Abstract: Novel polymers having a linear backbone which is free from both branching and cross-linking, comprising quaternized nitrogen atoms linked to each other through trimethylene groups. By the term "linear backbone" is meant that the polymer has only acyclic groups, i.e. trimethylene, linking the nitrogen atoms in a single continuous chain; the polymer is free from "branching" when it has no repeating monomer units extending from the polymer backbone; and it is free from "cross-linking" when there is no joining of two linear backbones. These polymers are useful as antimicrobials, flocculating agents, antistatic agents, electroconductive agents for coating paper, chelating agents and bile acid binding agents, as well as in similar applications where their high charge to weight ratio and fully accessible nitrogen atoms can be employed. The polymers are obtained by the polymerization of dihydro-oxazine, reductive alkylation of the resulting polymer, followed by quaternization.
Type:
Grant
Filed:
April 11, 1979
Date of Patent:
June 3, 1980
Assignee:
Merck & Co., Inc.
Inventors:
Arthur F. Wagner, Nathaniel Grier, Tsung-Ying Shen
Abstract: Novel polymers having a linear backbone which is free from both branching and cross-linking, comprising quaternized nitrogen atoms linked to each other through trimethylene groups. By the term "linear backbone" is meant that the polymer has only acyclic groups, i. e. trimethylene, linking the nitrogen atoms in a single continuous chain; the polymer is free from "branching" when it has no repeating monomer units extending from the polymer backbone; and it is free from "cross-linking" when there is no joining of two linear backbones. These polymers are useful as antimicrobials, flocculating agents, antistatic agents, electroconductive agents for coating paper, chelating agents and bile acid binding agents, as well as in similar applications where their high charge to weight ratio and fully accessible nitrogen atoms can be employed. The polymers are obtained by the polymerization of dihydro-oxazine, reductive alkylation of the resulting polymer, followed by quaternization.
Type:
Grant
Filed:
April 11, 1979
Date of Patent:
May 27, 1980
Assignee:
Merck & Co., Inc.
Inventors:
Arthur F. Wagner, Nathaniel Grier, Tsung-Ting Shen
Abstract: The novel compound 7-methyl-8-methylamino-10-(1'-D-ribityl)isoalloxazine is prepared. This compound has anticoccidial, antiprotozoal and antiparasitic activity. It is particularly useful for controlling cecal and/or intestinal coccidiosis when administered in minor quantities to animals, in particular to poultry, usually in admixture with animal sustenance.
Abstract: An efficient method has been found for the removal of the 3-isomer present in crude 9-(2-chloro-6-fluorobenzyl)adenine. Crude 9-(2-chloro-6-fluorobenzyl)adenine is transalkylated in sulfuric acid-toluene to reduce the 3-isomer to undetectable levels (<100 ppm). Alternately, crude 9-(3-chloro-6-fluorobenzyl)adenine is first treated with dilute nitric acid to remove the bulk of the 3-isomer followed by transalkylation to sulfuric acid-toluene to reduce the 3-isomer to undetectable levels (<100 ppm). The overall yield for this purification is about 95% based on the 9-(2-chloro-6-fluorobenzyl)adenine content of the crude material. The resulting pure 9-(2-chloro-6-fluorobenzyl)adenine has anticoccidial activity and is useful in controlling cecal and/or intestinal coccidiosis when administered in minor quantities to animals, in particular to poultry usually in admixture with animal sustenance.
Type:
Grant
Filed:
June 16, 1978
Date of Patent:
October 16, 1979
Assignee:
Merck & Co., Inc.
Inventors:
Ichiro Shinkai, Leonard M. Weinstock, Roger J. Tull
Abstract: A novel peptide designated anthopleurin-B, hereinafter also referred to as AP-B, obtained from the sea anemone Anthopleura xanthogrammica is found to possess cardiotonic activity.
