Abstract: 2,3-Dihydro-6,7-disubstituted-5-(acyl)benzofuran-2-carboxylic acids, the pharmaceutically acceptable salt, ester and amide derivatives thereof and combinations of these compounds with antikaluretic agents are disclosed having diuretic-saluretic, uricosuric and antihypertensive activity.
Type:
Grant
Filed:
January 27, 1978
Date of Patent:
August 7, 1979
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr.
Abstract: Nuclear substituted 2-hydroxyphenylmethanesulfamic acids and their pharmaceutically acceptable salts wherein the phenyl nucleus is substituted with 2 to 4 nuclear substituents and which are useful saluretic-diuretics and anti-inflammatories are disclosed. The products may be prepared by reacting nuclear substituted salicylaldehydes with ammonium sulfamate to generate intermediate imines which are reduced to afford the compounds of this invention.
Type:
Grant
Filed:
November 23, 1977
Date of Patent:
June 26, 1979
Assignee:
Merck & Co., Inc.
Inventors:
Robert L. Smith, Gerald E. Stokker, Edward J. Cragoe, Jr.
Abstract: 6,7-Disubstituted-5-(acyl)benzofuran-2-carboxylic acids, the pharmaceutically acceptable salt, ester and amide derivatives thereof and combinations of these compounds with antikaluretic agents are disclosed having diuretic-saluretic, uricosuric and antihypertensive activity.
Type:
Grant
Filed:
December 5, 1977
Date of Patent:
May 15, 1979
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr., William F. Hoffman
Abstract: The case involves novel pyrazine-2-carbonyloxyguanidines and processes for preparing same. The pyrazine-2-carbonyloxyguanidines are eukalemic or antikaliuretic agents possessing diuretic and natriuretic properties.
Type:
Grant
Filed:
January 9, 1978
Date of Patent:
March 20, 1979
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr., Mark G. Bock
Abstract: The case involves novel N-pyrazinecarbonyl-N'-acylguanidines and processes for preparing same. The N-pyrazinecarbonyl-N'-acylguanidines are eukalemic agents possessing diuretic and natriuretic properties.
Type:
Grant
Filed:
September 16, 1977
Date of Patent:
February 20, 1979
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr.
Abstract: Certain substituted 4-aminomethyl-3-pyridinols and their pharmaceutically acceptacle acid addition salts wherein the pyridinol nucleus may be further substituted with 1 to 2 nuclear substituents are useful as antihypertensive, diuretic and saluretic agents. These products may be prepared by halogenating an appropriately substituted pyridine salt.
Type:
Grant
Filed:
May 26, 1977
Date of Patent:
October 31, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Robert L. Smith, Gerald E. Stokker, Edward J. Gragoe, Jr.
Abstract: 2,3-Dichloro-4-[(substituted sulfonyl)phenoxyl]-acetic acids and their salt, ester and amide derivatives thereof. The products are useful diuretic, saluretic and uricosuric agents. The acid products are prepared by treating a 2,3-dichloro-4-(2-substituted sulfonyl)phenol with a haloalkanoic acid or ester thereof and if the ester is employed hydrolyzing the ester.
Type:
Grant
Filed:
June 17, 1977
Date of Patent:
September 19, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr.
Abstract: The case involves novel N-pyrazinecarbonyl-N'-substituted-sulfamoylguanidine and processes for preparing same. The N-pyrazinecarbonyl-N'-substituted-sulfamoylguanidines are excellent eukalemic agents possessing diuretic and natriuretic properties.
Type:
Grant
Filed:
March 4, 1977
Date of Patent:
September 19, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr.
Abstract: Substituted 2-aminomethylphenyl sulfamates and pharmaceutically acceptable acid addition salts wherein the sulfamate group is N-substituted with up to 2 groups and the phenyl nucleus is further substituted by from 2 to 4 nuclear substituents which are useful as diuretics and saluretics are disclosed. The products may be prepared by reacting a N-protected substituted 2-aminomethylphenol with a substituted sulfamoyl chloride to generate an intermediate which is N-deblocked to give the compounds of this invention.
Type:
Grant
Filed:
September 16, 1977
Date of Patent:
September 12, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Robert L. Smith, Gerald E. Stokker, Edward J. Cragoe, Jr.
Abstract: Compositions useful in the treatment of gout and hyperuricemia and containing a substituted 1,2,4-triazole as the active ingredient are provided, the triazoles being substituted at the 5 position with a pyridyl radical and at the 3 position with a phenyl or a pyridyl radical. Methods of preparing these substituted triazoles are described. Certain of the compounds are novel.
Abstract: 5-[Hydroxy(substituted)methyl]-2,3-dihydrobenzo-furan-2-carboxylic acids, the pharmaceutically acceptable salt, ester and amide derivatives thereof and combinations of these compounds with antikaluretic agents are disclosed having diuretic-saluretic, uricosuric and antihypertensive activity.
