.sub.1 and R.sub.2 are defined as above and X is chlorine or bromine.Compounds of formula III, intermediates in the preparation thereof, Schiff's bases of compounds IIIA (III in which R'.sub.o and R".sub.o are hydrogen), and the pharmacologically acceptable acid addition salts are useful in birds and mammals, including man, as sedatives, antianxiety, antidepressant, anticonvulsive, and muscular relaxing agents.
    Type: Grant
    Filed: August 12, 1976
    Date of Patent: March 28, 1978
    Assignee: The Upjohn Company
    Inventor: Jackson B. Hester, Jr.
  • Patent number: 4075202
    Abstract: A s-triazolo-1,5-benzodiazepin-4-one selected from the group of compounds of the formulae: ##STR1## wherein R.sub.o is hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, hydroxy, hydroxymethyl, and ##STR2## in which R" and R'" are hydrogen or alkyl defined as above, or together ##STR3## is selected from the group consisting of pyrrolidino, piperidino, morpholino, and N-methylpiperazino; wherein R is hydrogen, alkyl of 1 to 3 carbon atoms, inclusive and ##STR4## in which R" and R'" are hydrogen or alkyl as defined above or together ##STR5## is defined as above; wherein R.sub.1 is hydrogen or methyl; wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are selected from the group consisting of hydrogen, alkyl alkyl defined as above, halogen, nitro, trifluoromethyl, and alkylthio in which alkyl is defined as above are produced from the corresponding 4-hydrazino-2H-1,5-benzodiazepines-2-ones of the formula (11A) ##STR6## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.
    Type: Grant
    Filed: September 27, 1973
    Date of Patent: February 21, 1978
    Assignee: The Upjohn Company
    Inventor: Robert Bruce Moffett
  • Patent number: 4075221
    Abstract: An improved process for the production of 1-dialkyl-amino-ethyl-6-aryl-4H-s-triazolo[4,3-a][1,4]benzodiazepines of the formula II: ##STR1## wherein R.sub.1 is alkyl of 1 to 3 carbon atoms, inclusive; wherein R.sub.2 is hydrogen, methyl or phenyl; wherein the ring A is unsubstituted, or monosubstituted with fluoro, chloro, bromo, nitro, trifluoromethyl or methylthio; and wherein Ar is phenyl; o-chlorophenyl; o-fluorophenyl; 2,6-difluorophenyl or 2-pyridyl, is carried out by reacting a compound of the Formula I: ##STR2## wherein ring A, Ar and R.sub.2 are defined as above, with a dialkylmethyleneammonium salt in the presence of a reactive carboxylic acylating agent.The compounds of Formula II (R.sub.2 .dbd.H) are known compounds (Belgian Pat. No. 782,84g) which have sedative-tranquilizing as well as pronounced anti-depressant activity, suitable for the treatment of anxieties and depressions in mammals, including man.
    Type: Grant
    Filed: January 24, 1977
    Date of Patent: February 21, 1978
    Assignee: The Upjohn Company
    Inventor: Jackson B. Hester, Jr.
  • Patent number: 4073785
    Abstract: Compounds of the formula IV ##STR1## wherein R is hydrogen or alkyl of 1 or 2 carbon atoms; wherein R.sub.1 is alkyl of 1 to 3 carbon atoms, inclusive; or ##STR2## is a 2-cycloalkenylene ring of 5 or 6 carbon atoms; wherein R.sub.2 is hydrogen, methyl or ethyl; wherein R.sub.3 is hydrogen, fluoro, chloro, bromo, nitro and --CF.sub.3 ; and wherein Ar is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl, and 2-pyridyl, are prepared by treating a hydrazino compound of the formula: ##STR3## wherein Ar and R.sub.3 are defined as above, with a dicarbonyl compound II: ##STR4## and cyclizing the resulting compound III to give the compound IV above. Compound IV, including the pharmacologically acceptable acid addition salt of these compounds, have sedative, anxiolytic and muscle-relaxing activity and can be used for the treatment of anxieties or muscle strains of mammals, including man.
    Type: Grant
    Filed: March 9, 1977
    Date of Patent: February 14, 1978
    Assignee: The Upjohn Company
    Inventors: Gerald N. Evenson, Robert B. Moffett
  • Patent number: 4073784
    Abstract: Compounds of the formula V ##STR1## wherein R.sub.1 is hydrogen, alkyl of 1 to 3 carbon atoms, inclusive; ##STR2## in which n is 2 or 3; and X is hydrogen, fluoro or chloro; wherein R.sub.2 is hydrogen, methyl or ethyl; wherein R.sub.3 is hydrogen, fluoro, chloro, bromo, trifluoromethyl and nitro; and wherein Ar is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl or 2-pyridyl are prepared by treating a hydrazino compound of the formula: ##STR3## WHEREIN Ar, R.sub.2 and R.sub.3 are defined as above with an alkyl oxalyl chloride and cyclizing the obtained products. Compound V, including the pharmacologically acceptable acid addition salt thereof, have sedative, anxiolytic and muscle-relaxing activity and can be used for the treatment of anxieties or muscle strains of mammals, including man.
    Type: Grant
    Filed: March 9, 1977
    Date of Patent: February 14, 1978
    Assignee: The Upjohn Company
    Inventor: Robert B. Moffett
  • Patent number: 4049699
    Abstract: Ibuprofen p-hydroxybenzaldehyde semicarbazone ester having the formula II: ##STR1## was prepared from the free acid, ibuprofen [.+-.2-(p-isobutylphenyl)propionic acid] (I).The ester II above has the anti-inflammatory activity of the free acid, but in contradistinction to it, it has a pleasant taste, suitable for oral administration such as uncoated tablets, suspensions or syrups, for the treatment of inflammatory conditions, particularly arthritis.
    Type: Grant
    Filed: June 17, 1976
    Date of Patent: September 20, 1977
    Assignee: The Upjohn Company
    Inventor: Anthony A. Sinkula
  • Patent number: 4049700
    Abstract: Ibuprofen p-hydroxyphenylurea ester having the formula II: ##STR1## was prepared from the free acid, ibuprofen [.+-.2-(p-isobutylphenyl)propionic acid](I).The ester II above has the anti-inflammatory activity of the free acid, but in contradistinction to it, it has a pleasant taste, suitable for oral administration such as uncoated tablets, suspensions or syrups, for the treatment of inflammatory conditions, particularly arthritis.
    Type: Grant
    Filed: June 17, 1976
    Date of Patent: September 20, 1977
    Assignee: The Upjohn Company
    Inventor: Anthony A. Sinkula
  • Patent number: 4039551
    Abstract: Compounds of the formula ##STR1## wherein R.sub.o is hydrogen or alkyl of 1-3 carbon atoms, inclusive; wherein R.sub.1 is hydrogen, fluoro, chloro, bromo, nitro, trifluoromethyl or alkylthio in which the alkyl moiety is of 1 to 3 carbon atoms, inclusive; and wherein R.sub.2 is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl or 2-pyridyl, or the pharmaceutically acceptable acid addition salts thereof. The compounds are useful as sedatives, antianxiety agents, antidepressants, anticonvulsives and muscle-relaxing agents.
    Type: Grant
    Filed: August 12, 1976
    Date of Patent: August 2, 1977
    Assignee: The Upjohn Company
    Inventor: Jackson B. Hester, Jr.