Abstract: Compounds having the formula: ##STR1## which are ester prodrugs of potent dopamine-.beta.-hydroxylase inhibitors and thus are useful to inhibit dopamine-.beta.-hydroxylase activity, pharmeceutical compositions including these compounds, and methods of using these compounds to inhibit dopamine-.beta.-hydroxylase activity in mammals.
Type:
Grant
Filed:
April 8, 1986
Date of Patent:
May 10, 1988
Assignee:
SmithKline Beckman Corporation
Inventors:
James S. Frazee, Carl Kaiser, Lawrence I. Kruse, Stephen T. Ross
Abstract: Peptides whose structures resemble those of vasopressin antagonists but have both a carboxamido amino acid unit and a basic amino acid unit in the side chain have good antagonist activity. A species of the invention is [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid)-2-(O-ethyl)-D-tyrosine-4-valine-8-glutamine-9-desglycine]-vasopressi n.
Type:
Grant
Filed:
October 23, 1985
Date of Patent:
May 3, 1988
Assignee:
Smithkline Beckman Corporation
Inventors:
William M. Bryan, William F. Huffman, Michael L. Moore
Abstract: The compounds represented by the following structural formula (I) ##STR1## wherein m is 1 or 2; n is 1, 2 or 3; R' is hydrogen or methyl; R is a radical selected from the group consisting of: ##STR2## wherein R.sub.1 is C.sub.8 to C.sub.13 alkyl, C.sub.7 to C.sub.12 alkoxy, C.sub.7 to C.sub.12 thioalkyl, C.sub.10 to C.sub.12 1-alkynyl, 11-dodecynyl, 1-trans-dodecenyl, 5-(4-acetyl-3-hydroxy-2-propylphenoxypentoxy, 2(Z), 5(Z)-undecadienyloxy, phenyl-C.sub.4 to C.sub.10 alkyl with the phenyl optionally mono substituted with bromo, chloro, trifluoromethyl, methoxy, methylthio or trifluoromethylthio, phenylthio-C.sub.3 to C.sub.9 alkyl with the phenyl optionally mono substituted with bromo, chloro, trifluoromethyl, methoxy, methylthio or trifluoromethylthio, phenyl-CH.dbd.CH--(CH.sub.2).sub.2-8, phenyl-C.sub.3 to C.sub.9 alkoxy, trifluoromethyl-C.sub.7 to C.sub.12 alkyl, cyclohexyl- C.sub.4 to C.sub.10 alkyl or ##STR3## wherein each q is 0, 1, 2 or 3 but the sum of both q's does not exceed 3, and R.sub.
Abstract: Novel compounds, pharmaceutical compositions and a method of inhibiting the 5-lipoxygenase products in an animal in need thereof which comprises administering an effective, 5-lipoxygenase pathway inhibiting amount of a 2,2'-[1,2-ethanediylbis-(thio)]-bis-1H-imidazole or 2,2'-[(1,3-propan-2-onediylbis-(thio)]bis-1H-imidazole, or a pharmaceutically acceptable salt thereof, to such animal.
Abstract: 1-substituted-2-mercapto(or aminomethyl)benzimidazole compounds of the formula ##STR1## inhibit dopamine-.beta.-hydroxylase activity. Intermediates are also disclosed.
Abstract: A tamper evident seal for containers having a plastic shrink sleeve placed around the cap and neck and extending over the shoulder. A paper label is placed over a portion of the sleeve to prevent the sleeve from being removed intact. The sleeve has zigzag, saw-tooth perforations above and below a median line. The perforations are between the shoulder and cap of the container. When the cap is twisted and removed the plastic sleeve is randomly fragmented making it difficult, if not impossible to match in any attempt to reseal the container.
Abstract: Vasopressin antagonists which have a tripeptide side chain comprised of three basic amino acids, such as arginine, lysine or ornithine, demonstrate potent V.sub.1 and V.sub.2 -antagonist activity. A species of the invention, which is prepared by conventional peptide sequencing, is [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid)-2-(O-ethyl)-D-tyrosine-4-valine-7-arginine-8-arginine-9-arginine]-va sopression.
