Substituent On Ring Carbon Of The Bicyclo Ring System Contains The Additional Hetero Ring Patents (Class 548/467)
  • Patent number: 6750241
    Abstract: Disclosed are compounds which inhibit or modulate the activity of protein kinases and pharmaceutical compositions containing such compounds. The disclosed compound contain two or more ligand moieties covalently linked together by one or more linking groups. Such compounds are useful for treating diseases or medical disorders mediated by protein kinases.
    Type: Grant
    Filed: March 6, 2002
    Date of Patent: June 15, 2004
    Assignee: Theravance, Inc.
    Inventors: John H. Griffin, Yu-Hua Ji, Edmund J. Moran, Jonathan W. Wray
  • Patent number: 6743817
    Abstract: Disclosed are compounds of the formula and the pharmaceutically acceptable salts thereof wherein R, Ar, A, n, R1 and R2 are defined herein. These compounds are highly selective agonists, antagonists or inverse agonists for GABAA brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAA brain receptors and are therefore useful in the diagnosis and treatment of anxiety, depression, Down Syndrome, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory. Pharmaceutical compositions, including packaged pharmaceutical compositions, are also disclosed.
    Type: Grant
    Filed: September 6, 2001
    Date of Patent: June 1, 2004
    Assignee: Neurogen Corporation
    Inventors: George Maynard, LingHong Xie, Stanislaw Rachwal
  • Patent number: 6740649
    Abstract: The present application describes novel cyclic hydroxamic acids of formula I: or pharmaceutically acceptable salt forms thereof, wherein ring B is a 5-7 membered cyclic system containing from 0-2 heteroatoms selected from O, N, NR1, and S(O)p, and 0-1 carbonyl groups and the other variables are defined in the present specification, which are useful as inhibitors of matrix metalloproteinases (MMP), TNF-&agr; converting enzyme (TACE), aggrecanase or a combination thereof, pharmaceutical compositions containing the same, and methods of using the same.
    Type: Grant
    Filed: September 16, 2002
    Date of Patent: May 25, 2004
    Assignee: Bristol-Myers Squibb Company
    Inventors: Gregory R. Ott, Xiao-Tao Chen, Jingwu Duan, Zhonghui Lu
  • Patent number: 6740647
    Abstract: Novel five-membered heterocyclic amidines, their preparation and use as competitive inhibitors of trypsin-like serine proteases, especially thrombin and kininogenases such as kallikrein. Pharmaceutical compositions which contain the compounds as active ingredients, and use of the compounds as thrombin inhibitors, anticoagulants and antiinflammatory agents.
    Type: Grant
    Filed: June 21, 2000
    Date of Patent: May 25, 2004
    Assignee: Abbott GmbH & Co., KG
    Inventors: Dorit Baucke, Udo Lange, Helmut Mack, Werner Seitz, Hans Wolfgang Höffken, Wilfried Hornberger
  • Patent number: 6727266
    Abstract: A compound of the formula (I): wherein: R1 is represented by the formula: wherein R4, R5, R6, R7 and R8 are monovalent radicals such as: hydrogen, halogen, optionally substituted lower alkyl, lower alkyloxy, lower alkylthio, optionally substituted amino, nitro; non-aromatic heterocyclic group, and the like with certain provisos; Y is —OH or —NHOH; R2 is hydrogen, optionally substituted lower alkyl, or optionally substituted aralkyl; R3 is halogen, hydroxy, lower alkyloxy, or lower alkylthio; (b) n is an integer from 1 to 3; its optically active substance, its prodrug, its pharmaceutically acceptable salt, and its solvate.
    Type: Grant
    Filed: July 10, 2002
    Date of Patent: April 27, 2004
    Assignee: Shionogi & Co., Ltd.
    Inventor: Fumihiko Watanabe
  • Patent number: 6716870
    Abstract: The present invention is directed to prodrugs of certain 3-(pyrrol-2-yl-methylidene)-2-indolinone derivatives that modulate the activity of protein kinases (“PKs”). Pharmaceutical compositions comprising these compounds, methods of treating diseases related to abnormal PK activity utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.
    Type: Grant
    Filed: September 16, 2002
    Date of Patent: April 6, 2004
    Assignees: Sugen, Inc., Pharmacia & Upjohn Company
    Inventors: Malcolm Wilson Moon, Walter Morozowich, Ping Gao, Marcel Koenig
  • Patent number: 6706735
    Abstract: The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.
    Type: Grant
    Filed: June 26, 2002
    Date of Patent: March 16, 2004
    Assignee: Bristol-Myers Squibb Pharma Company
    Inventors: Paul S. Watson, Soo S. Ko, George V. DeLucca, John V. Duncia, Joseph B. Santella, III, Dean A. Wacker
  • Patent number: 6696574
    Abstract: The instant invention provides novel processes and intermediates useful in the preparation of certain N-(indole-2-carbonyl)-&bgr;-alaninamide compounds, which compounds are glycogen phosphorylase inhibitors useful in the treatment of diseases such as hypercholesterolemia, hyperglycemia, hyperinsulinemia, hyperlipidemia, hypertension, atherosclerosis, diabetes, diabetic cardiomyopathy, infection, tissue ischemia, myocardial ischemia, and in inhibiting tumor growth.
    Type: Grant
    Filed: January 16, 2003
    Date of Patent: February 24, 2004
    Assignee: Pfizer Inc.
    Inventors: Mark T. Barrila, Frank R. Busch, Michel A. Couturier, Susan L. Orrill, Peter R. Rose, Derek L. Tickner, Harry O. Tobiassen, Gregory J. Withbroe
  • Patent number: 6677367
    Abstract: A compound selected from the group consisting of a compound of formula I a compound of formula II and when the compound of formula I and II comprises an amino group pharmaceutically acceptable ammonium salts thereof, wherein R1, R2, Cx, n, R3, R4, R5, Y are as defined in the specification.
    Type: Grant
    Filed: October 24, 2002
    Date of Patent: January 13, 2004
    Assignee: Pharmacor Inc.
    Inventors: Brent Richard Stranix, Gilles Sauvé, Abderrahim Bouzide, Alexandre Coté, Gervais Bérubé, Patrick Soucy, Yongsen Zhao, Jocelyn Yelle
  • Patent number: 6673790
    Abstract: The present invention relates to novel indolin-2-one derivatives of formula: to the preparation and to the pharmaceutical compositions comprising them. These compounds have an affinity for oxytocin receptors.
    Type: Grant
    Filed: October 2, 2002
    Date of Patent: January 6, 2004
    Assignee: Sanofi-Synthelabo
    Inventors: Loïc Foulon, Georges Garcia, Claudine Serradeil-Le Gal, Gérard Valette
  • Patent number: 6653312
    Abstract: Amidine compounds of the formula wherein the substituents are defined as in the application useful as NO-synthase enzyme inhibitors.
    Type: Grant
    Filed: March 16, 2001
    Date of Patent: November 25, 2003
    Assignee: Societe de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S.)
    Inventors: Serge Auvin, Pierre-Etienne Chabrier de Lassauniere, Jeremiah Harnett, Dominique Pons, Gérard Ulibarri
  • Patent number: 6638964
    Abstract: The present invention creates a novel antiangiogenic agent and provides an antitumor agent which shows high safety as compared with conventional antitumor agents, has a sure effect and is able to be administered for a long period. That is, it provides an indole compound represented by the following formula (I), its pharmacologically acceptable salt or hydrates thereof: In the formula, R1 represents hydrogen atom, a halogen atom or cyano group; R2 and R3 are the same as or different from and each represents hydrogen atom, a C1˜C4 lower alkyl group or a halogen atom; R4 represents hydrogen atom or a C1˜C4 lower alkyl group; and the ring A represents cyanophenyl group, aminosulfonylphenyl group, aminopyridyl group, aminopyrimidyl group, a halopyridyl group or cyanothiophenyl group, provided that the case where all of R1, R2 and R3 are hydrogen atoms, where both R2 and R3 are hydrogen atoms or where the ring A is aminosulfonyl group and both R1 and R2 are halogen atoms is excluded.
    Type: Grant
    Filed: March 18, 2002
    Date of Patent: October 28, 2003
    Assignee: Eisai Co., Ltd.
    Inventors: Toru Haneda, Akihiko Tsuruoka, Junichi Kamata, Tadashi Okabe, Keiko Takahashi, Kazumasa Nara, Shinichi Hamaoka, Norihiro Ueda, Takashi Owa, Toshiaki Wakabayashi, Yasuhiro Funahashi, Taro Semba, Naoko Hata, Yuji Yamamoto, Yoichi Ozawa, Noako Tsukahara
  • Patent number: 6630503
    Abstract: A cell adhesion inhibitor of the general formula: R3—L—L′—R1 is disclosed. An inhibitor of the present invention interacts with VLA-4 molecules and inhibits VLA-4 dependent cell adhesion. Also disclosed are methods for preparing and using such a cell adhesion inhibitor, as well as pharmaceutical compositions containing the same.
    Type: Grant
    Filed: August 14, 2000
    Date of Patent: October 7, 2003
    Assignee: Biogen, Inc.
    Inventors: Daniel Scott, Wen-Cherng Lee, Russell C. Petter, Mark Cornebise
  • Patent number: 6576656
    Abstract: An oxindole of Formula 1 or a prodrug thereof, or a pharmaceutically acceptable salt thereof is useful for growth hormone releaser: wherein R1, R2, R3 and R4 are independently hydrogen, optionally substituted alkyl etc; R5 is optionally substituted aryl or optionally substituted heteroaryl; Z is —O— or —NH—; one of W1 and W2 is hydrogen, alkyl or —Y—CON(R10)R11; the other of W1 and W2 is n is 1, 2 or 3; m is 0, 1, 2 or 3; Y is single bond or C1-C3 alkylene; R6 and R7 are independently hydrogen, optionally substituted alkyl etc; R8 and R9 are independently hydrogen, optionally substituted alkyl etc; R10 and R11 are independently hydrogen, alkyl etc.
    Type: Grant
    Filed: March 22, 2001
    Date of Patent: June 10, 2003
    Assignee: Sumitomo Pharmaceuticals Co., Ltd.
    Inventors: Teruhisa Tokunaga, Takashi Umezome, W. Ewan Hume, Ryu Nagata, Kazuhiko Okazaki, Yasuyuki Ueki, Kazuo Kumagai
  • Publication number: 20030092756
    Abstract: The present invention relates to indolinones substituted in the 6-position of general formula 1
    Type: Application
    Filed: April 4, 2002
    Publication date: May 15, 2003
    Inventors: Gerald Juergen Roth, Armin Heckel, Thorsten Lehmann-Lintz, Joerg Kley, Frank Hilberg, Jacobus Van Meel
  • Patent number: 6545035
    Abstract: Substituted indolinones of general formula having effect on various kinases and cycline/CDK complexes and on the proliferation of various tumour cells. Exemplary compounds are: 3-Z-[1-(4-(N-Benzyl-N-methyl-aminomethyl)-phenylamino)-1-methyl-methylene]-5-amido-2-indolinone and 3-Z-[1-(4-(2,3,4,5-Tetrahydro-benzo(d)azepin-3-yl-methyl)-phenylamino)-1-methyl-methylene]-5-amido-2-indolinone.
    Type: Grant
    Filed: October 3, 2001
    Date of Patent: April 8, 2003
    Assignee: Boehringer Ingelheim Pharma KG
    Inventors: Armin Heckel, Rainer Walter, Wolfgang Grell, Jacobus C. A. Van Meel, Norbert Redemann
  • Patent number: 6531474
    Abstract: The present invention relates to novel classes of compounds which are caspase inhibitors, in particular interleukin-1&bgr; converting enzyme (“ICE”) inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase activity and consequently, may be advantageously used as agents against interleukin-1-(“IL-1”), apoptosis-, interferon-&ggr; inducing factor-(IGIF), or interferon-&ggr;-(“IFN-&ggr;”) mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases.
    Type: Grant
    Filed: September 19, 2000
    Date of Patent: March 11, 2003
    Assignee: Vertex Pharmaceuticals Incorporated
    Inventors: Marion W. Wannamaker, Guy W. Bemis, Paul S. Charifson, David J. Lauffer, Michael D. Mullican, Mark A. Murcko, Keith P. Wilson, James W. Janetka, Robert J. Davies, Anne-Laure Grillot, Zhan Shi, Cornelia J. Forster
  • