Having -c(=x)-, Wherein X Is Chalcogen Attached Directly Or Indirectly To The Purine Ring System By Nonionic Bonding Or Halogen Bonded Directly At 8-position (e.g., Theophylline Acetate, 8-chlorotheophylline, Etc.) Patents (Class 544/271)
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Patent number: 6075143Abstract: There are described N-ethylglycine derivatives of the formula I ##STR1## in which PG is a urethane-type or trityl-type amino protective group which is labile to weak acids, X is NH, O or S, Y is CH.sub.2, NH or O, and B' are bases customary in nucleotide chemistry, the exocyclic amino or hydroxyl groups of which being protected by suitable, known protective groups, or are base substitute compounds, and their salts with tert-organic bases, as well as a process for their preparation. The N-ethylglycine derivatives of the formula I are used in the preparation of PNA and PNA/DNA hybrids.Type: GrantFiled: March 13, 1995Date of Patent: June 13, 2000Assignee: Hoechst AktiengesellschaftInventors: Gerhard Breipohl, Eugen Uhlmann, Jochen Knolle
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Patent number: 6075029Abstract: A new class of xanthine compounds, variously substituted at the 1, 3, 7 and 8 positions, is characterized by an ability to modulate the activity of key enzymes involved in drug metabolism. These compounds generally are useful in affecting drug metabolism and, particularly, in extending the circulating half-life of compounds that are metabolized via P-450-mediated pathways.Type: GrantFiled: January 2, 1998Date of Patent: June 13, 2000Assignee: Cell Therapeutics, Inc.Inventors: J. Peter Klein, Anil M. Kumar, Paul Woodson
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Patent number: 6066641Abstract: The present invention relates to novel compounds of the formula (I): ##STR1## wherein Q.sub.3 R.sub.3 and Q.sub.8 R.sub.8 are described herein. The compounds possess PDE-IV inhibitory activity and improved selectivity with regard to PDE-III inhibition. Also disclosed are pharmaceutical compositions and methods of treatment utilizing the disclosed compounds.Type: GrantFiled: June 11, 1997Date of Patent: May 23, 2000Assignee: Euro-Celtique S.A.Inventors: David Cavalla, Peter Hofer, Mark Chasin
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Patent number: 6037470Abstract: The present invention comprises a method of synthesizing compounds of formula (I): wherein Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.8 are as described herein; comprising the steps of.Type: GrantFiled: December 10, 1998Date of Patent: March 14, 2000Assignee: Euro-Celtique S.A.Inventors: David J. Cavalla, Mark Chasin, Peter Hofer
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Patent number: 6025361Abstract: Disclosed are compounds of formula (I), wherein R.sup.1, R.sup.3 and R.sup.8 are independently alkyl, aryl or aralkyl, and R.sup.2 is selected from the group consisting of S and O, R.sup.6 is selected from the group consisting of S and O, provided that R.sup.2 and R.sup.6 are not both O. The compounds are effective PDE IV inhibitors and possess improved PDE IV inhibition and improved selectivity with regard to PDE III inhibition. Methods of treatment using the compounds are also disclosed.Type: GrantFiled: September 29, 1997Date of Patent: February 15, 2000Assignee: Euro-Celtique, S.A.Inventors: David Cavalla, Peter Hofer, Mark Chasin
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Patent number: 5994361Abstract: The present invention comprises a compound of formula I: ##STR1## R.sub.1 of Formula I is substituted amino represented by formula NR.sup.5 R.sup.6 wherein R.sup.5 and R.sup.6 are independently selected from the group consisting of hydrogen, C.sub.1-4 alkyl, and unsubstituted amino with the proviso that R.sup.5 and R.sup.6 are not both hydrogen, and further that R.sup.5 and R.sup.6 are not both amino. R.sub.2 and R.sub.3 of Formula I are independently selected from the group consisting of hydrogen; C.sub.1-4 alkyl; amino; substituted or unsubstituted thiol; and halogen. Moreover, R.sub.4 of Formula I is represented by the formula R.sup.12 -X.sup.12 wherein R.sup.12 is a saturated or unsaturated linear hydrocarbon chain of 5-20 carbons optionally containing one or more interruptions within the chain by a heteroatom, and optionally substituted with one or more .dbd.O, or .dbd.S. Finally, X.sup.12 is selected from the group consisting of hydroxy, an aminoalkyl group, and a known amino acid bound by its .alpha.Type: GrantFiled: June 7, 1995Date of Patent: November 30, 1999Assignee: Biochem PharmaInventors: Christopher Penney, Boulos Zacharie, Lyne Gagnon, Giorgio Attardo, Timothy P. Connolly, Yves St-Denis, Salam Kadhim
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Substituted xanthines and their use in the treatment of cerebrovascular disorders and other diseases
