Patents Represented by Attorney John T. Reynolds
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Patent number: 4576399Abstract: A three panel format and method useful to (a) office, (b) clinical research and (c) statistical personnel in connection with the preparation, identification and statistical evaluation of controlled, blinded code designated samples are provided. The format comprises a write-on panel (A) for mounting code designations, and test substance identities arranged so that the code designations will be transferred through panel (A), and a second, removable panel (B) having rows of writing transference substance thereon to a third panel (C), without transferring the test substance to said panel (C), when panel (A) is folded into an in-line writing relationship with said panels (B) and (C). Thereafter, panels (A) and (C) are folded 360.degree. and sealed in an in-line relationship for use thereafter by clinical and statistical personnel.Type: GrantFiled: November 7, 1983Date of Patent: March 18, 1986Assignee: The Upjohn CompanyInventors: Cathleen A. White, Richard K. Senne, Harry Rutherford
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Patent number: 4560767Abstract: Amino-cycloalkenyl-amide compounds, e.g., (1.alpha.,6.beta.)-(.+-.)-3,4-dichloro-N-methyl-N-(6-(1-pyrrolidinyl)-3-cy clohexen-1-yl)benzeneacetamide, and tritiated derivatives thereof, are useful as analgesics and as radio labeled compounds for pharmacological and metabolism studies in animals.Type: GrantFiled: June 17, 1983Date of Patent: December 24, 1985Assignee: The Upjohn CompanyInventors: John M. McCall, Robert A. Lahti
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Patent number: 4547499Abstract: 2,4-Dihydro-2-(omega-aminoalkyl)-1H-[1,2,4]triazolo[3,4-c][1,4]benzoxazin-1 -ones of the formula ##STR1## where n and -NRR are as defined in the specification, e.g., 2-[4-[4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)piperadinyl]butyl]-2,4-dih ydro-1H-[1,2,4]triazolo[3,4-c][1,4]benzoxazin-1-one, are disclosed. They are useful for treating hypertension or allergy conditions in humans and valuable animals.Type: GrantFiled: May 10, 1984Date of Patent: October 15, 1985Assignee: The Upjohn CompanyInventor: Jackson B. Hester, Jr.
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Patent number: 4540690Abstract: 2-(Phenylmethylene)cycloalkylamines and -azetidines of the formula ##STR1## and acid addition salts thereof, e.g., 1-[2-(phenylmethylene)cyclohexyl]azetidine, and related compounds, which have analgesic, antidepressant and mixed analgesic/antidepressant central nervous system (CNS) activities, and which are useful in treating pain and/or depression in mammals including humans. The invention provides processes for preparing the compounds as well as compositions containing the compounds and methods for using the compounds as analgesic and/or antidepressant drugs for humans and valuable mammalian animals.Type: GrantFiled: August 16, 1982Date of Patent: September 10, 1985Assignee: The Upjohn CompanyInventor: Jacob Szmuszkovicz
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Patent number: 4514407Abstract: Triazolo-benzodiazepine-1-ethanamines of the formulas ##STR1## where R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and Ring A are as defined in the specification, e.g., 8-chloro-N,N-dimethyl-.beta.,6-diphenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benz odiazepine-1-ethanamine, and pharmacologically acceptable salts thereof, have been found to have substantial diuretic, natriuretic, but little, if any, kaliuretic activity, which can be used alone, or concomittently with other diuretic drugs such as furosemide or hydrochlorothiazide and/or with antihypertensive agents such as propranolo, captopril, minoxidil, prazosin, guanadrel sulfate, whose actions are supplemented by the action of a diuretic drug.Type: GrantFiled: March 17, 1983Date of Patent: April 30, 1985Assignee: The Upjohn CompanyInventors: Jackson B. Hester, Jr., James H. Ludens
