The Two Cyclos Share At Least Three Ring Members (i.e., Bridged) Patents (Class 549/463)
  • Patent number: 4906280
    Abstract: T-butylhydrazides of carboxylic acid anhydrides and carboxylic acid chlorides useful as plant growth regulants in the free acid form or their equivalent salts.
    Type: Grant
    Filed: October 14, 1987
    Date of Patent: March 6, 1990
    Assignee: Pennwalt Corporation
    Inventors: Stanley R. Sandler, Shyam B. Advani
  • Patent number: 4883888
    Abstract: Oxa-fenchols and oxa-fenchyl amines are disclosed which are useful in the preparation of high intensity sweeteners. These sweeteners can be used to sweeten a variety of foods, beverages and other oral products. The oxa-fenchols also have a pine-like fragrance which makes them potentially useful as a perfume ingredient.
    Type: Grant
    Filed: July 13, 1984
    Date of Patent: November 28, 1989
    Assignee: The Procter & Gamble Company
    Inventor: John M. Gardlik
  • Patent number: 4883809
    Abstract: 7-Oxabicycloheptane imino interphenyleneoxy substituted prostaglandin analogs are provided having the structural formula ##STR1## wherein n is 1 or 2;R is H; lower alkyl, or alkali metal; andR.sup.1 is --OR.sup.2, ##STR2## where R.sup.2 is lower alkyl, aryl, aralkyl, alkanoyl or aroyl; andR.sup.3 is lower alkyl, aryl, aralkyl, alkoxy, aryloxy, aralkoxy, --NHaralkyl, --NHalkyl or --NHaryl. The compounds are useful in the treatment of thrombotic disease.
    Type: Grant
    Filed: November 17, 1988
    Date of Patent: November 28, 1989
    Inventor: Raj N. Misra
  • Patent number: 4883811
    Abstract: 7-Oxabicycloheptane imino interphenylene substituted prostaglandin analogs are provided having the structural formula ##STR1## wherein n is 1 or 2; m is 1 or 2; R is H, lower alkyl, or alkali metal; and R.sup.1 is --OR.sup.2, ##STR2## where R.sup.2 is lower alkyl, aryl, aralkyl, cycloalkylalkyl, alkanoyl or aroyl; and R.sup.3 is lower alkyl, aryl, aralkyl, alkoxy, aryloxy, aralkoxy, --NHaralkyl, --NHalkyl, --NHalkylcycloalkyl or --NHaryl.These compounds are cardiovascular agents which exhibit thromboxane antagonist activity and thus are useful in the treatment of thrombotic and vasospastic disease.
    Type: Grant
    Filed: November 17, 1988
    Date of Patent: November 28, 1989
    Inventors: Raj N. Misra, Steven E. Hall
  • Patent number: 4861913
    Abstract: Bicyclic sulfonamido derivatives represented by the formula: ##STR1## wherein R.sub.1 is a hydrogen or lower alkyl; R.sub.2 is an alkyl, substituted or unsubstituted aryl, aralkyl or heterocycle; R.sub.3 is a hydrogen or methyl; X is an alkylene or alkenylene which may be substituted by a fluorine atom or atoms an may contain an oxygen, sulfur and/or phenylene in the chain; Y is straight or branched alkylene or alkenylene, oxygen, or sulfur; m is 0 or 1; and n is 0, 1 or 2, or their salt, said derivatives being useful as antithrombotic, anti-vasoconstricting, and anti-bronchoconstricting drugs.
    Type: Grant
    Filed: November 5, 1986
    Date of Patent: August 29, 1989
    Assignee: Shionogi & Co., Ltd.
    Inventors: Masayuki Narisada, Mitsuaki Ohtani, Fumihiko Watanabe, Sanji Hagishita, Kaoru Seno, Susumu Kamata, Nobuhiro Haga, Tatsuo Tsuri, Tadahiko Tsushima, Kenji Kawada
  • Patent number: 4851553
    Abstract: A process is provided for preparing a 7-oxabicycloheptane amino alcohol intermediate of the general structure ##STR1## which is useful in preparing thromboxane A.sub.2 receptor antagonists. This intermediate is prepared by reacting mesoanhydride with an aryl amine ##STR2## wherein R is alkyl, CH.sub.2 OH, CO.sub.2 H or CO.sub.2 alkyl, to form the acid ##STR3## which is reduced by treatment with lithium aluminum hydride or diisobutylaluminum hydride or Red-Al to form the alcohol ##STR4## wherein R.sup.1 is CH.sub.2 OH when R is CO.sub.2 H, CO.sub.2 alkyl or CH.sub.2 OH, and R.sup.1 is alkyl when R is alkyl; where in the above alcohol R.sup.1 is CH.sub.2 OH, such alcohol compound is treated with an alkyl chloroformate in the presence of base such as an alkali metal alkoxide to form the alcohol ##STR5## which undergoes cleavage by treatment with alkali metal, ammonia and acid to form the amino alcohol intermediate.Where in the above alcohol R.sup.
