Plural Ring Hetero Atoms In The Tetracyclo Ring System Patents (Class 548/421)
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Patent number: 5843937Abstract: The present invention relates to novel DNA alkylating agents and the prodrugs of these agents which are useful as antitumor agents and DNA labelling agents. The compounds are hydroxy dihydrobenzindole oligopeptides and prodrugs thereof wherein the monomeric constituents are derived from monocyclic or bicyclic heterocyclic aromatic residues.Type: GrantFiled: May 23, 1996Date of Patent: December 1, 1998Assignee: Panorama Research, Inc.Inventors: Yuqiang Wang, Susan C. Wright, James W. Larrick
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Patent number: 5786377Abstract: The pyrrolo?3,2-e! derivatives of the present invention have the formulae (I), (Ia) and (II) wherein R is substituted or unsubstituted aryl or heteroaryl, R' is substituted or unsubstituted alkanoyl, alkenoyl, alkynoyl, arenocarbonyl or heteroarenocarbonyl and X is chloro, bromo, iodo or alkylsulfonyl or arylsulfonyl. The compounds find utility as agents having antitumor activity, and are thus useful agents in the treatment of cancer.Type: GrantFiled: January 29, 1997Date of Patent: July 28, 1998Assignee: Universidad de Santiago de CompostelaInventors: Jose Delamano Garcia, Gabriel Tojo Suarez, Carmen Lopez Goti, Jesus Fernandez Almeida, Dolores Garcia Gravalos, Glynn Thomas Faircloth
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Patent number: 5786486Abstract: Acrylamide derivatives represented by General Formula (1) below: ##STR1## (One specific example of General Formula (1) is methyl (S,S)-3,3'-?3,3'-(1,4-phenylenediacryloyl)!-bis?1-chloromethyl-5-hydroxy-7 -triflouromethyl-1, 2,3,6-tetrahydropyrrolo?3,2-e!indole-8-carboxylate.)The acrylamide derivatives represented by General Formula (1) is highly selective to cancer cells, less toxic, and highly active also against solid tumor.Type: GrantFiled: May 13, 1997Date of Patent: July 28, 1998Assignees: Kyorin Pharmaceutical Co., Ltd., Sagami Chemical Research CenterInventors: Yasumichi Fukuda, Shigeki Seto, Yasuo Oomori, Hiroyuki Ebisu, Shiro Terashima
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Patent number: 5754271Abstract: The invention relates to photochromic compounds of general formula: ##STR1## wherein R.sup.a, R.sup.b and R.sup.c is denote hydrogen; alkyl; aryl; OR, SR, COR or COOR, in which R denotes hydrogen, alkyl or aryl, amino of formula NR.sub.1 R.sub.2 in which R.sub.1 and R.sub.2 denote hydrogen, alkyl, cycloalkyl or an aryl; a halogen atom; a mono- or polyhaloalkyl group; or an NO.sub.2, CN or SCN group; n and m denote integers from 1 to 5; p is equal to 1 or 2; and H is a 5-members aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen and sulfur, these heterocyclic nuclei being eventually substituted by one or more alkyl, alkoxy, amino, aryl or aralkyl groups or condensed with a phenyl nucleus, a substituted phenyl nucleus or a 6-members cycloaliphatic nucleus and to their use in ophtalmic optics.Type: GrantFiled: June 3, 1996Date of Patent: May 19, 1998Assignee: Essilor International (Compagnie General d'Optique)Inventors: Robert Guglielmetti, Jean Luc Pozzo, Andre Samat
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Patent number: 5747520Abstract: Azatoxin and derivatives thereof are illustrative of a new class of antitumor drugs that are topoisomerase II (top 2) inhibitors. The pharmacophore inhibits the catalytic activity of the purified enzyme but does not unwind relaxed or supercoiled DNA. It is nonintercalative and has at least two domains: a quasi-planar polycyclic ring system, which may bind between DNA base pairs, and a pendant substituent thought to interact with the enzyme, with the DNA grooves or with both. In SV40 and c-myc DNA, azatoxin induces numerous double-strand breaks according to a cleavage pattern which differs from those of known top 2 inhibitors. Azatoxin also is a potent inhibitor of tubulin polymerization.Type: GrantFiled: June 2, 1995Date of Patent: May 5, 1998Inventors: Yves Pommier, Timothy Lee MacDonald, Jose S. Madalengoitia