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Patent number: 4508911Abstract: 1,2-Cycloaliphatic diamines and protected diamines of the formulas II and IIa ##STR1## and ##STR2## wherein the wavy line bonds, p, n, R, R.sub.1, R.sub.2, Z, m and Q are as defined in the specification, e.g., (.+-.)-(5.xi.,6.alpha.,7.beta.)-1-[6-methylamino-1-oxaspiro[4.5]dec-7-yl]p yrrolidine, are disclosed and claimed herein. These diamines and protected diamines are useful as intermediates for preparing mono-oxa, and thiaspirocyclic-benzene acetamide and benzamide analgesic compounds.Type: GrantFiled: February 14, 1984Date of Patent: April 2, 1985Assignee: The Upjohn CompanyInventor: Lester J. Kaplan
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Patent number: 4501698Abstract: A process is provided for converting 1-hydrogen-triazolo[4,3-a]-[1,4]benzodiazepines, e.g., estazolam, to 1-(hydroxymethyl)-triazolo-[4,3-a][1,4]benzodiazepines, and, if desired, these 1-(hydroxymethyl)-compounds to 1-aminomethyl compounds, e.g., to adinazolam, without the need for column chromatography or sealed tube procedures, and while minimizing 1,4-bis-(hydroxymethyl)- group formation.Type: GrantFiled: March 31, 1983Date of Patent: February 26, 1985Assignee: The Upjohn CompanyInventor: John R. Palmer
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Patent number: 4476248Abstract: Ibuprofen is crystallized from a .delta.H.gtoreq.8 liquid such as a C.sub.1 to C.sub.3 -alkanol, e.g., methanol, containing solutions thereof to obtain ibuprofen crystals which are equant (cube, sphere or grain) in shape, which ibuprofen crystals have larger average partile size, higher bulk density, lower bulk volume and improved flow properties compared to previously known bulk ibuprofen crystalline materials.Type: GrantFiled: July 25, 1983Date of Patent: October 9, 1984Assignee: The Upjohn CompanyInventors: Roger E. Gordon, Sanjay I. Amin
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Patent number: 4474699Abstract: An improved process for preparing a 1-aminomethyl-6-substituted-4H-s-triazolo[4,3-a][1,4]benzodiazepine product, e.g., adinazolam, directly from the corresponding 1-hydrogen-6-substituted-4H-s-triazolo[4,3-a][1,4]benzodiazepine starting material, e.g., from estazolam, by conducting the reaction between the estazolam-type compound and the dimethylaminomethylene salt in the selected solvent in the presence of an alkali metal carbonate, and thereafter extracting the 1-aminomethyl-6-substituted-4H-s-triazolo[4,3-a]-[1,4]benzodiazepine from an aqueous organic solvent mixture thereof into a halogenated C.sub.1 to C.sub.3 -alkane solvent while maintaining the pH of the aqueous phase between pH 3.0 and 4.0, and thereafter recovering the product from the halogenated alkane solvent.Type: GrantFiled: May 25, 1983Date of Patent: October 2, 1984Assignee: The Upjohn CompanyInventors: Donald J. Cram, Martin Gall, Michael F. Lipton
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Patent number: 4472397Abstract: Certain 1-(Nitrogen-containing group)-triazolo-benzodiazepines, e.g., adinazolam, are useful for treating psychotic, including schizophrenic, conditions in human patients.Type: GrantFiled: February 18, 1983Date of Patent: September 18, 1984Assignee: The Upjohn CompanyInventors: Robert Lahti, Robert E. Pyke
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Patent number: 4466977Abstract: Cis- and trans-N-[2-amino(oxy- or thia group-substituted-cycloaliphatic)]benzeneacetamide and -benzamide compounds, e.g., 3,4-dichloro-N-[4,4-dimethoxy-2-(1-pyrrolidinyl)cyclohexyl]-N-methylbenzen eacetamide, and salts thereof, are provided. These compounds have analgesic properties. Processes for their preparation are disclosed. Pharmaceutical compositions and methods of use are also provided.Type: GrantFiled: November 4, 1982Date of Patent: August 21, 1984Assignee: The Upjohn CompanyInventors: Moses W. McMillan, Jacob Szmuszkovicz
