Abstract: Non-disintegrating theophylline tablets having a pair of opposing substantially planar surfaces and a very thin cross-section have a high bioavailability on ingestion and a relatively steady release rate permitting a 12 hr. dosing interval for maintenance of non-toxic therapeutic blood theophylline concentrations. Excipients or tableting aids are not required, but trace amounts of a tableting lubricant are preferably included to facilitate continuous large scale production.
Type:
Grant
Filed:
December 21, 1982
Date of Patent:
August 14, 1984
Assignee:
Mead Johnson & Company
Inventors:
Stephen T. David, Dana Brooke, Claude E. Gallian
Abstract: A process for resolving a racemic modification of .beta.-adrenergic aryl- or hetaryl-oxypropanolamines such as (.+-.)-2-[2-hydroxy-3-[[2-(1H-indol-3-yl)-1,1-dimethylethyl]amino]propoxy] benzonitrile into its individual enantiomers is described. The process comprises converting the racemic modification into a pair of diastereomeric urea derivatives by reaction with a chiral aralkylisocyanate; separation into the individual diastereomers; and facile regeneration of the starting amine by cleavage of the intermediate urea compound using hydrazine. This final step is improved by the addition of an .alpha.-keto carboxylic acid, such as pyruvic acid, which functions as a scavenger of nucleophilic by-products.
Type:
Grant
Filed:
September 13, 1982
Date of Patent:
July 31, 1984
Assignee:
Mead Johnson & Company
Inventors:
Ronald D. Dennis, Terence M. Dolak, William E. Kreighbaum
Abstract: Piperazinyl derivatives containing a spiro-2,4-thiazolidinedione heterocyclic component with relatively selective psychotropic properties are disclosed. The compound 2-[4-[4-(7,9-dioxo-6-thia-8-azaspiro[4.4]nonan-8-yl)butyl]-1-piperazinyl]p yridine-3-carbonitrile which has selective anti-psychotic activity constitutes a typical embodiment of the invention.
Type:
Grant
Filed:
August 3, 1981
Date of Patent:
June 26, 1984
Assignee:
Mead Johnson & Company
Inventors:
Davis L. Temple, Jr., Richard E. Yeager
Abstract: An improved process for the preparation of 4-methoxy-2'-{2-(1-methyl-2-piperidyl)ethyl}benzanilide has been developed. The process comprises essentially three steps starting with methyl anthranilate and 2-picoline and features a novel low-pressure hydrogenation sequence.
Abstract: Disubstituted N,N-piperazinyl derivatives are disclosed wherein one substituent is benzisothiazol-3-yl or benzisoxazol-3-yl and the other is alkylene attached to heterocycles such as azaspiro[4.5]decanedione, dialkylglutarimide, thiazolidinedione and spirocyclopentylthiazolidinedione or butyrophenone-like groups. The compounds have psychotropic properties and 8-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]-8-azaspiro[4.5]deca ne-7,9-dione is a typical embodiment having selective antipsychotic activity.
Abstract: Buspirone and its pharmaceutically acceptable salts are useful in alleviation of extrapyramidal motor disorders which can take the form of clinical syndromes such as Parkinsonism and neuroleptic-induced extrapyramidal symptoms (EPS).
Abstract: Loss of potency of estradiol cream compositions found to be due to unexpected oxidation of estradiol. Improved cream composition comprises 1% or less 17.beta.-estradiol in the presence of stabilizing members selected from phenolic-type antioxidants, metal chelating agents, and suspending agents.
Type:
Grant
Filed:
March 15, 1982
Date of Patent:
March 13, 1984
Assignee:
Mead Johnson & Company
Inventors:
Robert J. Bequette, Linda G. Hobbs, Joseph A. Scott
Abstract: 1-[4-(4,4-Dialkyl-2,6-piperidinedion-1-yl)butyl]piperazines with 2-pyrimidyl substituents in the 4- position have been synthesized and demonstrate useful anxiolytic properties. The compound 4,4-dimethyl-1-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,6-piperidinedi one, which has selective anxiolytic activity, constitutes the preferred embodiment of the invention.
Abstract: This invention concerns an isethionic acid addition salt of the non-adrenergic bronchodilating agent 9-cyclohexyl-2-propoxy-9H-purine-6-amine. The salt is comprised of a 2:1 molecular ratio of the isethionic acid to the adenine base. The salt of the invention is characterized in having improved water solubility and stability.
Abstract: Novel spiro-quaternary ammonium halides are disclosed. The new compounds are particularly valuable as intermediates in preparation of N-(2-pyrimidinyl)piperazinylalkyl derivatives of azaspiroalkanediones such as the psychopharmacologic agent 8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dio ne.
Abstract: A series of 1,4-dihydropyrid-5-yl cyclic imidate esters have been prepared possessing the general formula ##STR1## wherein R and R.sup.1 are independently selected from hydrogen, lower alkyl or alkoxyalkyl groups; R.sup.2 is lower alkyl, aryl, or hetaryl; R.sup.3 is cycloalkyl, aryl or hetaryl, generally with electron-withdrawing substituents; R.sup.4 is lower alkyl, alkoxyalkyl, aminoalkyl, haloalkyl, or dialkylaminoalkyl; R.sup.5 is lower alkyl or aryl; m is 0 or 1; and n is 0, 1, or 2. Compounds of this series demonstrate blockage of calcium ion flux in tissue preparations in vitro and vasodilation in animal testing in vivo.
Type:
Grant
Filed:
March 22, 1982
Date of Patent:
November 8, 1983
Assignee:
Mead Johnson & Company
Inventors:
Graham S. Poindexter, David L. Temple, Jr.
Abstract: Disubstituted N,N-piperazinyl derivatives are disclosed wherein one substituent is benzisothiazol-3-yl or benzisoxazol-3-yl and the other is alkylene attached to heterocycles such as azaspiro[4.5]decanedione, dialkylglutarimide, thiazolidinedione and spirocyclopentylthiazolidinedione or butyrophenone-like groups. The compounds have psychotropic properties and 8-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]-8-azaspior[4.5]deca ne-7,9-dione is a typical embodiment having selective antipsychotic activity.
Abstract: Imidazopyrimidinones and other diazaheterocyclopyrimidinones having an additional fused imidazole or triazole ring have utility as bronchodilators, mediator release inhibitors, phosphodiesterase inhibitors, and peripheral vasodilators. They are orally active and useful in the prophylaxis and treatment of asthma. A preferred compound is 4-[(4-chlorophenyl)methyl]-6,7-dihydro-3H-imidazo[1,2-a]-purin-9(4H)-one.
Abstract: 2-Phenethylpiperidines bearing urea, thiourea, and amidine substituents in the ortho-position of the phenethyl moiety have been synthesized and demonstrate useful antiarrhythmic properties. These novel compounds are prepared by reaction of appropriately substituted o-amino-phenethylpiperidines with appropriately substituted phenyl isothiocyanates, phenyl isocyanates, or phenyl imino esters.
Abstract: An improved process for the preparation of 4-methoxy-2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide has been developed. The process comprises essentially three steps starting with methyl anthranilate and 2-picoline and features a novel low-pressure hydrogenation sequence.
Abstract: Phenoxyalkyl substituted-1,2,4-triazolones having antidepressant properties typified by 4-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-ethyl-2,4-dihydro-2-(2-ph enoxyethyl)-3H-1,2,4-triazol-3-one are disclosed.
Type:
Grant
Filed:
February 24, 1982
Date of Patent:
May 31, 1983
Assignee:
Mead Johnson & Company
Inventors:
Davis L. Temple, Jr., Walter G. Lobeck, Jr.
Abstract: Treatment of the antiallergic agent 3,4-dihydro-5-methyl-6-(2-methylpropyl)-4-oxothieno[2,3-d]pyrimidine-2-car boxylic acid with N-methyl-D-glucamine gives a salt with improved solubility. Solutions of this salt have pH values in a range acceptable for topical formulations. Additionally, solutions of the subject salt exhibit good stability which can be demonstrated by retention of potency. The salt is comprised of a 1:1 molecular ratio of the glucamine base to the acid.
Abstract: N-Phenyl amidines which have diuretic, antithrombogenic, smooth muscle relaxant, anti-inflammatory and antiarrhythmic properties have been discovered. They are prepared by reacting a substituted aniline with a carboxamide selected from the group consisting of amides and lactams in the presence of phosphorus oxychloride. Typical examples of substituted N-phenyl amidines thus obtained are 5-methyl-2-(N-phenylbenzylamino)-1-pyrroline, 2-(N-phenylbenzylamino)-1-pyrroline, 3-[(N-1-pyrrolin-1-yl-p-anisidino)methyl]indole and 4,5,6,7,8,9-hexahydro-2-(N-phenylphenethylamino)-3H-azonine. Indole substituted N-phenyl amidines can be rearranged to provide iminopyrrolinidinylindoles which are useful as diuretic, antithrombogenic and smooth muscle relaxant agents. In the case of 3-[(N-1-pyrrolin-2-yl-p-anisidino)methyl]indole, the rearranged product is 3-[[2-p-methoxyphenylimino)-1-pyrrolidinyl]methyl]indole.