    Type: Grant
    Filed: November 28, 1988
    Date of Patent: July 25, 1989
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: John K. Thottathil
  • Patent number: 4837234
    Abstract: Novel compounds have a formula (I) ##STR1## wherein ##STR2## represents a bicyclo [2,2,1] hept-2Z-ene, bicyclo [2,2,1] heptane, 7-oxa-bicyclo [2,2,1] hept-2Z-ene, 7-oxa-bicyclo [2,2,1] heptane, bicyclo [2,2,2] oct-2Z-ene or bicyclo [2,2,2] octane substituted at the 5-position by the group R.sup.1 and at the 6-position by the group ANR.sup.2 R, a 6,6-dimethyl-bicyclo [3,1,1] heptane substituted at the 2-position by the group R.sup.1 and at the 3-position by the group ANR.sup.2 R or at the 2-position by the group ANR.sup.2 R and at the 3-position by the group R.sup.1, a cyclohex-1-ene or cyclohexane substituted at the 4-position by the group R.sup.1 and at the 5-position by the group ANR.sup.2 R or a 1-hydroxycyclopentane substituted at the 2-position by the group R.sup.1 and at the 2-position by the group ANR.sup.2 R, R.sup.
    Type: Grant
    Filed: July 22, 1986
    Date of Patent: June 6, 1989
    Assignee: National Research Development Corporation
    Inventors: Robert L. Jones, Norman H. Wilson
  • Patent number: 4831163
    Abstract: A method is provided for preparing cineole in an improved yield and with increased 1,4- isomer content, by reaction of terpin hydrate or terpineol with an acid, such as phosphoric acid, with distillation of the cineole from the reaction mixture as the cineole is formed.
    Type: Grant
    Filed: July 24, 1987
    Date of Patent: May 16, 1989
    Assignee: Union Camp Corporation
    Inventor: Peter W. D. Mitchell
  • Patent number: 4816579
    Abstract: A process is provided for preparing a 7-oxabicycloheptane amino alcohol intermediate of the general structure ##STR1## (wherein the above structure represents (D) of (L) isomers) which is useful in preparing thromboxane A.sub.2 receptor antagonists. This intermediate is prepared by reacting mesoanhydride with an aryl amine ##STR2## wherein R is alkyl, CH.sub.2 OH, CO.sub.2 H or CO.sub.2 alkyl, to form the acid ##STR3## which is reduced by treatment with lithium aluminum hydride or diisobutylaluminum hydride or Red-Al to form the alcohol ##STR4## wherein R.sup.1 is CH.sub.2 OH when R is CO.sub.2 H, CO.sub.2 alkyl or CH.sub.2 OH, and R.sup.1 is alkyl; where in the above alcohol R.sup.1 is CH.sub.2 OH, such alcohol compound is treated with an alkyl chloroformate in the presence of base such as an alkali metal alkoxide to form the alcohol ##STR5## which undergoes cleavage by treatment with alkali metal, ammonia and acid to form the amino alcohol intermediate.Where in the above alcohol R.sup.
    Type: Grant
    Filed: January 27, 1988
    Date of Patent: March 28, 1989
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: John K. Thottathil
  • Patent number: 4788305
    Abstract: Compounds of the formula ##STR1## wherein A is a hydrocarbon chain containing 1 to 16 groups, the said chain containing at least one heteroatom, at least one unsaturation, the assembly of the group constituting the chain may be a mono- or polycyclic system including a spiro or endosystem and the assembly of chain A and the carbon atoms attached thereto can contain at least one chiral atom or the hemiacetal moiety thereto which can present a chirality due to the dissymetric spatial configuration of the molecule and Y is selected from the group consisting of hydrogen, alkyl of 1 to 18 carbon atoms optionally substituted, --CY.sub.3 ' and the .beta.,.gamma. bond together with Y can be part of A and Y' is bromine or chlorine.
    Type: Grant
    Filed: July 17, 1987
    Date of Patent: November 29, 1988
    Assignee: Roussel Uclaf
    Inventors: Jean Tessier, Jean-Pierre Demoute
  • Patent number: 4775679
    Abstract: Phenylalkyl-2,3-dihydrobenzofurans and analogs were prepared by (1) nucleophilic substitution involving an appropriately substituted 2,3-dihydrobenzofuranol (or 2,3-dihydrobenzopyranol) and a cinnamylhalide followed by reduction; or (2) by Wittig reaction involving a halomethyl derivative of 2,3-dihydrobenzofuran (or 2,3-dihydrobenzopyran and an aryl or a heteroaryl aldehyde followed by reduction. These compounds were found to be potent anti-inflammatory agents.
    Type: Grant
    Filed: May 4, 1987
    Date of Patent: October 4, 1988
    Assignee: Merck & Co., Inc.
    Inventors: Michael N. Chang, David A. Boulton, Kathryn L. Thompson
  • Patent number: 4743697
    Abstract: A process is provided for preparing a 7-oxabicycloheptane amino alcohol intermediate of the general structure ##STR1## which is useful in preparing thromboxane A.sub.2 receptor antagonists. This intermediate is prepared by reacting mesonhydride with an aryl amine ##STR2## wherein R is alkyl, CH.sub.2 OH, CO.sub.2 H or CO.sub.2 alkyl, to form the acid ##STR3## which is reduced by treatment with lithium aluminum hydride or diisobutylaluminum hydride or Red-Al to form the alcohol ##STR4## wherein R.sup.1 is CH.sub.2 OH when R is CO.sub.2 H, CO.sub.2 alkyl or CH.sub.2 OH, and R.sup.1 is alkyl when R is alkyl; where in the above alcohol R.sup.1 is CH.sub.2 OH, such alcohol compound is treated with an alkyl chloroformate in the presence of base such as an alkali metal alkoxide to form the alcohol ##STR5## which undergoes cleavage by treatment with alkali metal, ammonia and acid to form the amino alcohol intermediate.Where in the above alcohol R.sup.