Patent number: 5981535Abstract: A method for the treatment of cerebrovascular disorders and/or disorders associated with cerebral senility and/or allergic disorders, proliferative skin disorders, and bronchodilation which method comprises the administration of an effective, non-toxic amount of a compound of formula (I): ##STR1## or if appropriate a pharmaceutically acceptable salt thereof, wherein R.sup.1 and R.sup.2 each independently represent alkyl or a moiety of formula (a):--(CH.sub.2).sub.m --A (a)wherein m represents zero or an integer 1, 2 or 3; A represents a substituted or unsubstituted cyclic hydrocarbon radical; andR.sup.3 represents a halogen atom, a nitro group, or a group --NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 each independently represents hydrogen, alkyl or alkylcarbonyl or R.sup.4 and R.sup.5 together with the nitrogen to which they are attached forming an optionally substituted, heterocyclic group; certain novel compounds falling within formula (I) and compositions comprising such compounds.Type: GrantFiled: June 7, 1995Date of Patent: November 9, 1999Assignee: SmithKline Beecham p.l.c.Inventors: Barbara Ann Spicer, Harry Smith, Harald Maschler -
Patent number: 5968940Abstract: New purine retinoid compounds according to the formula: ##STR1## wherein R is a purine derivative, and pharmaceutical compositions thereof, are provided which exhibit cancer-inhibiting activity.Type: GrantFiled: June 7, 1996Date of Patent: October 19, 1999Assignee: Institute of Materia MedicaInventors: Rui Han, Zang-Liang Yuan
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Patent number: 5942617Abstract: A process for preparing 7-benzylpurine derivatives is provided. An acetylpurine nucleoside is reacted with a benzyl halide to benzylate the 7-position of the purine base, and an acid is then added to the reaction mixture to hydrolyze the glycoside bond. The 7-benzylpurines may be used to prepare 9-substituted purine derivatives.Type: GrantFiled: September 10, 1997Date of Patent: August 24, 1999Assignee: Ajinomoto Co., Inc.Inventors: Hiroshi Shiragami, Yumiko Uchida, Kunisuke Izawa, Keizo Yamashita, Satoshi Katayama
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Patent number: 5922868Abstract: Use of xanthine derivatives for the treatment of nerve damage following an interruption in blood circulation.The invention relates to the use of xanthine derivatives of the formula I ##STR1## in which R.sup.2 is a (C.sub.1 -C.sub.4)-alkyl group and at least one of the symbols R.sup.1 and R.sup.3 is a radical of the formula II or III ##STR2## in which A is CHOH, CO or dioxolane, R.sup.4 is a hydrogen atom or a (C.sub.1 -C.sub.4)-alkyl group and n is 0 to 5, and in which R.sup.5 and R.sup.6 are hydrogen atoms or (C.sub.1 -C.sub.4)-alkyl groups or, together with the nitrogen atom to which they are bonded, form a 5- to 7-membered ring, it being possible for one carbon atom to be replaced by an oxygen or nitrogen atom, m is 1 or 2 and the other radical R.sup.1 or R.sup.3, if appropriate, is a hydrogen atom, a (C.sub.1 -C.sub.6)-alkyl group or a (C.sub.3 -C.sub.Type: GrantFiled: December 22, 1995Date of Patent: July 13, 1999Assignee: Hoechst AktiengesellschaftInventors: Werner Thorwart, Harald Furrer, Erhard Wolf, Ulrich Gebert, Erhard Rossmanith, John J. Grome, Ernst-Jurgen Schneider
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Patent number: 5919789Abstract: Compounds of the formula (i) ##STR1## have therapeutic utility via inhibition of TNF or phophodiesterase.Type: GrantFiled: November 17, 1997Date of Patent: July 6, 1999Assignee: Darwin Discovery LimitedInventors: Hazel Joan Dyke, John Gary Montana
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Patent number: 5861405Abstract: The present invention provides 8-substituted 1,3,7-trialkylxanthines useful as A.sub.2 -selective adenosine receptor antagonists and compositions comprising such compounds. Examples of the 8-substituted 1,3,7-trialkyl xanthines include: ##STR1## In compound (a), R.sub.1, R.sub.3, and R.sub.7 are methyl and X is one to three substituents, which may be the same or different and selected from the group consisting of amino, C.sub.1 -C.sub.4 alkylcarbonylamino, carboxy C.sub.2 -C.sub.4 alkylcarbonylamino, halo, C.sub.1 -C.sub.3 alkyloxy, amino C.sub.1 -C.sub.4 alkyloxy, C.sub.1 -C.sub.4 alkyloxy carbonylamino, amino C.sub.1 -C.sub.4 alkenyloxy, isothiocyanato, and diazonium tetrafluoroborate. In compound (b), R.sub.1, R.sub.3, and R.sub.7 are methyl, R.sub..beta. is hydrogen or methyl, and X is selected from the group consisting of R, C(.dbd.O)OR, and C(.dbd.O)NH--R, wherein R is a C.sub.1 -C.sub.6 alkyl.Type: GrantFiled: November 7, 1994Date of Patent: January 19, 1999Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Kenneth A. Jacobson, Yishai Karton, Carola Gallo-Rodriguez, Bilha Fischer, Philip J. M. van Galen, Michel Maillard
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Patent number: 5861403Abstract: The present invention relates to compounds of the formula ##STR1## wherein HET is ##STR2## m is an integer from 1 to 4; R.sup.1 and R.sup.Type: GrantFiled: October 2, 1996Date of Patent: January 19, 1999Assignee: G. D. Searle & Co.Inventors: Ish Kumar Khanna, Richard Mathias Weier
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Patent number: 5831092Abstract: Purine derivatives in which a desired substituent is introduced into the 9-position only are synthesized by first introducing an easily-removable substituent in the 7-position of a purine base of natural purine nucleosides obtained through fermentation or derivatives thereof, then hydrolyzing the ribose moiety to form purine derivatives having the substituent in the 7-position, subsequently introducing the desired substituent in the 9-position, and then removing the substituent in the 7-position.Type: GrantFiled: February 20, 1996Date of Patent: November 3, 1998Assignee: Ajinomoto Co., Inc.Inventors: Kunisuke Izawa, Hiroshi Shiragami, Keizo Yamashita