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Patent number: 4463013Abstract: Conditions of inappropriate hyperhydration in warm blooded animals can be treated with an essentially water only diuretic drug compound selected from the group ##STR1## wherein m, n, p, A, E, R, R.sub.1, R.sub.2, X, Y and Z are as defined in the specification, e.g., trans-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)-1,4-dioxaspiro[4.5]dec-8 -yl]benzeneacetamide, or a pharmaceutically acceptable salt thereof, ##STR2## wherein R, R.sub.1, R.sub.2, R.sub.3, P, Q, X and Y are as defined in the specification, e.g., 3,4-dichloro-N-[[8-(1-pyrrolidinyl)-1,4-dioxaspiro[4.5]-dec-8-yl]methyl]be nzeneacetamide, or a pharmaceutically acceptable salt thereof, or ##STR3## where R, R.sup.1, R.sup.2, X and Y are as defined in the specification, e.g., trans-(1)-2-(3,4-dichlorophenyl)-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] acetamide,or ##STR4## wherein p, n, q, X, Y, R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, E, R.sub.5, R.sub.6 are as defined in the specification,or ##STR5## wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.Type: GrantFiled: August 18, 1982Date of Patent: July 31, 1984Assignee: The Upjohn CompanyInventors: Robert J. Collins, Lester J. Kaplan, James H. Ludens, Philip F. Von Voigtlander
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Patent number: 4460600Abstract: Cis- and trans-N-[2-amino(adjacenty substituted bis(alkyloxy), bis(alkylthio), alkylthio or mercapto group substituted)-cycloaliphatic]benzeneacetamide and -benzamide compounds, e.g., (.+-.)-(1.alpha.,2.beta.)-4-bromo-N-[3,3-dimethoxy-2-(1-pyrrolidinyl)cyclo hexyl]-N-methylbenzamide, and salts thereof, are provided. These compounds have analgesic properties. Processes for their preparation are disclosed. Pharmaceutical compositions and methods of use are also provided.Type: GrantFiled: November 4, 1982Date of Patent: July 17, 1984Assignee: The Upjohn CompanyInventors: Lester J. Kaplan, Moses W. McMillan, Jacob Szmuszkovicz
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Patent number: 4438130Abstract: Mono-Oxa-, thiaspirocyclic-benzene-acetamide and -benzamide compounds of the formula ##STR1## wherein p, n, m, A, E, R, R.sub.1, R.sub.2, X, Y and Z are as defined in the specification, e.g., (.+-.)-(5.alpha.,7.alpha.,9.beta.)-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidi nyl)-1-oxaspiro[4.5]dec-8-yl]benzeneacetamide, and the pharmacologically acceptable salts thereof, are useful as analgesic compounds having low physical dependence liability, compared to morphine and methodone, and low dysphoria side effects. Some of these compounds have potent analgesic activity when administered orally, and some have low CNS sedative side effects. Pharmaceutical compositions and methods for using these compounds as analgesics are disclosed. Processes for preparing this class of compounds are also disclosed.Type: GrantFiled: June 21, 1982Date of Patent: March 20, 1984Assignee: The Upjohn CompanyInventor: Lester J. Kaplan
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Patent number: 4361580Abstract: Aluminum ibuprofen pharmaceutical liquid suspensions having improved resistance to dissolution rate reduction upon storage containing aluminum ibuprofen, a suspending agent have a particle size below 50 microns, a water-soluble surface active agent, water, and preferably also from 5 to 30 grams of sucrose per 100 ml of suspension are disclosed, or its sweetening equivalent of glucose, fructose, sodium saccharin sodium cyclamate, or mixtures thereof.Type: GrantFiled: May 11, 1981Date of Patent: November 30, 1982Assignee: The Upjohn Manufacturing CompanyInventors: Susanne M. Peck, Lois J. Larion, Englebert L. Rowe