    Type: Grant
    Filed: May 21, 1987
    Date of Patent: May 10, 1988
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: John K. Thottathil
  • Patent number: 4738978
    Abstract: Bisthioamide-7-oxabicycloheptane prostaglandin analogs are provided having the structural formula ##STR1## wherein A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; R is CO.sub.2 H, CO.sub.2 lower alkyl or ##STR2## q is 1 to 12; and R.sup.1 is H, lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, lower alkoxy, aryloxy, arylalkyloxy, amino, alkylamino arylamino, arylalkylamino, lower alkyl-S-aryl-S-, arylalkyl-S-, ##STR3## (wherein n' is 0, 1 or 2), alkylaminoalkyl, arylaminoalkyl, arylalkylaminoalkyl, alkoxyalkyl, aryloxyalkyl or arylalkoxyalkyl.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: November 10, 1986
    Date of Patent: April 19, 1988
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Masami Nakane, Joyce Reid
  • Patent number: 4734425
    Abstract: 7-Oxabicycloheptane substituted hydroxamic acid prostaglandin analogs are provided having the structural formula ##STR1## wherein A is --CH.dbd.CH-- or --CH.sub.2 -CH.sub.2 --; n is 1 to 5; R is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, --CH.sub.2 OH, ##STR2## wherein R.sup.4 and R.sup.5 are the same or different and are H, lower alkyl, hydroxy, lower alkoxy or aryl, at least one of R.sup.4 and R.sup.5 being other than hydroxy and lower alkoxy; q is 1 to 12, R.sup.1 is H or OH; R.sup.2 is OH or H, provided that one of R.sup.1 and R.sup.2 is OH and the other is H; and R.sup.3 is H, lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, lower alkoxy, aryloxy, arylalkyloxy, amino, alkylamino arylamino, arylalkylamino, ##STR3## (wherein n' is 0, 1 or 2), alkylaminoalkyl, arylaminoalkyl, arylalkylaminoalkyl, alkoxyalkyl, aryloxyalkyl or arylalkoxyalkyl.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: October 17, 1986
    Date of Patent: March 29, 1988
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Masami Nakane, Joyce Reid
  • Patent number: 4707494
    Abstract: 7-Oxabicyclo(2.2.1)heptane analogs are disclosed having the general formula ##STR1## wherein R.sub.1 is lower alkyl, alkenyl, substituted alkenyl or alkynyl; R.sub.2 is lower alkyl, alkenyl or alkynyl; A is --CH.sub.2 --CH.dbd.CH-- or a single bond; X is --CH.sub.2, --CH(CH.sub.3) or --C(CH.sub.3).sub.2 ; n is an integer from 0 to 9, with the proviso that when A is a single bond, n is an integer from 1 to 9; including all stereoisomers.These new compounds have been found to be inhibitors of arachidonic acid cyclooxygenase and are therefore useful as antiinflammatory antipyretic and analgesic agents.
    Type: Grant
    Filed: August 26, 1986
    Date of Patent: November 17, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Ravi K. Varma, Carl P. Ciosek, Eric M. Gordon
  • Patent number: 4695586
    Abstract: 7-Oxabicyclo(2.2.1)heptane-based N-hydroxy-N-alkyl (or aryl) ureas, carbamic acids and carbamothioic acids are disclosed having the general formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl, alkenyl, aryl or aralkyl; R.sub.2 is hydrogen, lower alkyl, aralkyl, alkanoyl or aroyl; R.sub.3 is lower alkyl, alkenyl or alkynyl; A is --CH.sub.2 --CH.dbd.CH-- or a single bond; X is oxygen, sulfur or NH; n is an integer from 1 to 8; and all stereoisomers thereof.These new compounds have been found to simultaneously inhibit the enzymes arachidonic acid cyclooxygenase and arachidonic acid 5-lipoxygenase and are therefore useful as antiinflammatory, antiasthma and antipsoriatic agents.
    Type: Grant
    Filed: September 23, 1986
    Date of Patent: September 22, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Ravi K. Varma, Sam T. Chao, Eric M. Gordon
  • Patent number: 4695585
    Abstract: A compound of the formula ##STR1## wherein R.sub.1 is hydrogen, hydroxy, alkoxy or aryloxy; R.sub.2 is hydrogen, hydroxy, alkoxy or aryloxy; or wherein R.sub.1 and R.sub.2 taken together is an aromatic ring; R.sub.3 is hydrogen or lower alkyl; R.sub.4 is lower alkyl, substituted alkyl, alkenyl or alkynyl; X is amino, alkylamino, alkanoylamino, oxygen or a single bond; A is CH.sub.2 --CH.dbd.CH or a single bond; and n is an integer from 0 to 9, with the proviso that when A is a single bond, n is an integer from 1 to 9 including all stereoisomers thereof.These new compounds have been found to simultaneously inhibit the arachidonic acid enzymes 5-lipoxygenase and cyclooxygenase and as such are useful, for example, as antiinflammatory agents.