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Patent number: 5821366Abstract: 1,3-Disubstituted-zanthines have therapeutic utility via TNF or phosphodiesterase inhibition.Type: GrantFiled: May 20, 1996Date of Patent: October 13, 1998Assignee: Chiroscience LimitedInventor: John Gary Montana
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Patent number: 5807854Abstract: Compounds of general formula I and their salts and solvates are antifungal agents and as such are useful in the treatment of various fungal infections. Pharmaceutical compositions including these compounds and processes for their preparation are also provided.Type: GrantFiled: March 31, 1997Date of Patent: September 15, 1998Assignee: J. Uriah & Cia. S.A.Inventors: Javier Bartroli, Enric Turmo, Manuel Anguita
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Patent number: 5786360Abstract: A compound useful as an A.sub.1 adenosine receptor antagonist has the formula: ##STR1## wherein R.sub.1 is selected from the group consisting of C.sub.1 -C.sub.8 alkyl;R.sub.2 is of the formula: ##STR2## wherein n is an integer ranging from 1 to 8; R.sub.5 is H or (CH.sub.2).sub.p, wherein p is an integer ranging from 1 to 8; and R.sub.6 is H or (CH.sub.2).sub.m OH, wherein m is an integer ranging from 1 to 8;R.sub.3 is of the formula:--(CH.sub.2).sub.q C.sub.6 H.sub.4 --R.sub.7wherein q is an integer ranging from 1 to 8; and wherein R.sub.7 is selected from the group consisting of H, NH.sub.2, (CH.sub.2).sub.t OH, wherein t is an integer ranging from 1 to 8; and R.sub.9 COOH, wherein R.sub.9 is an alkyl or alkylidene group having 1 to 8 carbon atoms; andR.sub.4 is of the formula: ##STR3## wherein R.sub.8 is selected from the group consisting of H; NH.sub.2 ; (CH.sub.2).sub.t OH, wherein s is an integer ranging from 1 to 8; and R.sub.10 COOH, wherein R.sub.Type: GrantFiled: November 19, 1996Date of Patent: July 28, 1998Assignee: Link Technology IncorporatedInventor: Constance Neely
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Patent number: 5776940Abstract: The present invention relates to novel compounds of formula (I), processes for their preparation, pharmaceutical formulations containing them, and their use in medicine, particularly in the prophylaxis and treatment of septic shock, allergic, and inflammatory conditions, as well as neurodegeneration.Type: GrantFiled: January 24, 1997Date of Patent: July 7, 1998Assignee: Glaxo Wellcome Inc.Inventors: Susan Mary Daluge, Helen Lyng White
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Patent number: 5770595Abstract: Oxime-substituted compounds are preferably cyclic or heterocyclic compounds. The oxime-substituted compounds and pharmaceutical compositions thereof have the formula:CORE MOIETY--(R).sub.jincluding resolved enantiomers (both syn and anti forms) and/or diastereomers, hydrates, salts, solvates and mixtures thereof. j is an integer from one to three, the core moiety is non-cyclic or cyclic and R may be selected from among: hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted C.sub.(1-10), alkyl, C.sub.(2-10) alkenyl, cyclic or heterocyclic groups, and formula I. At least one R has the formula I:--(CH.sub.2).sub.n --C--(R.sub.1).sub.p, Iwherein n is an integer from three to twenty; p is two or three; R.sub.1 is selected from among hydrogen; halogen; hydroxide; substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(1-10) alkoxy, C.sub.(2-10) alkenyl, cyclic or heterocyclic group; =N--OR.sub.2, R.sub.2 being hydrogen or a substitute or unsubstituted C.sub.(1-10) alkyl, C.sub.Type: GrantFiled: February 7, 1994Date of Patent: June 23, 1998Assignee: Cell Therapeutics, Inc.Inventors: J. Peter Klein, Alistair Leigh
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Patent number: 5753635Abstract: This invention is directed to purine derivatives of the following formulae: ##STR1## wherein Z.sup.1 is --O--, --N(R.sup.10)-- or --CH.sub.2 O--;Z.sup.2 is --O--, --N(R.sup.10)-- or --OCH.sub.2 --;R.sup.1 and R.sup.4 are each independently hydrogen, halo, alkyl, --OR.sup.10, --C(O)OR.sup.10, --C(O)N(R.sup.10)R.sup.11, --N(R.sup.10)R.sup.11, --N(R.sup.10)C(O)R.sup.10, or --N(H)S(O).sub.2 R.sup.13 ;R.sup.2 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.10, --C(NH)N(H)C(O)OR.sup.13, --C(NH)N(H)C(O)R.sup.10, --C(NH)N(H)S(O).sub.2 R.sup.13, or --C(NH)N(H)C(O)N(H)R.sup.10 ;R.sup.3 is halo, alkyl, haloalkyl, haloalkoxy, ureido, cyano, guanidino, --OR.sup.10, --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.10, --C(O)N(R.sup.10)R.sup.11, --R.sup.12 --C(O)N(R.sup.10)R.sup.11, --CH(OH)C(O)N(R.sup.10)R.sup.11, --N(R.sup.10)R.sup.11, --R.sup.12 --N(R.sup.10)R.sup.11, --C(O)OR.sup.10, --R.sup.12 --C(O)OR.sup.10, --N(R.sup.10)C(O)R.sup.Type: GrantFiled: August 16, 1996Date of Patent: May 19, 1998Assignee: Berlex Laboratories, Inc.Inventors: Brad O. Buckman, Raju Mohan, Michael M. Morrissey