Abstract: Potent dopamine-.beta.-hydroxylase inhibitors having the Formula: ##STR1## which are useful to inhibit dopamine-.beta.-hydroxylase activity, pharmaceutical compositions including these inhibitors, and methods of using these inhibitors to inhibit dopamine-.beta.-hydroxylase activity in mammals. Also disclosed are novel intermediates useful in preparing the presently invented inhibitors.
Type:
Grant
Filed:
October 31, 1985
Date of Patent:
January 12, 1988
Assignee:
SmithKline Beckman Corporation
Inventors:
Carl Kaiser, Lawrence I. Kruse, Stephen T. Ross
Abstract: A method of inhibiting the production of 5-lipoxygenase products in an animal in need thereof which comprises administering an effective, 5-lipoxygenase pathway inhibiting amount of a 2(3)-(pyridyl)-3-(2)-substituted phenyl)-6,7-dihydro-[5H]-pyrrolo-[1,2-a]imidazole, a 2(3)-(pyridyl)-3(2)-(substituted phenyl)-5,6,7,8-tetrahydro-imidazo[1,2,-a]pyridine, or a pharmaceutically acceptable salt thereof, to such animal.
Abstract: 2- or 3-.beta.-Indolylalanyl and .beta.-indolylglycyl vasopressins are prepared by standard peptide synthetic methods. These 2- or 3-TRP vasopressins have vasopressin antagonist activity.
Abstract: Vasopressin antagonists which have a dipeptide side chain comprised of two basic amino acids demonstrate potent V.sub.1 and V.sub.2 -antagonist activity. A species of the invention, which is prepared by conventional peptide sequencing, is [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylene propionic acid)-2-(O-ethyl)-D-tyrosine-4-valine-7-arginine-8-arginine-9-desglycine]- vasopressin.
Abstract: A DNA fragment from Streptomyces sp. which contains a gene which can code for an excretable protein is isolated, inserted into a plamid vector and used to transform other Streptomycetes.
Type:
Grant
Filed:
December 14, 1984
Date of Patent:
January 5, 1988
Assignee:
SmithKline Beckman Corporation
Inventors:
Mary E. Brawner, Thomas G. Eckhardt, Louis R. Fare
Abstract: Heterocyclic phosphine compounds, pharmaceutical compositions containing an effective, tumor cell growth-inhibiting amount of such a compound, and a method for treating tumor cells sensitive to such a compound which comprises administering a tumor cell growth-inhibiting amount of such a compound to an animal afflicted by said tumor cells.
Abstract: Vasopressin derivatives having unexpected VSP site binding activity whose structures are characterized by a Mpr unit at position 1 and a Pen unit at position 6 are prepared by standard peptide synthetic methods also using an oxidative cyclization of a linear peptide dimercaptan. A representative species is [1-.beta.-mercaptopropionic acid-2-(O-ethyl)-D-tyrosine-4-valine-6-penicillamine-8-arginine]vasopressi n.
Abstract: Cysteamine is used as an active ingredient in animal feed compositions and in methods for increasing the feed efficiency of immature, monogastric, meat-producing animals. A particularly useful active ingredient of this invention is cysteamine hydrochloride in a quantity selected from the range of 15-1200 ppm.
Abstract: Compounds having the formula ##STR1## are .beta.-adrenergic receptor antagonists. Also disclosed are pharmaceutical compositions and methods for producing .beta.-adrenergic receptor antagonistic activity in animals including man.
Abstract: 1-Phenyl-3-benzazepine compounds are useful in treating gastrointestinal motility disorders. A particular compound of this invention is 8-hydroxy-3-methyl-1-phenyl-7-phenylthio-2,3,4,5-tetrahydro-1H-3-benzazepi ne.
Type:
Grant
Filed:
December 20, 1985
Date of Patent:
November 17, 1987
Assignee:
Smithkline Beckman Corporation
Inventors:
William E. Bondinell, Thomas Wen-Fu Ku, Herbert S. Ormsbee, III
Abstract: A polyene antibiotic emulsion formulation comprising a therapeutically effective amount of the antibiotic incorporated into an oil-in-water emulsion, and a method of treating an active infection in an animal caused by a microorganism with sterols in its cell membrane by parenterally administering the emulsion formulation to such animal.