    Type: Grant
    Filed: September 23, 1986
    Date of Patent: September 22, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Ravi K. Varma, Eric M. Gordon
  • Patent number: 4687865
    Abstract: A process is provided for preparing a 7-oxabicycloheptane amino alcohol intermediate of the general structure ##STR1## (wherein the above structures represents (D) or (L) isomers) which is useful in preparing thromboxane A.sub.2 receptor antagonists. This intermediate is prepared by reacting mesoanhydride with an aryl amine ##STR2## wherein R is alkyl, CH.sub.2 OH, CO.sub.2 H or CO.sub.2 alkyl, to form the acid ##STR3## which is reduced by treatment with lithium aluminum hydride or diisobutylaluminum hydride or Red-Al to form the alcohol ##STR4## wherein R.sup.1 is CH.sub.2 OH when R is CO.sub.2 H, CO.sub.2 alkyl or CH.sub.2 OH, and R.sup.1 is alkyl when R is alkyl; where in the above alcohol R.sup.1 is CH.sub.2 OH, such alcohol compound is treated with an alkyl chloroformate in the presence of base such as an alkali metal alkoxide to form the alcohol ##STR5## which undergoes cleavage by treatment with alkali metal, ammonia and acid to form the amino alcohol intermediate.Where in the above alcohol R.sup.
    Type: Grant
    Filed: June 4, 1986
    Date of Patent: August 18, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: John K. Thottathil
  • Patent number: 4673685
    Abstract: Hydroximic acids of 7-oxabicycloheptane substituted ether and thioether prostaglandin analogs are provided having the structural formula ##STR1## wherein Y is O or ##STR2## and including all stereoisomers thereof. The compounds are inhibitors of prostaglandin and biosynthesis and as such are useful, for example, as anti-allergy and antiinflammatory agents and also as antipsoriatic agents.
    Type: Grant
    Filed: July 23, 1986
    Date of Patent: June 16, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Ravi K. Varma, Eric M. Gordon, Ligaya M. Simpkins
  • Patent number: 4672075
    Abstract: 7-Oxabicyclo(2.2.1)heptane hydroxamic acid derivatives are disclosed having the general formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl, aryl, aralkyl or alkenyl; R.sub.2 is hydrogen, lower alkyl, alkanoyl or aroyl; R.sub.3 is lower alkyl, alkenyl or alkynyl; A is --CH.sub.2 --CH.dbd.CH-- or a single bond; and n is an integer from 0 to 9, with the proviso that when A is a single bond, n is an integer from 1 to 9; and including all stereoisomers and pharmaceutically acceptable salts thereof.These new compounds have been found to simultaneously inhibit the arachidonic acid enzymes cyclooxygenase and 5-lipoxygenase and are therefore useful as antiinflammatory, antiasthma and antipsoriatic agents.
    Type: Grant
    Filed: August 26, 1986
    Date of Patent: June 9, 1987
    Assignee: E. R. Squibb & Sons
    Inventors: Eric M. Gordon, Ravi K. Varma
  • Patent number: 4670453
    Abstract: 7-Oxabicycloheptane substituted amidocarbamoyl prostaglandin analogs are provided having the structural formula ##STR1## wherein m is 0 to 4; A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; R.sup.1 is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, ##STR2## wherein R.sup.4 and R.sup.5 are the same or different and are H, lower alkyl, hydroxy, lower alkoxy or aryl, at least one of R.sup.4 and R.sup.5 being other than hydroxy and lower alkoxy; p is 1 to 4; X is O or S; R.sup.2 is H or lower alkyl; and R.sup.3 is lower alkyl, lower alkenyl, aryl, arylalkyl, cycloalkyl or cycloalkylalkyl.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: May 8, 1986
    Date of Patent: June 2, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Jagabandhu Das
  • Patent number: 4670041
    Abstract: Compounds of the formula ##STR1## wherein X is (--CR.sub.4 R.sub.4 --).sub.m in which m is 0 or 1;Y is (--CR.sub.5 R.sub.6 --).sub.n in which n is 0, 1 or 2;Z is (--CR.sub.7 R.sub.7 --).sub.p in which p is 1, 2, or 3; the sum of m+n+p is an integer of 2 to 5, inclusive;R.sub.2 and R.sub.3 each is H or alkyl, and the like;R.sub.1 is H or alkyl; andW is an unsaturated moiety, are useful as plant growth regulators and herbicides.
    Type: Grant
    Filed: September 13, 1982
    Date of Patent: June 2, 1987
    Assignee: E. I. du Pont de Nemours and Company
    Inventors: George B. Payne, Samuel B. Soloway, James E. Powell, Steven A. Roman, Willy D. Kollmeyer
  • Patent number: 4663337
    Abstract: 7-Oxabicycloheptane substituted amides are provided having the structural formula ##STR1## wherein m is 0 to 4; A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; R is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, ##STR2## wherein R.sup.4 and R.sup.5 are the same or different and are H, lower alkyl, hydroxy, lower alkoxy or aryl, at least one of R.sup.4 and R.sup.5 being other than hydroxy and lower alkoxy; R.sup.1 is H, lower alkyl or aryl; q is 1 to 6; X is ##STR3## (wherein q is 1) or ##STR4## (wherein R.sup.3 is H or lower alkyl); R.sup.2 is lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, lower alkoxy, aralkyloxy, cycloalkyl or cycloalkylalkyl.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: April 18, 1986
    Date of Patent: May 5, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Jagabandhu Das, Masami Nakane
  • Patent number: 4663336
    Abstract: 7-Oxabicycloheptane substituted amide prostaglandin analogs are provided having the structural formula ##STR1## wherein m is 0 to 4; A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; Q is --CH.dbd.CH--, --CH.sub.2 --, ##STR2## or a single bond; R is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, --CH.sub.2 OH, ##STR3## wherein R.sup.4 and R.sup.5 are the same or different and are H, lower alkyl, hydroxy, lower alkoxy or aryl, at least one of R.sup.4 and R.sup.5 being other than hydroxy and lower alkoxy; p is 1 to 4; R.sup.1 is H or lower alkyl; q is 1 to 12; R.sup.2 is H or lower alkyl; and R.sup.3 is H, lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, lower alkoxy, aryloxy, arylalkyloxy, amino, alkylamino arylamino, arylalkylamino, ##STR4## (wherein n' is 0, 1 or 2), alkylaminoalkyl, arylaminoalkyl, arylalkylaminoalkyl, alkoxyalkyl, aryloxyalkyl or arylalkoxyalkyl.