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Patent number: 5734051Abstract: A method for the treatment of cerebrovascular disorders and/or disorders associated with cerebral senility and/or other disorders which method comprises the administration of an effective, non-toxic amount of a compound of formula (I): ##STR1## or if appropriate a pharmaceutically acceptable salt thereof, wherein R.sup.1 and R.sup.2 each independently represent alkyl or a moiety of formula (a):--(CH.sub.2).sub.m --A (a)whereinm represents zero or an integer 1, 2 or 3;A represents a substituted or unsubstituted cyclic hydrocarbon radical; andR.sup.3 represents a halogen atom, a nitro group, or a group --NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 each independently represents hydrogen, alkyl or alkylcarbonyl or R.sup.4 and R.sup.5 together with the nitrogen to which they are attached forming an optionally substituted, heterocyclic group; certain novel compounds falling within formula (I) and compositions comprising such compounds.Type: GrantFiled: June 7, 1995Date of Patent: March 31, 1998Assignee: Beecham GroupInventors: Barbara Ann Spicer, Harry Smith, Harald Maschler
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Patent number: 5719279Abstract: Xanthine derivatives of formula ##STR1## wherein R.sub.1 is hydrogen, alkyl or alkynyl,R.sub.2 is different and is alkyl, alkynyl, phenyl-alkylene, phenyl alkenylene, cycloalkyl, inter alia,R.sub.3 is cycloalkyl, phenyl, norbornane, inter alia andR.sub.4 is hydrogen, methyl, benzyl, inter alia.Type: GrantFiled: June 11, 1996Date of Patent: February 17, 1998Assignee: Boehringer Ingelheim KGInventors: Ulrike Kufner-Muhl, Helmut Ensinger, Joachim Mierau, Franz Josef Kuhn, Erich Lehr, Enzio Muller
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Patent number: 5714494Abstract: Substituted xanthines of formula ##STR1## in which A represents a radical of the formula ##STR2## in which R.sup.3, R.sup.4, R.sup.6 and R.sup.7 denote hydrogen, cycloalkyl, aryl having 6 to 10 carbon atoms, or denote straight-chain of branched alkyl or alkenyl, each of which is optionally substituted; T, V, X and Y are identical or different and denote an oxygen or sulphur atom; R.sup.5 and R.sup.8 are identical or different and denote hydrogen, halogen, cycloalkyl having 3 to 8 carbon atoms or straight-chain or branched alkyl or alkenyl in each case having up to 8 carbon atoms, optionally substituted or R.sup.5 and R.sup.8 denote aryl having 6 to 10 carbon atoms or a 5- to 7-membered aromatic, optionally benzo-fused heterocycle having up to 3 heteroatoms S, N and/or O, each of which is optionally substituted; L represents an oxygen or sulphur atom; R.sup.2 represents mercapto, hydroxyl, straight-chain or branched alkoxy having up to 8 carbon atoms or the group of the formula ##STR3## in which R.sup.Type: GrantFiled: September 18, 1996Date of Patent: February 3, 1998Assignee: Bayer AktiengesellschaftInventors: Richard Connell, Siegfried Goldmann, Ulrich Muller, Stefan Lohmer, Hilmar Bischoff, Dirk Denzer, Rudi Grutzmann, Stefan Wohlfeil
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Patent number: 5710272Abstract: A Rhodotorula rubra strain has been found which reduces pentoxifylline to 100% to give the S-alcohol. Moreover, other oxoalkylxanthine derivatives can also be convened into the corresponding S-alcohol. The microbiologically obtained S-(+)-enantiomers can then be converted stereoselectively into the respective R-(-)-enantiomers. The corresponding S-alcohols and the R-alcohols obtained by enantioselective inversion of configuration cause an increase in cerebral blood flow.Type: GrantFiled: June 7, 1995Date of Patent: January 20, 1998Assignee: Hoechst AktiengesellschaftInventors: Werner Aretz, Harald Furrer, Ulrich Gebert, Heinz-Joachim Hinze
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Patent number: 5703085Abstract: The present invention relates to novel xanthine derivatives and pharmaceutically acceptable salts thereof, represented by Formula (I): ##STR1## wherein R.sup.1, R.sup.2, and R.sup.3 independently represent hydrogen, lower alkyl, lower alkenyl, or lower alkynyl, R.sup.4 represents lower alkyl, or substituted or unsubstituted aryl, R.sup.5 and R.sup.6 independently represent hydrogen, lower alkyl, and lower alkoxy, or R.sup.5 and R.sup.6 are combined together to represent --O--(CH.sub.2)p--O-- (p is an integer of 1 to 3), n represents 0, 1, or 2, and m represents 1 or 2.The compounds of the present invention have an adenosine A.sub.2 receptor antagonistic activity, and are useful for the treatment or prevention of various kinds of diseases caused by hyperergasia of adenosine A.sub.2 receptors (for example, Parkinson's disease, senile dementia, depression, asthma, and osteoporosis).Type: GrantFiled: October 20, 1995Date of Patent: December 30, 1997Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Fumio Suzuki, Nobuaki Koike, Junichi Shimada, Joji Nakamura, Shizuo Shiozaki, Shigeto Kitamura, Shunji Ichikawa, Hiroshi Kase, Hiromi Nonaka