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Patent number: 4360531Abstract: [2-Amino(substituted cycloaliphatic)]benzeneacetamide and benzamide compounds, e.g., trans-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)-1,4-dioxaspiro[4.5]dec-8 -yl]benzeneacetamide, have useful analgesic activity and low abuse or physical dependence liability, or are useful as chemical intermediates for producing such analgesic compounds. Processes for their preparation are disclosed. Pharmaceutical compositions and methods of use are also disclosed.Type: GrantFiled: April 9, 1981Date of Patent: November 23, 1982Assignee: The Upjohn CompanyInventors: Moses W. McMillan, Jacob Szmuszkovicz
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Patent number: 4359476Abstract: N-[2-Amino(oxy or thio group) substituted-cycloaliphatic]phenylacetamide and -benzamide compounds, having the oxy- or thio group substituents on a cycloaliphatic ring carbon adjacent to either of the nitrogen bearing carbons of the cycloaliphatic ring, e.g., cis- and trans-4-bromo-N-[3-methoxy-2-(1-pyrrolidinyl)cyclohexyl]-N-methylbenzamide , and trans-3,4-dichloro-N-methyl-N-[7-(1-pyrridolinyl)-1,4-dioxaspiro[4.5]dec-6 -yl]benzeneacetamide, and salts thereof, have useful analgesic activity and low abuse liability in humans and valuable warm blooded animals. Processes for their production and pharmaceutical compositions and method of use are also disclosed.Type: GrantFiled: April 9, 1981Date of Patent: November 16, 1982Assignee: The Upjohn CompanyInventors: Lester J. Kaplan, Moses W. McMillan, Jacob Szmuszkovicz
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Patent number: 4346101Abstract: Benzamide derivative analgesic compounds of the formula ##STR1## wherein P, Q, R.sub.1, R.sub.2, X and Y are as defined in the specification, e.g., 3,4-Dichloro-N-[[8-(dimethylamino)-1,4-dioxaspiro[4.5]dec-8-yl]methyl]benz amide, and their pharmacologically acceptable salts, have analgesic drug properties with a low ratio of analgesic to sedative activity for use as analgesic drugs in mammalian animals, including humans.Type: GrantFiled: December 8, 1980Date of Patent: August 24, 1982Assignee: The Upjohn CompanyInventor: Daniel Lednicer
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Patent number: 4338459Abstract: A diester of .alpha.-acetyl-.alpha.'-methylsuccinic acid is prepared in improved yield under substantially anhydrous process conditions which minimizes decomposition of that diester by reacting an acetoacetate ester with an .alpha.-halopropionate ester in a solvent mixture containing a non-polar, aprotic liquid, e.g., toluene, and a dipolar aprotic liquid, e.g., DMF, at from about 50.degree. C. to reflux temperature in the presence of a phase transfer agent, a catalytic amount of iodide ion and solid form, substantially anhydrous alkali metal base or basic salt. Further improvement is obtained when the completed reaction mixture is diluted with water and adjusted to pH 8 to 9, and when the DMF/acetoacetate ester ratios are between about 1.7 and 3. The resulting diesters can be used under the conditions of this invention as intermediates in processes for making ibuprofen by combining and reacting the .alpha.-acetyl-.alpha.Type: GrantFiled: March 5, 1981Date of Patent: July 6, 1982Assignee: The Upjohn CompanyInventor: Francis L. Shenton
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Patent number: RE30837Abstract: N-(2-aminocycloheptyl)N-alkanoylanilides and their 2-N-oxides of the formula ##STR1## e.g., trans-3,4-dichloro-N-[2-(allylamino)cycloheptyl]propionanilide, and their pharmacologically acceptable salts, have been found to possess potent Central Nervous System antidepressant properties. Many of them are new.These compounds are promising antidepressant drugs which are characterized by lower toxicity than imipramine, and long acting activity which may allow longer durations between administrations, e.g., once a day. Pharmaceutical compositions containing these compounds and a process for treating conditions of depression with these compositions are disclosed.Type: GrantFiled: September 24, 1980Date of Patent: December 29, 1981Assignee: The Upjohn CompanyInventor: Jacob Szmuszkovicz