    Type: Grant
    Filed: April 18, 1986
    Date of Patent: May 5, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Masami Nakane, Joyce Reid
  • Patent number: 4661506
    Abstract: 7-Oxabicycloheptane substituted oxo prostaglandin analogs are provided having the structural formula ##STR1## wherein R.sup.1 is lower alkyl, aryl, aralkyl, cycloalkyl or cycloalkylalkyl, A is --CH.dbd.CH-- or --(CH.sub.2).sub.2 --, n is 1 to 4, m is 1 to 8, and R.sup.2 is ##STR2## wherein R.sup.4 is H or lower alkyl and including all steroisomers thereof.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: November 30, 1984
    Date of Patent: April 28, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Steven E. Hall, Martin F. Haslanger, Ravi K. Varma
  • Patent number: 4658033
    Abstract: New interphenylene prostaglandin (PGH) analogs are prepared by a method which involves reacting a bicyclic olefin, an acetylene compound and a benzylic halide together, in the presence of a palladium(O) catalyst in a single-step synthesis. By this technique a large number of new interphenylene PGH analogs can be prepared, which are useful as inhibitors of arachidonic acid induced platelet aggregation.
    Type: Grant
    Filed: September 23, 1985
    Date of Patent: April 14, 1987
    Assignee: Iowa State University Research Foundation, Inc.
    Inventor: Richard C. Larock
  • Patent number: 4656185
    Abstract: 7-Oxabicycloheptane substituted diacid diamide prostaglandin analogs are provided having the structural formula ##STR1## wherein m is 0 to 4; A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; R is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, --CH.sub.2 OH ##STR2## wherein R.sup.4 and R.sup.5 are the same or different and are H, lower alkyl, hydroxy, lower alkoxy or aryl, at least one of R.sup.4 and R.sup.5 being other than hydroxy and lower alkoxy; p is 1 to 4; R.sup.1 is H or lower alkyl; q is 1 to 12; R.sup.2 and R.sup.3 are the same or different and are H, lower alkly, lower alkenyl, lower alkynyl, aryl, arylalkyl, lower alkoxy, aralkyloxy, cycloalkyl or cycloalkylalkyl.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: December 5, 1985
    Date of Patent: April 7, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Steven E. Hall, Masami Nakane
  • Patent number: 4654367
    Abstract: Hydroxamic acids of 7-oxabicycloheptane substituted ether prostaglandin analogs are provided having the structural formula ##STR1## wherein Q is --CH.sub.2 --A--(CH.sub.2).sub.n --; X is S or O, Y is O or ##STR2## and including all stereoisomers thereof. The compounds are inhibitors of .DELTA..sup.5 -lipoxygenase and inhibitors of prostaglandin and leukotriene biosynthesis and as such are useful, for example, as anti-allergy and antiinflammatory agents and also as antipsoriatic agents.
    Type: Grant
    Filed: February 14, 1986
    Date of Patent: March 31, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Ravi K. Varma, Jagabandhu Das
  • Patent number: 4654364
    Abstract: Hydroxamic acids of 7-oxabicycloheptane substituted ether prostaglandin analogs are provided having the structural formula ##STR1## wherein Y is O or ##STR2## and including all stereoisomers thereof. The compounds are inhibitors of .DELTA..sup.5 -lipoxygenase and inhibitors of prostaglandin and leukotriene biosynthesis and as such are useful, for example, as anti-allergy and antiinflammatory agents and also as antipsoriatic agents.
    Type: Grant
    Filed: November 12, 1985
    Date of Patent: March 31, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Ravi K. Varma, Jagabandhu Das
  • Patent number: 4654355
    Abstract: 7-Oxabicycloheptane substituted amide-thioamide prostaglandin analogs are provided having the structural formula ##STR1## wherein m is 0 to 4; A is --CH.dbd.CH-- or --CH.sub.2 CH.sub.2 --; n is 1 to 5; Q is --CH.dbd.CH--, --CH.sub.2 --, ##STR2## or a single bond; R is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, --CH.sub.2 OH, ##STR3## wherein R.sup.4 and R.sup.5 are the same or different and are H, lower alkyl, hydroxy, lower alkoxy or aryl, at least one of R.sup.4 and R.sup.5 being other than hydroxy and lower alkoxy; p is 1 to 4; R.sup.1 is H or lower alkyl; q is 1 to 12; R.sup.2 is H or lower alkyl; and R.sup.3 is H, lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, lower alkoxy, aralkyloxy, amino, alkylamino, or arylamino.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: August 1, 1985
    Date of Patent: March 31, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Masami Nakane, Joyce Reid
  • Patent number: 4654366
    Abstract: 7-Oxabicycloheptane substituted ether or thio ether prostaglandin analogs are provided having the structural formula ##STR1## wherein A is O or ##STR2## and X is O or ##STR3## and including all stereoisomers thereof. The compounds are inhibitors of .DELTA..sup.5 -lipoxygenase and inhibitors of prostaglandin and leukotriene biosynthesis and as such are useful, for example, as antiallergy and antiinflammatory agents and also as antipsoriatic agents.