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Patent number: 5739350Abstract: This invention provides some new synthetically obtained compounds of formula I and II ##STR1## which are useful as chemical intermediates. Representative formula I or II compounds have also been shown to possess useful ranges of antitumor activity in standard laboratory animal tests.In addition, the compounds of formula I or II can be linked to monoclonal antibodies, either directly or via known linking group, as a means of selectively delivering the CC-1065 analogs (Compounds of Formula I and II) to those target cells expressing the target antigen and thus selectively eliminating those diseased cells from the animal or human. Further, the compounds of formula I and II can be linked to soluble human CD4 or a soluble human CD4 protein fragment capable of binding to the gp120 envelope protein of the human immuno-virus and thus eliminate virally infected cells.Type: GrantFiled: June 7, 1995Date of Patent: April 14, 1998Assignee: Pharmacia & Upjohn CompanyInventors: Robert C. Kelly, Mark A. Mitchell, Paul A. Aristoff
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Patent number: 5726186Abstract: The present invention provides compounds of formula I: ##STR1## wherein X is --O-- or --S--,Y is --O--, --S--, --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, or --NR.sup.5 --;R.sup.1, R.sup.2, and R.sup.3 are each independently --H, --OH, --O(C.sub.1 -C.sub.4 alkyl), --OCOC.sub.6 H.sub.5, --OCO(C.sub.1 -C.sub.6 alkyl), --OSO.sub.2 (C.sub.4 -C.sub.6 alkyl), --OSO.sub.2 CF.sub.3, Cl, or F;n is 1 or 2;W is CH.sub.2 or C.dbd.O;R.sup.4 is 1-piperidinyl, 2-oxo-1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 2-oxo-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino;R.sup.5 is C.sub.1 -C.sub.3 alkyl, --COC.sub.6 H.sub.5, --CO(C.sub.1 -C.sub.6 alkyl), --C(O)OC.sub.6 H.sub.5, --C(O)O(C.sub.1 -C.sub.6 alkyl), --SO.sub.2 (C.sub.1 -C.sub.6 alkyl), --SO.sub.2 C.sub.6 H.sub.5, or --SO.sub.2 CF.sub.3 ;or a pharmaceutically acceptable salt or solvate thereof.Type: GrantFiled: August 13, 1996Date of Patent: March 10, 1998Assignee: Eli Lilly and CompanyInventor: Timothy Alan Grese
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Patent number: 5723484Abstract: Compounds of formula (I): ##STR1## in which: n represents 1 or 2,R.sub.1 represents hydrogen or alkyl, benzyl, acetyl, benzoyl, allyl, pyridinecarbonyl, pyridinemethyl, acylaminoalkyl (optionally substituted), pyridineaminocarbonyl, phthalimidoalkyl, thiochromanyloxyalkyl or (benzodioxanyloxy)alkyl,R.sub.2, R.sub.3 or R.sub.4, which may be identical or different, represent hydrogen or halogen or alkyl, alkoxy, hydroxyl, acetyl, aminocarbonyl, aminomethyl, cyano, nitro, amino, phenyl (which may or may not be substituted), furyl, pyridinyl, thienyl or pyridyl, or alternatively, when they are located on adjacent carbons, R.sub.2 and R.sub.3 form, with the carbon atoms which bear them, a furan or phenyl ring,the isomers thereof and the addition salts thereof with a pharmaceutically acceptable acid, and medicinal products containing the same are useful for the treatment of diseases requiring a ligand to the 5-HT.sub.2C receptors.Type: GrantFiled: January 21, 1997Date of Patent: March 3, 1998Assignee: Adir et CompagnieInventors: Gilbert Lavielle, Thierry Dubuffet, Mark Millan, Adrian Newman-Tancredi
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Patent number: 5679694Abstract: The invention relates to compounds of formula (I) which have been found to possess anti-tumor activity. Pharmaceutical compositions and methods of treating tumors are also disclosed.Type: GrantFiled: November 4, 1996Date of Patent: October 21, 1997Assignees: The Wellcome Foundation Ltd., University College Cardiff Consultants LimitedInventors: Karl Witold Franzmann, Jeremy Nigel Stables, Patrick Vivian Richard Shannon, Nagaraja Kodanda Ranganatha Rao, Laddawan Chunchatprasert
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Patent number: 5674432Abstract: Described are novel reversible photochromic diaryl-3H-naphtho?2,1-b!pyran compounds having a substituted or unsubstituted, five or six member heterocyclic ring fused to the g, i, or l side of the naphthopyran. The heterocyclic ring contains an oxygen or nitrogen atom and is attached to the number 5, 6, 7, 8, 9, or 10 carbon atom of the naphtho portion of the naphthopyran. Also described are organic host materials containing such compounds. Articles such as ophthalmic lenses or other plastic transparencies that incorporate the novel naphthopyran compounds or combinations thereof with complementary photochromic compounds, e.g., spiro(indoline)oxazine-type compounds, are also described.Type: GrantFiled: June 2, 1995Date of Patent: October 7, 1997Assignee: Transitions Optical, Inc.Inventors: David B. Knowles, Barry Van Gemert