Type:
Grant
Filed:
December 6, 1976
Date of Patent:
July 11, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr., William Hoffman
Abstract: [1-Oxo-2-aryl or thienyl-2-substituted-5-indanyloxy (or thio)]aklanoic acid, derivatives thereof, their salts, esters and amides are disclosed. The products display a dual pharmaceutical utility in that they exhibit diuretic, saluretic and uricosuric activity. Also disclosed are processes for the preparation of such [1-oxo-2-aryl or thienyl-2-substituted-5-indanyloxy (or thio)]alkanoic acids, pharmaceutical compositions comprising therapeutically effective amounts of such compounds and methods of treatment comprising administering such compounds and compositions.
Type:
Grant
Filed:
June 10, 1975
Date of Patent:
June 20, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr.
Abstract: This invention is concerned with (3-amino-5-substituted-6-fluoropyrazinoyl or pyrazinamido)guanidine compounds and derivatives thereof bearing substituents on the guanidine nitrogens. These compounds possess useful natriuretic properties. Also included are processes for preparing these compounds and a novel intermediate used in the preparation of these compounds.
Type:
Grant
Filed:
July 23, 1976
Date of Patent:
May 2, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr.
Abstract: 2,3-Dihydro-6,7-disubstituted-5-(acyl)benzofuran-2-carboxylic acids, the pharmaceutically acceptable salt, ester and amide derivatives thereof and combinations of these compounds with antikaluretic agents are disclosed having diuretic-saluretic, uricosuric and antihypertensive activity.
Type:
Grant
Filed:
April 20, 1976
Date of Patent:
May 2, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr.
Abstract: 6,7-Disubstituted-5-(acyl)benzofuran-2-carboxylic acids, the pharmaceutically acceptable salt, ester and amide derivatives thereof and combinations of these compounds with antikaluretic agents are disclosed having diuretic-saluretic, uricosuric and antihypertensive activity.
Type:
Grant
Filed:
October 18, 1976
Date of Patent:
April 18, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr., William F. Hoffman
Abstract: The case involves novel pyrazinecarboxamides and processes for preparing same. The pyrazinecarboxamides are excellent eukalemic agents possessing diuretic and natriuretic properties.
Type:
Grant
Filed:
September 13, 1976
Date of Patent:
April 18, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr., Charles N. Habecker
Abstract: 1-Oxo-2,2-disubstituted-5-indanyloxy(or thio)alkanoic acids and their salt, ester, anhydride, amide and 5-tetrazolyl derivatives are disclosed. The products display a dual pharmaceutical utility in that they exhibit diuretic, saluretic and uricosuric activity. The acid products are prepared by treating a 2,2-disubstituted-5-hydroxy(or mercapto)-1-indanone with an haloalkanoic acid or ester thereof and, if the ester is employed, hydrolyzing the ester.
Type:
Grant
Filed:
July 13, 1976
Date of Patent:
April 18, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr.
Abstract: 1-Oxo-2,2-disubstituted-5-indanyloxy(or thio)alkanoic acids and their salt, ester, anhydride, amide and 5-tetrazolyl derivatives are disclosed. The products display a dual pharmaceutical utility in that they exhibit diuretic, saluretic and uricosuric activity. The acid products are prepared by treating a 2,2-disubstituted-5-hydroxy(or mercapto)-1-indanone with an haloalkanoic acid or ester thereof and, if the ester is employed, hydrolyzing the ester.
Type:
Grant
Filed:
July 13, 1976
Date of Patent:
March 28, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr.
Abstract: [1-Oxo-2-halo(or hydrogen)indanyloxy(or thio)]-alkanoic acid products and salts, esters and amide derivatives where the indanyl ring may be further substituted with from 2 to 5 nuclear substituents. The [1-oxo-2-haloindanyloxy-(or thio)]alkanoic acids are prepared (1) via the halogenation of a [1-oxoindanyloxy(or thio)]alkanoic acid or (2) via the addition of halogen to a [1-oxoindenyloxy(or thio)]-alkanoic acid. The [1-oxoindanyloxy(or thio)]alkanoic acids are prepared (1) via cyclialkylation of a (2-alkylideneacyl)-phenoxy(or thio)alkanoic acid or (2) via etherification of a hydroxy(or mercapto)-2-alkyl-1-indanone. The [1-oxo-2-halo(or hydrogen)indanyloxy(or thio)]alkanoic acids are diuretics and saluretics. In addition, some of these compounds are also able to maintain the uric acid concentration in the body at pretreatment level or to cause a decrease in uric acid concentration.
Type:
Grant
Filed:
May 5, 1976
Date of Patent:
January 24, 1978
Assignee:
Merck & Co., Inc.
Inventors:
Edward J. Cragoe, Jr., Otto W. Woltersdorf, Jr.