    Type: Grant
    Filed: February 14, 1986
    Date of Patent: March 31, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Ravi K. Varma, Jagabandhu Das
  • Patent number: 4654356
    Abstract: 7-Oxabicycloheptane substituted diacid diamide prostaglandin analogs are provided having the structural formula ##STR1## wherein m is 0 to 4; A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; Q is --CH.dbd.CH--, --CH.sub.2 --, ##STR2## or a single bond; R is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, --CH.sub.2 OH, ##STR3## wherein R.sup.4 and R.sup.5 are the same or different and are H, lower alkyl, hydroxy, lower alkoxy or aryl, at least one of R.sup.4 and R.sup.5 being other than hydroxy and lower alkoxy; p is 1 to 4; R.sup.1 is H or lower alkyl; q is 1 to 12; R.sup.2 and R.sup.3 are the same or different and are H, lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, lower alkoxy, aralkyloxy or cycloalkyl.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: August 1, 1985
    Date of Patent: March 31, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Masami Nakane, Joyce Reid
  • Patent number: 4654357
    Abstract: 7-Oxabicycloheptane substituted sulfonamide prostaglandin analogs are provided having the structural formula ##STR1## wherein m is 0 to 4; A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; Q is --CH.dbd.CH--, --CH.sub.2 --, ##STR2## or a single bond; R is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, --CH.sub.2 OH, ##STR3## wherein R.sup.3 and R.sup.4 are the same or different and are H, lower alkyl or aryl; p is 1 to 4; R.sup.1 is H or lower alkyl; and R.sup.2 is H, lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, cycloalkyl or cycloalkylalkyl.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: August 9, 1985
    Date of Patent: March 31, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Masami Nakane
  • Patent number: 4652578
    Abstract: Cis-exo 7-oxabicycloheptane substituted amide prostaglandin analogs are provided having the structural formula ##STR1## wherein A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; R is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, --CH.sub.2 OH, ##STR2## wherein R.sup.2 and R.sup.3 are the same or different and are H, lower alkyl, hydroxy, lower alkoxy or aryl, at least one of R.sup.2 and R.sup.3 being other than hydroxy and lower alkoxy; X is O, NH, CH.dbd.CH, or --(CH.sub.2).sub.x wherein x is 0 or 1; and R.sup.1 is lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, lower alkoxy, aryloxy, amino, alkylamino, arylamino, arylthio or alkylthio.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: February 24, 1986
    Date of Patent: March 24, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Masami Nakane, Steven E. Hall
  • Patent number: 4652576
    Abstract: 7-Oxabicycloheptane substituted amide-carbamide prostaglandin analogs are provided having the structural formula ##STR1## wherein m is 0 to 4; A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; Q is --CH.dbd.CH--, --CH.sub.2 --, ##STR2## or a single bond; R is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, --CH.sub.2 OH, ##STR3## wherein R.sup.3 and R.sup.4 are the same or different and are H, lower alkyl, hydroxy, lower alkoxy or aryl, at least one of R.sup.3 and R.sup.4 being other than hydroxy and lower alkoxy; p is 1 to 5; R.sup.1 is H or lower alkyl; q is 1 to 12; and R.sup.2 is H, lower alkyl, lower alkenyl, lower alkynyl, aryl, or arylalkyl.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: October 18, 1985
    Date of Patent: March 24, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Masami Nakane
  • Patent number: 4647573
    Abstract: 7-Oxabicycloheptane substituted thioamideamide prostaglandin analogs are provided having the structural formula ##STR1## wherein m is 0 to 4; A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; Q is --CH.dbd.CH--, --CH.sub.2 --, ##STR2## or a single bond; R is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, --CH.sub.2 OH, wherein R.sup.4 and R.sup.5 are the same or different and are H, lower alkyl, hydroxy, lower alkoxy or aryl, at least one of R.sup.4 and R.sup.5 being other than hydroxy and lower alkoxy; p is 1 to 4; R.sup.1 is H or lower alkyl; q is 1 to 12; and R.sup.2 R.sup.3 are the same or different and are H, lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, lower alkoxy, aralkyloxy, cycloalkyl or cycloalkylalkyl.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: November 22, 1985
    Date of Patent: March 3, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Masami Nakane
  • Patent number: 4639461
    Abstract: 7-Oxabicycloheptane substituted keto-amide prostaglandin analogs are provided having the structural formula ##STR1## wherein m is 0 to 4; A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; Q is --CH.dbd.CH--, --CH.sub.2 --, ##STR2## or a single bond; R is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, ##STR3## wherein R.sup.4 and R.sup.5 are the same or different and are H, lower alkyl, hydroxy, lower alkoxy or aryl, at least one of R.sup.4 and R.sup.5 being other than hydroxy and lower alkoxy; p is 1 to 4; R.sup.1 is H or lower alkyl; and R.sup.2 is H, lower alkyl, lower alkenyl, aryl, arylalkyl, cycloalkyl or cycloalkylalkyl.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: October 28, 1985
    Date of Patent: January 27, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Masami Nakane
  • Patent number: 4638012
    Abstract: 7-Oxabicycloheptane .alpha.-substituted ketone prostaglandin analogs are provided having the structural formula ##STR1## wherein m is 0 to 4; A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; X is halogen, alkanoyloxy or hydroxy; p is 1 to 4; R.sup.1 is H or lower alkyl; q is 1 to 12; R.sup.2 is H or lower alkyl; and R.sup.3 is H, lower alkyl, lower alkenyl, lower alkynyl, aryl, arylalkyl, lower alkoxy, aryloxy, amino, alkylamino, or arylamino.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: November 5, 1985
    Date of Patent: January 20, 1987
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Masami Nakane
  • Patent number: 4632931
    Abstract: 7-Oxabicycloheptane substituted amide-sulfonamide prostaglandin analogs are provided having the structural formula ##STR1## wherein m is 0 to 4; A is --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 --; n is 1 to 5; Q is --CH.dbd.CH--, --CH.sub.2 --, ##STR2## or a single bond; R is CO.sub.2 H, CO.sub.2 alkyl, CO.sub.2 alkali metal, CO.sub.2 polyhydroxyamine salt, --CH.sub.2 OH, ##STR3## wherein R.sup.4 and R.sup.5 are the same or different and are H, lower alkyl, hydroxy, lower alkoxy or aryl, at least one of R.sup.4 and R.sup.5 being other than hydroxy and lower alkoxy; p is 1 to 4; R.sup.1 is H or lower alkyl; q is 1 to 12; R.sup.2 is H or lower alkyl; and R.sup.3 is lower alkyl, aryl, arylalkyl, cycloalkyl or cycloalkylalkyl.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: September 25, 1985
    Date of Patent: December 30, 1986
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Masami Nakane
  • Patent number: 4628061
    Abstract: Novel compounds have a formula (I) ##STR1## wherein ##STR2## represents a bicyclo [2,2,1] hept-2Z-ene, bicyclo [2,2,1] heptane, 7-oxa-bicyclo [2,2,1] hept-2Z-ene, 7-oxa-bicyclo [2,2,1] heptane, bicyclo [2,2,2] oct-2Z-ene or bicyclo [2,2,2] octane substituted at the 5-position by the group R.sup.1 and at the 6-position by the group ANR.sup.2 R, a 6,6-dimethyl-bicyclo [3,1,1] heptane substituted at the 2-position by the group R.sup.1 and at the 3-position by the group ANR.sup.2 R or at the 2-position by the group ANR.sup.2 R and at the 3-position by the group R.sup.1, a cyclohex-1-ene or cyclohexane substituted at the 4-position by the group R.sup.1 and at the 5-position by the group ANR.sup.2 R or a 1-hydroxycyclopentane substituted at the 2-position by the group R.sup.1 and at the 2-position by the group ANR.sup.2 R, R.sup.
    Type: Grant
    Filed: August 23, 1983
    Date of Patent: December 9, 1986
    Assignee: National Research Development Corporation
    Inventors: Robert L. Jones, Norman H. Wilson
  • Patent number: 4626548
    Abstract: 7-Oxabicycloheptane substituted prostaglandin alcohols are provided having the structural formula ##STR1## wherein A is --CH.dbd.CH-- or (CH.sub.2).sub.2 ; m is 1 to 5; Q is --CH.dbd.CH-- or (CH.sub.2).sub.2 ; R is H, alkali metal or alkyl; and R.sup.2 is ##STR2## wherein R.sup.3 is H or lower alkyl and R.sup.4 is H or I and including all steroisomers thereof.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: August 19, 1985
    Date of Patent: December 2, 1986
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Steven E. Hall
  • Patent number: 4614825
    Abstract: 7-Oxabicycloheptane and 7-oxabicycloheptene prostaglandin analogs are provided having the structural formula ##STR1## and including all stereoisomers thereof. The compounds are cardiovascular agents useful, for example, in the treatment of thrombolytic disease.
    Type: Grant
    Filed: July 25, 1985
    Date of Patent: September 30, 1986
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: David L. Snitman, Martin F. Haslanger, Peter W. Sprague
  • Patent number: 4610983
    Abstract: This invention relates to a novel N-acyl acidic amino acid diamide derivative represented by the general formula or a salt thereof: ##STR1## wherein each of R.sup.1, R.sup.2, R.sup.3 and R.sup.4, which may be the same or different, represents a hydrogen atom or a substituted or unsubstituted alkyl, cycloalkyl, alkenyl or aralkyl group, or R.sup.1 and R.sup.2 and/or R.sup.3 and R.sup.4, when taken together with the respective adjacent nitrogen atoms, form a substituted or unsubstituted heterocyclic group; R.sup.5 represents a substituted or unsubstituted cycloalkyl, acyl or heterocyclic group; A represents a bond or a substituted or unsubstituted alkylene, alkenylene or alkadienylene group; and n is 1, 2 or 3. Said compound has an anti-ulcer activity which is effective to human beings and animals. This disclosure relates to such a compound, to a process for the production thereof and to an anti-ulcer agent containing the same.
    Type: Grant
    Filed: December 3, 1984
    Date of Patent: September 9, 1986
    Assignee: Toyama Chemical Co., Ltd.
    Inventors: Noboru Takagawa, Shiro Hirai, Takuya Kodama, Hiroshi Hirano, Yasuo Kiba, Mikio Kawabata, Tatsuya Miyaura, Yasuyuki Suzuki
  • Patent number: 4611007
    Abstract: 7-Oxabicycloheptane substituted prostaglandin analogs are provided having the structural formula ##STR1## and including all stereoisomers thereof. The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease and as inhibitors of 5-lipoxygenase enzyme.
    Type: Grant
    Filed: April 22, 1985
    Date of Patent: September 9, 1986
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Jagabandhu Das
  • Patent number: 4608386
    Abstract: 7-Oxabicycloheptane substituted ether prostaglandin analogs are provided having the structural formula ##STR1## wherein X is O or ##STR2## and including all stereoisomers thereof. The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: April 26, 1985
    Date of Patent: August 26, 1986
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Steven E. Hall, Wen-Ching Han
  • Patent number: 4607048
    Abstract: 7-Oxabicycloheptane substituted aryl amino prostaglandin analogs are provided having the structural formula ##STR1## wherein A is --CH.dbd.CH-- or --(CH.sub.2).sub.2 --; m is 1 to 8; n is 1 to 5; R is H, lower alkyl, alkali metal or a polyhydroxyamino salt; R.sup.1 is H, lower alkyl, hydroxyalkyl or aryl; R.sup.2 is H, lower alkyl, aryl or cycloalkyl, R.sup.3 is substituted aryl wherein the aryl group (which may be phenyl or naphthyl) is substituted with one or two of the following groups: hydroxy, ##STR2## SR.sup.4, --CN, --NO.sub.2, ##STR3## wherein R.sup.4 and R.sup.5 may be the same or different and are H or lower alkyl, and including all stereoisomers thereof.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease.
    Type: Grant
    Filed: May 16, 1985
    Date of Patent: August 19, 1986
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Masami Nakane
  • Patent number: 4607049
    Abstract: 7-Oxabicycloheptane substituted thio prostaglandin analogs are provided having the structural formula ##STR1## wherein R is hydrogen, lower alkyl, alkali metal, or a polyhydroxylamine salt, R.sup.1 is hydrogen, lower alkyl, arylalkyl, aryl, cycloalkyl or cycloalkylalkyl, R.sup.2 is hydrogen or lower alkyl, A is --CH.dbd.CH-- or --(CH.sub.2).sub.2, n is 1 to 4, n' is 0, 1 or 2, q is 1 to 10 and m is 0 to 8, and including all stereoisomers thereof.The compounds are cardiovascular agents useful, for example, in the treatment of thrombotic disease, and as such are useful in inhibiting platelet aggregation.
    Type: Grant
    Filed: April 22, 1985
    Date of Patent: August 19, 1986
    Assignee: E. R. Squibb & Sons, Inc.
    Inventor: Steven E. Hall
  • Patent number: 4606753
    Abstract: Novel oxabicycloalkane ether of the formula ##STR1## wherein X is a single bond or --C(CH.sub.3).sub.2 -- and Y is a single bond or --CH.sub.2 -- with the proviso that both X and Y are not a single bond; R is H or --C(O)R.sup.3 in which R.sup.3 is H or certain hydrocarbyl groups; R.sup.1 is certain hydrocarbyl groups, or certain derivatives thereof, such as esters or carbamoyl compounds; and R.sup.2 is cyano or certain unsaturated, aromatic, heterocyclic, cycloalkyl, cycloalkenyl or secondary alkyl group, are useful as herbicides or plant growth regulators.
    Type: Grant
    Filed: June 15, 1984
    Date of Patent: August 19, 1986
    Assignee: Shell Oil Company
    Inventor: James E. Powell
  • Patent number: 4605740
    Abstract: The present invention relates to a process for the production of N-substituted acrylic acid amides by conversion of 2-carboalkoxy-t-oxabicyclo(2,2,1)hept-5-enes with primary or secondary amines to 2-carboxamide-7-oxabicyclo(2,2,1)hept-5-enes and the thermal decomposition of the latter, preferably in the presence of Lewis acids and in a vacuum, to furane and N-substituted acrylic acid amides. The process according to the invention results in high purity N-substituted acrylic acid amides that are, in the main, free of bifunctional monomers which would disrupt the subsequent polymerization of the N-substituted acrylic acid amides by undesired cross-linking.
    Type: Grant
    Filed: September 22, 1983
    Date of Patent: August 12, 1986
    Assignee: Chemische Fabrik Stockhausen GmbH
    Inventor: Alfons Landscheidt
  • Patent number: 4602934
    Abstract: Novel compounds of the formula ##STR1## wherein D is hydrogen, halogen, (halo)alkyl or (halo)alkoxy; R is alkyl or is cycloalkyl optionally 1-substituted by alkyl or halogen and R.sup.1 is the hydrocarbyl residue of a saturated oxygen-heterocyclic alcohol, are useful as herbicides.
    Type: Grant
    Filed: November 13, 1984
    Date of Patent: July 29, 1986
    Assignee: Shell Oil Company
    Inventor: Kurt H. Pilgram