Type:
Grant
Filed:
May 3, 1978
Date of Patent:
August 28, 1979
Assignee:
University of Hawaii
Inventors:
Ted R. Norton, Shoji Shibata, Midori Kashiwagi
Abstract: Somatostatin analogs having the structural formula:Cyclo[(X).sub.j -(A).sub.k -(B).sub.1 -Phe-Phe-(D- or L-)Trp-Lys-Thr-Phe-Thr-(C).sub.m ]WhereinX is ##STR1## and n=0 to 4; A is Lys, (.epsilon.-INOC) Lysine;B is Asn, Ala, .alpha.-aminobutyric acid;C is Ser, Gly;J, k, l and m are 0 to 1; with the proviso that j, k, l, and m are not all 1 and not all 0,Wherein the ring formed by the peptide backbone contains 24 to 33 atoms and the pharmaceutically acceptable non-toxic acid addition salts thereof are prepared by the solid phase method. These peptides have the property of inhibiting release of insulin, decreasing gastric secretion, inhibiting growth hormone release and inhibiting glucagon release in humans and animals.
Type:
Grant
Filed:
April 7, 1978
Date of Patent:
July 24, 1979
Assignee:
Merck & Co., Inc.
Inventors:
Robert G. Strachan, William J. Paleveda, Daniel F. Veber, Frederick W. Holly
Abstract: Somatostatin analogs having the structural formula: ##STR1## are prepared by controlled stepwise procedures starting with individual amino acid components. These peptides have the property of lowering blood glucose, inhibiting gastric secretion, inhibiting growth hormone release and inhibiting glucagon release in humans and animals.
Type:
Grant
Filed:
June 14, 1976
Date of Patent:
July 17, 1979
Assignee:
Merck & Co., Inc.
Inventors:
Daniel F. Veber, Frederick W. Holly, Robert G. Strachan, William J. Paleveda, Ruth F. Nutt, Ralph F. Hirschmann
Abstract: Novel polymers having a linear backbone which is free from both branching and cross-linking, comprising either tertiary or quaternized nitrogen atoms linked to each other through ethylene groups. These polymers are useful as antimicrobials, flocculating agents, antistatic agents, electroconductive agents for coating paper, chelating agents and bile acid binding agents, as well as in similar applications where their high charge to weight ratio and fully accessible nitrogen atoms can be employed. The polymers are obtained by the polymerization of an oxazoline, hydrolysis or direct reduction, nitrogen substitution, and optional quaternization of the resulting polymer.
Type:
Grant
Filed:
September 29, 1977
Date of Patent:
July 17, 1979
Assignee:
Merck & Co., Inc.
Inventors:
Arthur F. Wagner, Nathaniel Grier, Tsung-Ying Shen
Abstract: Novel linear, unbranched, non-cross-linked polymers particularly poly-[{methyl-(3-trimethylammoniopropyl)iminio}trimethylene dihalide] are prepared by the polymerization of the novel monomer, 3-[N'-(3-halopropyl)-N'-methylamino]-N,N,N-trimethyl-1-propanaminium halide, or an acid addition salt thereof preferably in an oxygen excluded environment, e.g., under nitrogen or argon. The polymer, especially after modification of terminal groups, is an excellent oral anticholesterolemic.
Abstract: Nitroarginyl peptides are selectively reduced to the corresponding arginyl peptides by titanium (III). The nitro protecting group which is labile toward nucleophilic reagents is retained through part of a synthesis and selectively removed prior to treatment with nucleophiles such as hydrazine and ammonia. The selectivity of titanium (III) for removal of the nitro functionality increases the flexibility of this protecting group in the synthesis of arginyl peptides. The present novel process is useful in the synthesis of medicinal peptides such as molluscan cardiac stimulant H-Phe-Met-Arg-Phe-NH.sub.2.
Abstract: The novel thymic factor polypeptide hormone, elaborated by the thymus and und in the blood serum, is isolated. The hormone is useful for the treatment of autoimmune diseases and for selectively stimulating T-cell activity in aging subjects.
Type:
Grant
Filed:
April 25, 1978
Date of Patent:
April 10, 1979
Assignee:
Institute National de la Sante & de la Recherche Medicale (INSERM)
Abstract: Somatostatin analogs having the structural formula: ##STR1## wherein A is Phe, Tyr, O-Me-Tyr,B is Phe, Tyr,C is Thr, Val,R is H or COOH,wherein the ring formed by the peptide backbone contains 26 atoms and pharmaceutically acceptable non-toxic acid addition salts and carboxylic acid salts thereof are prepared by the solid phase method. These peptides have the property of inhibiting release of insulin, inhibiting growth hormone release and inhibiting glucagon release in humans and animals without materially affecting gastric secretion.
Abstract: Dihydroxybenzisoxazolin-3-yl-substituted-1-methyl-5-nitroimidazoles having the hydroxy- groups on adjacent 4,5-; 5,6- or 6,7-positions of the isoxazolin group. These compounds have antibacterial and antiprotozoal activity in humans and animals. They are particularly active against trypanosomiasis and trichomoniasis.
Abstract: The antibiotics MSD 890A.sub.2 and MSD 890A.sub.5 and pharmaceutically acceptable salts thereof (hereinafter referred to as antibiotics 890A.sub.2 and 890A.sub.5) are active against both gram-positive and gram-negative bacteria. The antibiotics are produced by growing species of Streptomyces on suitable fermentation media.
Type:
Grant
Filed:
August 5, 1977
Date of Patent:
February 27, 1979
Assignee:
Merck & Co., Inc.
Inventors:
Patrick J. Cassidy, Robert T. Goegelman, Edward O. Stapley, Sebastian Hernandez
Abstract: Bicyclic somatostatin analogs and pharmaceutically acceptable non-toxic acid addition salts thereof are prepared by the solid phase method. These analogs have the property of inhibiting the release of growth hormone without affecting the level of gastric secretions or without affecting the level of gastric secretions, insulin and glucagon in humans and animals. The compounds are particularly useful in the treatment of acromegaly and diabetic retinopathy. Due to the bicyclic structure, these analogs are resistant to enzymatic metabolism and have a longer duration of activity than somatostatin.
Abstract: Bicyclic somatostatin analogs and pharmaceutically acceptable non-toxic acid addition salts thereof are prepared by the solid phase method. These analogs have the property of inhibiting the release of insulin, glucagon and growth hormone in humans and animals. The compounds are particularly useful in the treatment of diabetes. Due to the bicyclic structure, these analogs are resistant to enzymatic metabolism and have a longer duration of activity.
Abstract: The novel thymic factor polypeptide hormone, elaborated by the thymus and und in the blood serum, is isolated. The hormone is useful for the treatment of autoimmune diseases and for selectively stimulating T-cell activity in aging subjects.
Type:
Grant
Filed:
September 22, 1976
Date of Patent:
January 9, 1979
Assignee:
Institut National de la Sante et de la Recherche Medicale (Inserm)
Abstract: Somatostatin analog, hereinafter designated des(Ala.sup.1 -Gly.sup.2)desaminocys.sup.3 -somatostatin, having the structure: ##STR1## is prepared by controlled stepwise procedures starting with individual amino acid components. This peptide has the property of lowering blood glucose, inhibiting gastric secretion and inhibiting growth hormone release in humans and animals.
Type:
Grant
Filed:
April 8, 1975
Date of Patent:
December 19, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Frederick W. Holly, William J. Paleveda, Robert G. Strachan, Daniel F. Veber
Abstract: Novel substituted benzoylacrylanilides are prepared by reacting a substituted benzoylacrylic acid with a substituted aniline in the presence of a coupling agent. These acrylanilides have significant anticoccidial activity.
Type:
Grant
Filed:
June 30, 1977
Date of Patent:
December 19, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Peter Kulsa, Dale R. Hoff, Helmut H. Mrozik
Abstract: 9-(Dihalobenzyl)adenines are prepared uncontaminated with other positional isomers in a series of mild transformations starting from 4,5,6-triaminopyrimidine and proceeding via 7-(N-formyl-N-dihalobenzyl)-amino[1,2,5]thiadiazolo[3,4-d]pyrimidine. The resulting compounds have anticoccidial activity and are useful in controlling cecal and/or intestinal coccidiosis when administered in minor quantities to animals, in particular to poultry usually in admixture with animal sustenance.
Type:
Grant
Filed:
November 21, 1977
Date of Patent:
November 28, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Roger J. Tull, George D. Hartman, Leonard M. Weinstock