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Patent number: 5670492Abstract: Provided are DC-89 derivatives represented by the formula: ##STR1## wherein X represents Cl or Br, R represents hydrogen or COR.sup.1, and W represents ##STR2## and pharmaceutically acceptable salts thereof. The compounds of the present invention have excellent anti-tumor activity and are useful as anti-tumor agents.Type: GrantFiled: November 28, 1995Date of Patent: September 23, 1997Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Nobuyoshi Amishiro, Satoru Nagamura, Hiromitsu Saito, Eiji Kobayashi, Akihiko Okamoto, Katsushige Gomi
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Patent number: 5629430Abstract: Trifluoromethylpyrroloindolecarboxylic acid ester derivatives, and optical isomers and pharmaceutically acceptable salts thereof are provided which are represented by the general formula (1): ##STR1## or the general formula (2): ##STR2## The compounds are antineoplastic agents which are selective to cancer cells, effective also to solid cancer, and less toxic.Type: GrantFiled: June 14, 1995Date of Patent: May 13, 1997Assignees: Kyorin Pharmaceutical Co., Ltd., Sagami Chemical Research CenterInventors: Shiro Terashima, Yasumichi Fukuda, Yasuo Oomori
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Patent number: 5541339Abstract: This invention concerns chemical compounds of general Formula ICPI.sub.1 -R.sub.5 -T-R'.sub.5 -CPI.sub.2 IThe compounds of Formula I are useful as uv light absorbers, antibacterial agents, and are particularly useful as antitumor agents. Representative compounds of Formula I have been shown to possess useful ranges of antitumor activity in standard laboratory animal tests.Type: GrantFiled: March 8, 1991Date of Patent: July 30, 1996Assignee: The Upjohn CompanyInventors: Robert C. Kelly, Paul A. Aristoff
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Patent number: 5523411Abstract: The present invention relates to the synthesis of mitomycin and analogs thereof that are useful as anticancer antibiotics. The invention further relates to analogs of mitomycin, which can be prepared according to the methods of synthesis provided. The synthetic method of the invention provides for reacting a derivitized indole with a dialkylvinylsulfonium salt to yield a tricyclic skeleton having the precursors of the fourth ring in one step, followed by an oxidation step or steps to close the fourth ring and prepare mitomycin or a related compound.Type: GrantFiled: March 14, 1994Date of Patent: June 4, 1996Assignee: Rutgers UniversityInventors: Leslie Jimenez, Zheng Wang
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Patent number: 5502068Abstract: The invention is directed to novel cyclopropylpyrroloindole-oligopeptide compounds which are useful as anticancer agents. The novel cyclopropylpyrroloindole-oligopeptide compounds have the following general structure: ##STR1## wherein, Het.sup.1 and Het.sup.2 are individually selected from the group consisting of pyrrole, imidazole, triazole, thiophene, furan, thiazole, oxazole and pyrazole,R is selected from the group consisting of a valence bond; a C.sub.1 -C.sub.6 alkyl; a C.sub.2 -C.sub.6 alkenyl; a C.sub.2 -C.sub.6 alkynyl; and an ortho, meta or para linked aromatic group,A is selected from the group consisting of a C.sub.1 -C.sub.6 alkyl group; an amidine or derivative thereof; a guanidine; a secondary, tertiary or quaternary ammonium salt; and a sulfonium salt,n is 0 to 3, andm is 0 to 3.Type: GrantFiled: January 31, 1995Date of Patent: March 26, 1996Assignee: Synphar Laboratories, Inc.Inventors: J. William Lown, Yuqiang Wang, Weide Luo
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Patent number: 5486611Abstract: This invention is therapeutically useful tetralins and pharmaceutically acceptable acid addition salts thereof of the formula I: ##STR1## wherein X is --(CH.sub.2).sub.n -- or --C(R.sub.1)(H)--; R is C.sub.1 -C.sub.8 alkyl; and R.sub.1 and R.sub.2 are the same or different and are selected from the group consisting of hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8) alkynyl, aryl and benzyl.These compounds are useful to treat central nervous system disorders and are unexpectedly resistant to metabolism by the liver and have superior oral plasma bioavailability.Type: GrantFiled: October 28, 1993Date of Patent: January 23, 1996Assignee: The Upjohn CompanyInventors: Chiu-Hong Lin, Susanne R. Haadsma-Svensson, Robert B. McCall, Arthur G. Romero, William H. Darlington, Michael D. Ennis
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Patent number: 5451344Abstract: Described are novel reversible photochromic diaryl-3H-naphtho[2,1-b]pyran compounds having a substituted or unsubstituted, five or six member heterocyclic ring fused to the g, i, or l side of the naphthopyran. The heterocyclic ring contains an oxygen or nitrogen atom and is attached to the number 5, 6, 7, 8, 9, or 10 carbon atom of the naphtho portion of the naphthopyran. Also described are organic host materials containing such compounds. Articles such as ophthalmic lenses or other plastic transparencies that incorporate the novel naphthopyran compounds or combinations thereof with complementary photochromic compounds, e.g., spiro(indoline)oxazine-type compounds, are also described.Type: GrantFiled: April 8, 1994Date of Patent: September 19, 1995Assignee: Transitions Optical, Inc.Inventors: David B. Knowles, Barry Van Gemert
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Patent number: 5442066Abstract: Novel bleach catalysts, a method for bleaching substrates using these catalysts and detergent compositions containing same are reported. The bleaches are of the quaternary oxaziridinium salt type. Substrates such as fabrics may be bleached in an aqueous solution containing the quaternary oxaziridinium salt.Type: GrantFiled: September 2, 1994Date of Patent: August 15, 1995Assignee: Lever Brothers Company, Division of Conopco, Inc.Inventors: Stephen A. Madison, Janet L. Coope
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Patent number: 5332837Abstract: This invention concerns 2-acyl-4,5,8,8a-tetrahydro-4-oxycyclopropan[c]pyrrol(3,2-e) indole derivatives of Formula I': ##STR1## the compounds of Formula I' are useful as uv light absorber substances, as chemical intermediates and as prodrugs of known spirocyclopropylpyrroloindole CC-1065 analogs. Representative Formula I' compounds have been shown to possess useful ranges of antitumor activity in standard laboratory animal tests.Type: GrantFiled: January 22, 1993Date of Patent: July 26, 1994Assignee: The Upjohn CompanyInventors: Robert C. Kelly, David G. Martin, Paul A. Aristoff
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Patent number: 5319095Abstract: This invention provides a process for preparing kainic acid and provides intermediates in the synthesis thereof.Type: GrantFiled: December 4, 1992Date of Patent: June 7, 1994Assignee: Eli Lilly and CompanyInventor: James A. Monn
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Patent number: 5276053Abstract: A novel series of polycyclic amines, derivatives, methods of making the compounds, novel intermediates, compositions containing them, and methods for using them in the treatment and prevention of cerebrovascular disorders are disclosed.Type: GrantFiled: October 6, 1992Date of Patent: January 4, 1994Assignee: Warner-Lambert CompanyInventor: Graham Johnson
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Patent number: 5274114Abstract: This invention relates to the preparation of 3- and/or 4-substituted pyrrolidine catalysts corresponding to formula (I) ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, X.sub.1, X.sub.2, and Y have the meanings described for formula (I) and to use of such catalysts in the polyisocyanate polyaddition process.Type: GrantFiled: February 10, 1992Date of Patent: December 28, 1993Assignee: Bayer AktiengesellschaftInventors: Richard Weider, Uwe Scholz, Andreas Ruckes
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Patent number: 5258383Abstract: DC-89 derivatives represented by the formula: ##STR1## wherein X represents hydrogen or CO.sub.2 CH.sub.3 ; and ##STR2## wherein Z represents Cl or Br; R represents hydrogen, CONR.sup.1 R.sup.2 (in which R.sup.1 and R.sup.2 independently represent hydrogen, a straight-chain or branched alkyl group having 1 to 4 carbon atoms or phenyl) or ##STR3## (in which n represents an integer of 0 to 4; R.sup.3 represents CH.sub.2, ##STR4## oxygen, N--CH.sub.3, or N--CH.sub.2 CONR.sup.1 R.sup.2 in which R.sup.1 and R.sup.2 have the same significances as defined above); and W represents hydrogen or ##STR5## (in which W.sup.1 and W.sup.2 independently represent hydrogen or OR.sup.2 in which R.sup.Type: GrantFiled: June 25, 1992Date of Patent: November 2, 1993Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Satoru Nagamura, Hiromitsu Saito, Eiji Kobayashi, Katsushige Gomi
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Patent number: 5229410Abstract: The present invention provides 4-amino-6-substituted-hexahydrobenz[cd]indoles which are useful in treating disease states which can be benefited by an alteration of 5-HT.sub.1A receptors.Type: GrantFiled: July 3, 1991Date of Patent: July 20, 1993Assignee: Eli Lilly and CompanyInventors: Michael E. Flaugh, Michael J. Martinelli, John M. Schaus
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Patent number: 5229409Abstract: The present invention involves certain 4-amino-6-substituted-tetrahydrobenz[cd]indoles and their use in treating disorders which can be benefited by modifying 5-HT A receptor function.Type: GrantFiled: July 3, 1991Date of Patent: July 20, 1993Assignee: Eli Lilly and CompanyInventors: Michael E. Flaugh, Michael J. Martinelli, John M. Schaus
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Patent number: 5221681Abstract: The present invention relates to new substituted benzoxazepines and benzothiazepines of the general formula I ##STR1## in which X, R.sup.1, R.sup.2 and R.sup.3 have the meaning given in the description, processes for their preparation and their use in medicaments having vaso- and muscle-relaxing properties, in particular as circulatory agents.Type: GrantFiled: January 16, 1992Date of Patent: June 22, 1993Assignee: Bayer AktiengesellschaftInventors: Hans-Joachim Kabbe, Helmut Heitzer, Andreas Knorr, Claudia Hirth-Dietrich
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Patent number: 5187186Abstract: DC-88A derivatives represented by the general formula: ##STR1## wherein X represents hydrogen or CO.sub.2 R.sup.1 (in which R.sup.1 represents hydrogen, a straight-chain or branched alkyl having 1 to 4 carbon atoms, allyl, or benzyl); and ##STR2## have an excellent anti-tumor activity and are useful as anti-tumor agents.Type: GrantFiled: September 6, 1991Date of Patent: February 16, 1993Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Yutaka Kanda, Youichi Uosaki, Hiromitsu Saito, Hiroshi Sano, Eiji Kobayashi, Makoto Morimoto, Satoru Nagamura
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Patent number: 5180736Abstract: A novel series of polycyclic amines, derivatives, methods of making the compounds, novel intermediates, compositions containing them, and methods for using them in the treatment and prevention of cerebrovascular disorders are disclosed.Type: GrantFiled: May 17, 1991Date of Patent: January 19, 1993Assignee: Warner-Lambert CompanyInventor: Graham Johnson
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Patent number: 5180733Abstract: Compounds of the formula: ##STR1## or a pharmaceutically acceptable salt thereof, wherein M is 0, 1 or 2 and n is 0 or 1;R.sup.1 is hydrogen or lower alkyl;R.sup.2 is C.sub.1 -C.sub.6 -alkyl substituted with a heterocyclic group or C.sub.7 -C.sub.16 -arylalkyl, wherein the aryl group is unsubstituted or substituted with from one to three non-hydrogen members independently selected from the group consisting of halogen, C.sub.1 -C.sub.6 -alkyl, halo-C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkoxy, hydroxy, amino and C.sub.1 -C.sub.6 -alkylamino;R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are independently selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 -alkoxy, C.sub.1 -C.sub.6 -alkyl, halogen, and halo-C.sub.1 -C.sub.6 -alkyl, or any two of R.sup.3, R.sup.4, R.sup.5 and R.sup.6 taken together form a methylenedioxy group; andR.sup.7 is hydrogen or C.sub.1 -C.sub.6 -alkyl.Type: GrantFiled: March 22, 1991Date of Patent: January 19, 1993Assignee: Abbott LaboratoriesInventors: Fatima Z. Basha, John F. DeBernardis, Robert J. Altenbach
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Patent number: 5126363Abstract: Indole derivatives of formula (I) ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may be hydrogen or lower alkyl optionally substituted by halogen; A.sup.1 represents a straight or branched alkylene chain containing from 2 to 4 carbon atoms; R.sup.5 is hydrogen or a straight or branched alkyl group; A.sup.2 is a straight or branched, saturated or unsaturated hydrocarbon chain containing from 2 to 6 carbon atoms; and R.sup.6 is selected from a group consisting of various structures, have been found to exhibit central nervous system activities.Type: GrantFiled: January 23, 1991Date of Patent: June 30, 1992Assignee: Novo Nordisk A/SInventors: Lone Jeppesen, Peter H. Andersen, Louis B. Hansen, Peter Faarup, John B. Hansen
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Patent number: 5117006Abstract: A DC-88A derivative represented by general formula: ##STR1## wherein ##STR2## represents ##STR3## has an excellent antitumor activity and is useful as an anti-tumor agent.Type: GrantFiled: May 15, 1991Date of Patent: May 26, 1992Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Hiromitsu Saito, Masaji Kasai, Makoto Morimoto, Eiji Kobayashi, Yoichi Uosaki, Yutaka Kanda, Hiroshi Sano
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Patent number: 5102905Abstract: The invention concerns heterocyclic nitromethane derivatives of the formula 1 as defined hereinafter (and their non-toxic salts) wherein the heterocyclic moiety Q is thienyl, benzothienyl or dibenzothienyl and may bear a wide variety of optional substituents, together with pharmaceutical compositions containing them. The nitromethane derivatives are inhibitors of the enzyme aldose reductase and are of value in the treatment of certain complications of diabetes and galactosemia.Type: GrantFiled: April 28, 1989Date of Patent: April 7, 1992Assignee: Imperial Chemical Industries PLCInventors: Steven P. Brown, Anthony L. Cooper, Jethro L. Longridge, Jeffrey Morris, John Preston
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Patent number: 5101038Abstract: A novel fermentation product, DC113, represented by the formula ##STR1## which has antimicrobial and antitumor activities.Type: GrantFiled: December 28, 1989Date of Patent: March 31, 1992Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Hirofumi Nakano, Isami Takahashi, Isao Kawamoto, Toru Yasuzawa, Keiichi Takahashi, Eiji Kobayashi
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Patent number: 5071853Abstract: A novel series of polycyclic amines, derivatives, methods of making the compounds, novel intermediates, compositions containing them, and methods for using them in the treatment and prevention of cerebrovascular disorders are disclosed.Type: GrantFiled: February 27, 1990Date of Patent: December 10, 1991Inventors: Christopher F. Bigge, Sheryl J. Hays, Graham Johnson, Perry M. Novak, Daniel F. Ortwine
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Patent number: 5070092Abstract: DC-88A derivatives represented by the general formula: ##STR1## wherein X represents hydrogen or CO.sub.2 R.sup.1 (in which R.sup.1 represents hydrogen, a straight-chain or branched alkyl having 1 to 4 carbon atoms, allyl, or benzyl); and ##STR2## have an excellent anti-tumor activity and are useful as anti-tumor agents.Type: GrantFiled: June 29, 1990Date of Patent: December 3, 1991Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Yutaka Kanda, Youichi Uosaki, Hiromitsu Saito, Hiroshi Sano, Eiji Kobayashi, Makoto Morimoto, Satoru Nagamura
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Patent number: 5064831Abstract: Naphthothiophenimines of formula I ##STR1## wherein R.sup.1 is, inter alia, alkyl, cycloaklyl, alkenyl, phenalkyl or aminoalkyl.Formula I compounds are useful in treating brain ischemia and resulting disorders.Type: GrantFiled: September 14, 1990Date of Patent: November 12, 1991Assignee: Bristol-Myers Squibb Co.Inventor: Katherine S. Takaki
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Patent number: 4999369Abstract: The present invention relates to compounds of formula (I)ArCH.sub.2 R.sup.1 (I)or a monomethyl or monoethyl ether thereof (the compound of formula (I) including these ethers may contain no more than 29 carbon atoms in total); ethers, esters thereof; acid addition salts thereof; wherein Ar is a fused tetracyclic aromatic ring system comprised of 5-membered and 6-membered rings and contains at least one heteroatom and 3 aromatic rings and a total of no more than 18 ring atoms, or a substituted derivative thereof; the heteroatom is preferably oxygen, sulfur or nitrogen; when it is nitrogen this is substituted by hydrogen, methyl or ethyl;R.sup.1 contains not more than eight carbon atoms and is a group ##STR1## wherein m is 0 or 1; R.sup.5 is hydrogen;R.sup.6 and R.sup.7 are the same or different and each is hydrogen or C.sub.1-5 alkyl optionally substituted by hydroxy;R.sup.8 and R.sup.9 are the same or different and each is hydrogen or C.sub.Type: GrantFiled: February 15, 1990Date of Patent: March 12, 1991Assignee: Burroughs Wellcome Co.Inventor: Kenneth W. Bair
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Patent number: 4996223Abstract: New echiboline derivatives with opioid properties which are 6-hydroxy-9-methyl-echiboline derivatives having, in the 10-position, a hydrocarbon substituent of up to 4 carbon atoms--preferably a group R.CH.sub.2 -- (wherein R represents a hydrogen atom or a hydrocarbon group of up to 3 carbons) and especially a methyl, cyclopropyl-methyl or allyl group.These are made by dealkylating corresponding 6-alkoxy-9-methyl-10-substituted echibolines, thereby converting the 6-alkoxy group to a 6-hydroxy group, especially using boron tribromide as dealkylating reagent.Specific examples are 6-hydroxy-9,10-dimethyl-echiboline, 6-hydroxy-9-methyl-10-allyl-echiboline and 6-hydroxy-9-methyl-10-cyclopropylmethyl-echiboline.The compounds may be in free base or salt form, and be incorporated as active ingredient into pharmaceutical compositions.Type: GrantFiled: February 9, 1989Date of Patent: February 26, 1991Assignee: The Victoria University of ManchesterInventors: John M. H. Rees, Brian Robinson, Brian Cox
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Patent number: 4978757Abstract: 1,2,8,8a-Tetrahydrocyclopropa[3]pyrrolo(3,2-e)indol-4(5H)-ones, and related compounds of formulas I and intermediate therefor II ##STR1## wherein R.sub.2, R.sub.2 ', R.sub.3, R.sub.5, R.sub.50 and X are as defined in the specification, e.g., (7bR,8aS)-1,2,8,8a -tetrahydro-7-methyl-2-[[5-(((1H-indol-2-yl)carbonyl)amino)-1H-indol-2-yl] carbonyl]cyclopropa[pyrrolo[3,2-e]indol-4(5H)-one (U-71,184), as purified, and its racemic form (U-68,415), and related compounds, are useful as ultraviolet light absorbers and as antibacterials. The lead compounds are useful as antitumor drug compounds in standard laboratory animal tests.Type: GrantFiled: November 30, 1989Date of Patent: December 18, 1990Assignee: The Upjohn CompanyInventors: Robert C. Kelly, Martha A. Warpehoski, Wendell Wierenga
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Patent number: 4977158Abstract: The invention relates to novel tetracyclic compounds with an anti-depressant action, without neuroleptic or sedative side effects, of the general formula I ##STR1## and also functional derivatives hereof, wherein: R.sup.1 represents one or two identical or different substituents denoting H, OH, halogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;R.sup.2 represents one or two identical or different substituents having the same meaning as R.sup.1 ;R.sup.3 and R.sup.4 are two substituents which are in the cis configuration and of which one is H and the other is OH;R.sup.5 is H or C.sub.1 -C.sub.4 alkyl;X denotes O or S;n is 0 or 1.Type: GrantFiled: August 23, 1989Date of Patent: December 11, 1990Assignee: Akzo N.V.Inventor: Johannes H. Wieringa
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Patent number: 4973694Abstract: A 6-tertiary amino-2-(Z.dbd.CH--)benzofuran dye is disclosed, where Z represents the atoms providing an electron withdrawing group and a conjugated methine linkage completing a resonant dye chromophore including the 6-tertiary amino group as an electron donor and the electron withdrawing group as an electron acceptor. The dyes are formed by condensing a 6-tertiary amino-2-formylbenzofuran with an electron withdrawing dye nucleus precursor containing an active methyl or methylene site. The dyes exhibit bathocromically shifted absorption peaks.Type: GrantFiled: August 17, 1989Date of Patent: November 27, 1990Assignee: Eastman Kodak CompanyInventors: Chin H. Chen, John L. Fox
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Patent number: 4923990Abstract: The present invention relates to DC-88A and DC-89A1 and their production. These compounds are obtained by fermentation of microorganisms belonging to the genus Streptomyces. These compounds have antibacterial and anti-tumor activities and are useful as medicaments.Type: GrantFiled: September 9, 1988Date of Patent: May 8, 1990Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Hirofumi Nakano, Isami Takahashi, Michio Ichimura, Isao Kawamoto, Kozo Asasno, Fusao Tomita, Hiroshi Sano, Toru Yasuzawa, Makoto Morimoto, Kazuhisa Fujimoto
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Patent number: 4912107Abstract: The invention concerns new pyrrolocarbazole derivatives of formula ##STR1## processes for their preparation, as well as medicaments containing these for the inhibition of protein kinases, such as protein kinase C, and thus for the prevention and/or treatment of heart and blood vessel diseases, such as thromboses, arterioscleroses, hypertension, of inflammatory processes, allergies, cancers, and certain degenerative damages of the central nervous system as well as for the treatment of viral diseases.Type: GrantFiled: September 26, 1989Date of Patent: March 27, 1990Assignee: Goedecke AktiengesellschaftInventors: Jurgen Kleinschroth, Johannes Hartenstein, Christoph Schachtele, Claus Rudolph, David J. Dooley, Gunther Weinheimer
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Patent number: 4912227Abstract: 1,2,8,8a-Tetrahydrocyclopropa[3]pyrrolo(3,2-e)indol-4(5H)-ones, and related compounds of formulas I and intermediate therefor II ##STR1## wherein R.sub.2, R.sub.2 ', R.sub.3, R.sub.5, R.sub.50 and X are as defined in the specification, e.g., (7bR,8aS)-1,2,8,8a-tetrahydro-7-methyl-2-[[5-(((1H-indol-2-yl)carbonyl)ami no)-1H-indol-2-yl]carbonyl]cyclopropa[pyrrolo[3,2-e]indol-4(5H)-one (U-71,184), as purified, and its racemic form (U-68,415), and related compounds, are useful as ultraviolet light absorbers and as antibacterials. The lead compounds are useful as antitumor drug compounds in standard laboratory animal tests.Type: GrantFiled: August 7, 1986Date of Patent: March 27, 1990Assignee: The Upjohn CompanyInventors: Robert C. Kelly, Martha A. Warpehoski, Wendell Wierenga
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Patent number: 4910314Abstract: There is provided a fluorescent adduct which is amenable to detection by fluorometric and electrochemical techniques. The adduct is of the formula: ##STR1## wherein X is a radical derived from a primary amine of the formula X--NH.sub.2 and where R.sub.1 --R.sub.6 are selected from various organic or inorganic substituents.Type: GrantFiled: January 26, 1989Date of Patent: March 20, 1990Assignee: Oread Laboratories, Inc.Inventors: Pierre M. R. de Montigny, Larry A. Sternson, Arnold J. Repta, John F. Stabaugh, Takeru Higuchi, deceased, by Martin B. Dickinson, Jr., co-executor, by Kenji W. Higuchi, co-executor
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Patent number: 4889937Abstract: Disclosed are new indole derivatives of the following general formula (I): ##STR1## and a process for producing the derivatives (I) by irradiating a solution of a triazolylnaphthalene derivative of the following general formula (II) in a solvent with light: ##STR2## wherein R' represents a hydrogen atom, a halogen atom, an alkyl group, a nitro group or a ##STR3## groups, n represents a number of 1 to 2, and when n is 2, two R groups may be either the same or different from each other and R.sub.n is the same as R'.sub.n or represents a ##STR4## group ortho-condensed with the naphthalene ring: W and Z each represent a hydrogen atom, a halogen atom, an alkyl group, a carboxyl group or an ester group thereof, n represents a number of 1 or 2, and when n is 2, two W groups and two Z groups may be either the same or different from each other, respectively.Type: GrantFiled: August 29, 1988Date of Patent: December 26, 1989Assignee: Agency of Industrial Science and TechnologyInventors: Yoshinobu Nagawa, Koichi Honda, Hiroshi Nakanishi
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Patent number: 4868199Abstract: The present invention relates to novel enolamide type compounds, pharmaceutical compositions, and methods of use thereof, useful in the treatment of diseases in which products of lipoxygenase enzyme activity or the action of leukotrienes contribute to the pathological condition.Type: GrantFiled: March 9, 1988Date of Patent: September 19, 1989Assignee: Warner-Lambert CompanyInventors: Mary E. Carethers, Wiaczeslaw A. Cetenko, David T. Connor, Elizabeth A. Johnson, John S. Kiely, Charles F. Schwender, Jagadish C. Sircar, Roderick J. Sorenson, Paul C. Unangst, Robert F. Bruns
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Patent number: 4861793Abstract: Pharmaceutical compounds of the formula ##STR1## wherein R is H or CH.sub.3, R.sub.1 is H or OCH.sub.3, R.sub.2 is a C.sub.1 -C.sub.4 hydrocarbon group and X is an organic group. Also disclosed is a process for the preparation of these compounds. The compounds have dopamine agonist or antagonist activity.Type: GrantFiled: March 31, 1987Date of Patent: August 29, 1989Assignee: Farmitalia Carlo Erba, S.p.AInventors: Luigi Bernardi, Laura Chiodini, Aldemio Temperilli
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Patent number: 4841045Abstract: A new process for the stereospecific synthesis of alkaloids of the vinblastine and vincristine type including the synthesis of vinblastine and vincristine as well novel alkaloids which are active as anti-tumor agents.Type: GrantFiled: May 18, 1987Date of Patent: June 20, 1989Assignee: University of Vermont & State Agricultural CollegeInventor: Martin Kuehne
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Patent number: 4801588Abstract: Compounds of the formula I: ##STR1## wherein R.sub.1 =H, CH.sub.3 ; m=0,1; R.sub.2 =R.sub.3 =H or R.sub.2, R.sub.3 =bond, R.sub.4 =C.sub.1 -C.sub.4 hydrocarbon, n=1 or 2 and their pharmaceutically acceptable salts are antihypertensive agents. Their preparation and pharmaceutical compositions containing them are also described.Type: GrantFiled: July 15, 1987Date of Patent: January 31, 1989Assignee: Farmitalia Carlo Erba S.p.A.Inventors: Aldemio Temperilli, Rosanna Eccel, Enzo Brambilla, Patricia Salvati