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Patent number: 5674998Abstract: This invention relates to adenosine kinase inhibitors and to nucleoside analogs, C-4' modified pyrrolo?2,3-d!pyrimidine and pyrazolo?3,4-d!pyrimidine nucleoside analogs having activity as adenosine kinase inhibitors. The invention relates to nucleoside analogs of this kind, having zero substitutions or two substitutions at the C-4' position of the furanose (sugar) moiety. The invention also relates to the preparation and use of these adenosine kinase inhibitors in the treatment of cardiovascular, and cerebrovascular diseases, inflammation and other diseases which can be regulated by increasing the local concentration of adenosine.Type: GrantFiled: June 7, 1995Date of Patent: October 7, 1997Assignee: Gensia Inc.Inventors: Serge H. Boyer, Mark D. Erion, Bheemarao G. Ugarkar
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Process for preparing xanthine derivatives, in particular 1,3-dipropyl-8-(3-oxocyclopentyl)-xanthine
Patent number: 5675005Abstract: This invention relates to a process for preparing xanthine derivatives of formula I: ##STR1## characterized in that a uracil derivative of formula A or B ##STR2## is dissolved in a suitable organic-aqueous solvent and cyclized in the presence of LiOH.Type: GrantFiled: March 7, 1995Date of Patent: October 7, 1997Assignee: Boehringer Ingelheim KGInventors: Ulrike Kufner-Muhl, Sven Luttke -
Patent number: 5670498Abstract: Disclosed are xanthine derivatives represented by the following Formula (I): ##STR1## in which R.sup.1, R.sup.2, and R.sup.3 independently represent hydrogen or lower alkyl;Q.sup.1, Q.sup.2, and Q.sup.3 independently represent hydrogen, lower alkyl, lower alkoxy, or halogen;and X represents --COR.sup.4 (in which R.sup.4 represents hydrogen, hydroxy, lower alkyl, or lower alkoxy) or --SO.sub.2 R.sub.5 {in which R.sup.5 represents hydroxy, lower alkoxy, trifluoromethyl, ##STR2## in which R.sup.6 and R.sup.7 independently represent hydrogen, hydroxy-substituted or unsubstituted lower alkyl, aryl, or ##STR3## (in which m represents an integer of 1 to 3; and R.sup.8 and R.sup.9 independently represent hydrogen or lower alkyl), or ##STR4## (in which Y represents a single bond, oxygen, or N--R.sup.10 in which R.sup.10 represents hydrogen or lower alkyl; and n1 and n2 independently represent an integer of 1 to 3)}, and pharmaceutically acceptable salts thereof.Type: GrantFiled: September 13, 1995Date of Patent: September 23, 1997Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Fumio Suzuki, Junichi Shimada, Nobuaki Koike, Hiroshi Kase, Joji Nakamura, Shizuo Shiozaki, Hiromi Nonaka
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Patent number: 5532368Abstract: Xanthines of the formula I ##STR1## wherein R.sub.1 is a C.sub.1 -C.sub.4 alkyl group:R.sub.2 is a C.sub.1 -C.sub.4 alkyl group;R.sub.3 tetrahydropyran-4-yl or 1,3-dithiolan or;R.sub.3 represents one of the groups of formula ##STR2## and pharmaceutically acceptable acid addition salts thereof. These are adenosine antagonists, capable of acting as cholinomimetics, useful for the treatment of CNS disorders such as senile dementia and Alzheimer's disease.Type: GrantFiled: July 27, 1993Date of Patent: July 2, 1996Assignee: Boehringer Ingelheim GmbHInventors: Ulrike Kufner-Muhl, Karl-Heinz Weber, Gerhard Walther, Werner Stransky, Helmut Ensinger, Gunter Schingnitz, Franz J. Kuhn, Erich Lehr
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Patent number: 5506347Abstract: Novel lyxose derivatives which selectively inhibit adenosine kinase and methods of preparing these compounds are provided. These compounds are useful in treating certain conditions in vivo which may be ameliorated by increased local concentrations of adenosine.Type: GrantFiled: February 3, 1994Date of Patent: April 9, 1996Assignee: Gensia, Inc.Inventors: Mark D. Erion, Bheemarao G. Ugarkar, Angelo J. Castellino
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Patent number: 5478830Abstract: This invention relates to pyrazolo pyrimidines for the treatment of atherosclerosis as inhibitors of acyl--CoA, cholesterol acyetransferase (ACAT), and their use as antihypercholesterolemic agents, pharmaceutical compositions and preparation, and having the formula (I): ##STR1## wherein: A and Q are selected independently from CH or N with no more than two nitrogens per ring:D, E, and G are selected independently from CR.sup.1 or N with no more than two nitrogens per ring;X is S(O).sub.r, O, NR.sup.4 or CH.sup.2 ;J is C.sub.2 -C.sub.10 alkyl, C.sub.3 -C.sub.10 branched alkyl, C.sub.3 -C.sub.10 alkenyl or C.sub.3 -C.sub.10 alkynyl;Y is O, S, H.sub.2 or NH:Z is NHR.sup.3, OR.sup.3 or R.sup.3 :R.sup.1 is selected independently from H, NO.sub.2, Br, Cl, F, CF.sub.3, CN, CH.sub.3 S(O).sub.r, C.sub.1 -C.sub.8 alkyl or alloxy, C.sub.3 -C.sub.8, branched alkyl, C.sub.1 -C.sub.4 carboalkoxy, NR.sup.5 R.sup.6 or NR.sup.5 COR.sup.6 ;R.sup.2 is C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 branched alkyl, C.sub.3 -C.sub.Type: GrantFiled: May 29, 1992Date of Patent: December 26, 1995Assignee: The Du Pont Merck Pharmaceutical CompanyInventors: C. Anne Higley, Ruth R. Wexler, Richard G. Wilde
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Patent number: 5475107Abstract: Process for obtaining 3,7-dialkylxanthines from 3-alkyl-xanthines3,7-Dialkylxanthines are obtained from the corresponding 3-alkylxanthines using an alkylating agent in the presence of quaternary ammonium and/or phosphonium compounds and, where appropriate, of additional polyethers in a two-phase mixture.Type: GrantFiled: November 9, 1993Date of Patent: December 12, 1995Assignee: Hoechst-Roussel Pharmaceuticals IncorporatedInventors: Gerhard Korb, Hans-Wolfram Flemming
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Patent number: 5470858Abstract: A compound represented by the following formula I:(HET)Ar--X--CH.sub.2 --Y--CH.sub.2 --O--R (I)wherein:(HET)Ar represents a bicyclic hetero aryl nucleus which is unsubstituted or is substituted;X represents --S--;Y represents --CO--, --C.dbd.N--R.sub.2, in which R.sub.2 is hydrogen or a linear or branched alkyl having 1 to 10 carbon atoms, OH, an alkoxy having 1 to 10 carbon atoms, aryloxy, arylalkoxy, --NH.sub.2, --NHCONH.sub.2, --NHCSNH.sub.2 ; and R represents a phenyl substituted at para position with a carboxyl or a (C.sub.1 -C.sub.20) alkoxycarbonyl group in which the alkoxy group is linear or branched.Type: GrantFiled: June 19, 1992Date of Patent: November 28, 1995Assignee: Pierrel SpAInventors: Cristina Fraire, Massimo Bani, Ermes Vanotti, Vincenzo Olgiati
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Patent number: 5461059Type: GrantFiled: March 26, 1993Date of Patent: October 24, 1995Assignee: Laboratoire Theramex S.A.Inventors: Paule Bonnet, Remi Delansorne, Maurice Faure, Michel Languetin, Serge Zunino
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Patent number: 5446046Abstract: Adenosine and xanthine derivatives, and compositions comprising those compounds, are potent selective agonists and antagonists of adenosine receptors. The derivatives and composition are used to treat conditions, including certain cardiac arrhythmias.Type: GrantFiled: October 28, 1993Date of Patent: August 29, 1995Assignee: University of Florida Research FoundationInventors: Luiz Belardinelli, Ray Olsson, Stephen Baker, Peter J. Scammells
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Patent number: 5434150Abstract: The invention relates to cyclic imino derivatives of general formula ##STR1## wherein A to G, R.sub.1, Z.sub.1 to Z.sub.6, X and Y are defined as in claim 1, the tautomers, stereoisomers and mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable pharmacological properties, preferably aggregation-inhibiting properties, pharmaceutical compositions which contain these compounds and processes for preparing them.Type: GrantFiled: August 28, 1992Date of Patent: July 18, 1995Assignee: Dr. Karl Thomae GmbHInventors: Volhard Austel, Helmut Pieper, Frank Himmelsbach, Guenter Linz, Thomas Mueller, Johannes Weisenberger, Elke Seewaldt-Becker
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Patent number: 5409935Abstract: The use of xanthine derivatives for the treatment of secondary nerve cell damage and functional disorders after cranio-cerebral traumas (CCT)The use of xanthine derivatives of the formula I ##STR1## and of their physiologically tolerable salts, in which R.sup.1 is oxoalkyl, hydroxyalkyl or alkyl, R.sup.2 is hydrogen or alkyl and R.sup.3 is hydrogen, alkyl, oxoalkyl or an alkyl having up to 6 carbon atoms, whose carbon chain is interrupted by an oxygen atom, for the production of pharmaceuticals for the treatment of disorders which can occur after cranio-cerebral traumas is described.Type: GrantFiled: July 9, 1992Date of Patent: April 25, 1995Assignee: Hoechst AktiengesellschaftInventors: Hans-Peter Schubert, John J. Grome, Barbara Kittner, Karl Rudolphi, Ulrich Gebert
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Patent number: 5332744Abstract: Substituted Imidazo-fused 6-membered heterocycles of structural formula: ##STR1## wherein A, B, C, and D are independently carbon atoms or nitrogen atoms are angiotensin II antagonists useful in the treatment of hypertension and congestive heart failure.Type: GrantFiled: May 4, 1990Date of Patent: July 26, 1994Assignee: Merck & Co., Inc.Inventors: Prasun K. Chakravarty, William J. Greenlee, Nathan B. Mantlo, Arthur A. Patchett, Thomas F. Walsh
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Patent number: 5332814Abstract: Process for the preparation of racemic compounds of the formula I ##STR1## or enantiomers thereof, in which B is the radical of a nucleic base from the series comprising purine, a purine analogue or a pyridine analogue, and R is H or a protective group R.sub.1, by reactinga) a compound of the formula II or enantiomer thereof ##STR2## with a compound of the formulae X--CO--X, X--CS--X, X--SO--X, X--SO.sub.2 --X, R.sub.2 --NCO, R.sub.3 R.sub.4 N--C(O)--R.sub.5, X.sub.2 P--R.sub.6 or X.sub.2 P(O)--R.sub.6, in which X is a leaving group, R.sub.2 is, for example, C.sub.1 -C.sub.18 alkyl, R.sub.3 and R.sub.4 are, for example, H or C.sub.1 -C.sub.18 alkyl, R.sub.5 is, for example, H or C.sub.1 -C.sub.12 alkyl, and R.sub.6 is, for example, C.sub.1 -C.sub.12 alkyl or C.sub.1 -C.sub.12 alkoxy, to give a compound of the formula III or enantiomers thereof ##STR3## in which Y is the groups --C(O)--, --C(S)--, --SO--, --SO.sub.2 --, R.sub.2 NH--CH.dbd., R.sub.3 R.sub.4 N--CR.sub.5 .dbd., R.sub.6 P.dbd. and R.sub.6 (O)P.Type: GrantFiled: October 30, 1992Date of Patent: July 26, 1994Assignee: Ciba-Geigy CorporationInventor: Heinz Moser
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Patent number: 5321029Abstract: A compound of formula (I): ##STR1## or where appropriate a pharmaceutically acceptable salt thereof, wherein R.sup.1 and R.sup.2 each independently represent a moiety of formula (a):--(CH.sub.2).sub.m --A (a)wherein m represents zero or an integer 1, 2 or 3, A represents a substituted or unsubstituted cyclic hydrocarbon radical; andR.sup.3 represents hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl or a moiety of formula (a) as defined above; a pharmaceutical composition comprising such a compound a process for preparing such a compound and the use of said compound and said composition in medicine.Type: GrantFiled: January 13, 1992Date of Patent: June 14, 1994Assignee: Beecham-Wuelfing GmbH & Co.K.G.Inventors: Harald Maschler, Rolf T. Wilke, Johannes Jukna
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Patent number: 5310916Abstract: Trifunctional agents useful as inhibitors of A.sub.1 -Adenosine receptors may be formulated into pharmaceutical compositions. These agents are represented by formula (I): ##STR1## wherein X is CH or N, R is an isothiocyanate group, an amino group or --NHCO.sub.2 C(CH.sub.3).sub.3 and R.sup.1 is hydrogen, carboxyl, lower alkoxycarbonyl, aminocarbonyl, ##STR2## lower alkyl, optionally substituted with: --OH, --COOH, lower ester of COOH, carboxamide, NHCOCH.sub.3, NHCOCH.sub.2 Br, halo, dimethylamino, triethylammonium, NHCONH.sub.2, SO.sub.2 NH.sub.2, --SO.sub.3 H, or a reporter group, particularly a spectroscopic reporter group such as a fluorescent dye, photoaffinity probe, or spin label probe, coupled through an amide, sulfonamide, amine or thiourea linkage, biotinylamino- (optionally containing an .epsilon.-aminocaproyl spacer chain or similar spacer chain) or; R.sup.1 is CONH--R.sup.2 or NHCSNH--R.sup.2, wherein R.sup.Type: GrantFiled: August 24, 1990Date of Patent: May 10, 1994Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Kenneth A. Jacobson, Gary L. Stiles, Daniel L. Boring
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Patent number: 5284837Abstract: Antivirally active compounds of formula (I), wherein R.sup.1 is hydrogen, hydroxy, mercapto or amino; R.sup.2 is hydrogen, hydroxy, fluoro, chloro or amino; R.sup.3 and R.sup.4 are independently selected from (II), (III), amino, hydroxy or an ether or ester residue thereof, or R.sup.3 together with R.sup.4 is (IV), wherein M is hydrogen or a pharmaceutically acceptable counterion; and n is 1 or 2; with the proviso that, when R.sup.2 is amino and R.sup.3 and R.sup.4 are hydroxy R.sup.1 is not hydroxy and in addition, when n=1, R.sup.1 is not hydrogen, and pharmaceutically acceptable salts thereof; processes for preparation of said compounds, a pharmaceutical composition comprising said compounds, methods for treatments of virus infections as well as use of compounds of formula (I) without the proviso for the manufacture of a medicament for treatment of AIDS.Type: GrantFiled: December 26, 1990Date of Patent: February 8, 1994Assignee: Medivir ABInventors: Bjorn G. Lindborg, Roelf Datema, Karl N. G. Johansson, Bo F. berg
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Patent number: 5281605Abstract: A compound of formula I ##STR1## wherein R.sub.1 is C.sub.1-4 alkyl, C.sub.3-4 alkenyl or (C.sub.3-5 cycloalkyl)-methyl, R.sub.2 is C.sub.1-4 alkyl, [hydroxy- or (C.sub.1-4 alkoxy)-substituted C.sub.1-3 alkyl]-methyl, (C.sub.3-5 cycloalkyl)-methyl, tetrahydrofuran 2-yl-methyl or 1,3-dioxolan-2-yl-methyl, R.sub.3 and R.sub.4 are each hydrogen, hydroxymethyl, methoxymethyl or N,N-dimethylcarbamoyloxymethyl, R.sub.5 is hydroxy or methoxy, R.sub.6 is hydrogen, hydroxy, methoxy or halogen and R.sub.7 is in the 2- or 3-position and is hydroxy, methoxy or halogen, or together with R.sub.5 is 3,4-methylendioxy, or together with R.sub.6 is 2,3-methylenedioxy and their physiologically-hydrolysable and -acceptable esters are useful in the treatment (symptomatic and prophylactic) of obstructive or inflammatory airways disease, in particular asthma, and disease characterised by or having an aetiology comprising morbid eosinophil accumulation or activation, e.g. hypereosinophilia.Type: GrantFiled: September 27, 1991Date of Patent: January 25, 1994Assignee: Sandoz Ltd.Inventors: Zoltan L. Kis, John Morley
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Patent number: 5278165Abstract: Oxazolyl derivatives of formula (I) ##STR1## wherein --A.sup.1 .dbd.A.sup.2 --A.sup.3 .dbd.A.sup.4 -- represents a bivalent radical having the formula--CH.dbd.CH--CH.dbd.CH-- (a-1),--N.dbd.CH--CH.dbd.CH-- (a-2),--CH.dbd.N--CH.dbd.CH-- (a-3),--CH.dbd.CH--N.dbd.CH-- (a-4),--CH.dbd.CH--CH.dbd.N-- (a-5),--N.dbd.CH--N.dbd.CH-- (a-6)or--CH.dbd.N--CH.dbd.N-- (a-7);R represents hydrogen or C.sub.1-4 alkyl; R.sup.1 represents hydrogen, C.sub.1-6 alkyl or hydroxyC.sub.1-6 alkyl; m represents 1 or 2; D represents C.sub.1-4 alkanediyl; B represents NR.sup.2, CH.sub.2, O, S, SO or SO.sub.2 wherein R.sup.2 is hydrogen or C.sub.1-4 alkyl; n represents 0, 1 or 2; L represents hydrogen; C.sub.1-12 alkyl; C.sub.3-6 cycloalkyl; C.sub.3-6 alkenyl optionally substituted with aryl; C.sub.1-6 alkylcarbonyl; C.sub.1-6 alkyloxycarbonyl; arylcarbonyl; arylC.sub.1-6 alkyloxycarbonyl; or a radical of formula --Alk--R.sup.3 (b-1); --Alk--Y--R.sup.4 (b-2); --Alk--Z.sup.1 --C(.dbd.X)--Z.sup.2 --R.sup.5 (b-3); or --CH.sub.2 --CHOH--CH.sub.Type: GrantFiled: March 23, 1993Date of Patent: January 11, 1994Assignee: Janssen Pharmaceutica N.V.Inventors: Frans E. Janssens, Francois M. Sommen, Ann C. J. Dierckx, Ludwig P. Cooymans
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Patent number: 5175291Abstract: A process for preparing 1,3-dipropyl-8-(3-oxocyclopentyl)-xanthine.Type: GrantFiled: April 25, 1991Date of Patent: December 29, 1992Assignee: Boehringer Ingelheim KGInventor: Ulrike Kufner-Muhl
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Patent number: 5175290Abstract: 1,3-Substituted-8-(oxo-substituted cycloalkyl)xanthines and pharmaceutically acceptable salts of such compounds are disclosed. Preferred compounds include the cis and trans isomers of 1,3-dipropyl-8-(3-hydroxycyclopentyl)xanthine and the cis and trans isomers of 1,3-dipropyl-8-(4-hydroxycyclohexyl)xanthine. The compounds are potent and selective bronchodilators and/or cardiotonic agents.Type: GrantFiled: September 16, 1988Date of Patent: December 29, 1992Assignee: Marion Merrell Dow Inc.Inventors: Waclaw J. Rzeszotarski, Roger N. Hiner, Scott W. Feeney
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Patent number: 5175288Abstract: A process for preparing pharmaceutically active compounds of formula (A): ##STR1## wherein X is hydrogen, hydroxy, chloro, C.sub.1-6 alkoxy or phenyl C.sub.1-6 alkoxy; and R.sub.a and R.sub.b are hydrogen, or acyl or phosphate derivatives thereof, which process comprises the preparation of an intermediate of formula (I): ##STR2## wherein R.sub.1 is C.sub.1-6 alkyl, or phenyl C.sub.1-6 alkyl in which the phenyl group is optionally substituted; R.sub.2 is hydrogen, hydroxy, chlorine, C.sub.1-6 alkoxy, phenyl C.sub.1-6 alkoxy or amino; and R.sub.3 is halogen, C.sub.1-6 alkylthio, C.sub.1-6 alkylsulphonyl, azido, an amino group or a protected amino group, via the reaction of a compound of formula (II): ##STR3## wherein R.sub.2 and R.sub.3 are as defined for formula (I) with: (a) a compound of formula (III): ##STR4## wherein R.sub.4 and R.sub.5 are independently hydrogen, C.sub.1-6 alkyl, or phenyl, or R.sub.4 and R.sub.5 together are C.sub.Type: GrantFiled: April 9, 1990Date of Patent: December 29, 1992Assignee: Beecham Group p.l.c.Inventors: Trevor J. Grinter, Graham R. Geen, Martin J. Parratt
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Patent number: 5171353Abstract: Sulfonamides of the general formula I ##STR1## where R.sup.1 is hydrogen of C.sub.1 -C.sub.4 -alkyl,R.sup.2 is hydrogen or substituted or unsubstituted C.sub.1 -C.sub.6 -alkyl; C.sub.3 -C.sub.4 -alkenyl; C.sub.3 -C.sub.4 -alkynyl or substituted or unsubstituted saturated or singly unsaturated 5- to 7- membered heteroaryl;R.sup.3 and R.sup.4 are halogen; substituted or unsubstituted C.sub.1 -C.sub.4 -alkoxy C.sub.1 -C.sub.4 -alkylthio, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkenyloxy, C.sub.2 -C.sub.6 -alkenylthio, C.sub.2 -C.sub.6 -alkynyl, C.sub.2 -C.sub.6 -alkynyloxy, C.sub.2 -C.sub.6 -alkynylthio, C.sub.3 -C.sub.6 -cycloalkyl, C.sub.3 -C.sub.6 -cycloalkylthio, C.sub.5 -C.sub.6 -cycloalkenyl, C.sub.3 -C.sub.6 -cycloalkoxy, C.sub.5 -C.sub.6 -cycloalkenyloxy, C.sub.5 -C.sub.6 -cycloalkenylthio, phenyl, phenoxy, phenylthio, benzyl, benzyloxy or benzylthio;the group given for R.sup.2, or NR.sup.7 R.sup.8, where R.sup.7 and R.sup.8 are hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.3 -C.sub.6 -alkenyl, C.sub.Type: GrantFiled: May 9, 1990Date of Patent: December 15, 1992Assignee: BASF AkteingesellschaftInventors: Klaus Fischer, Horst Mayer, Klaus Ditrich, Gerhard Hamprecht, Bruno Wuerzer, Karl-Otto Westphalen
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Patent number: 5157026Abstract: Substituted Imidazo-fused 6-membered heterocycles of structural formula: ##STR1## wherein A, B, C, and D are independently carbon atoms or nitrogen atoms are angiotensin II antagonists useful in the treatment of hypertension and congestive heart failure.Type: GrantFiled: February 24, 1992Date of Patent: October 20, 1992Assignee: Merck & Co., Inc.Inventors: Prasun K. Chakravarty, William J. Greenlee, Nathan B. Mantlo, Arthur A. Patchett, Thomas F. Walsh
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Patent number: 5118689Abstract: A new piperidine compound is pharmacologically effective for treatment of arrythmia and has the formula: ##STR1## in which R.sup.1 is lower alkyl or tolyl; R.sup.2 is hydrogen, lower alkyl, lower alkenyl, cycloalkyl or cycloalkylalkyl; X is --CO--, --CH.sub.2 -- or --CHOH--; the sum of g plus h equals the integer 3 or 4 with g and h being 1, 2 or 3; A is substituted or unsubstituted alkylene, alkenylene, --(CH.sub.2).sub.k --S--, wherein k is an integer of 2 to 5, or --(CH.sub.2).sub.p CO--, wherein p is an integer of 1 to 4; and B is a compound having at least one heterocyclic ring containing a nitrogen atom.Type: GrantFiled: October 9, 1990Date of Patent: June 2, 1992Assignee: Eisai Co., Ltd.Inventors: Hitoshi Oinuma, Motosuke Yamanaka, Kazutoshi Miyake, Tomonori Hoshiko, Norio Minami, Tadao Shoji, Yoshiharu Daiku, Kohei Sawada, Kenichi Nomoto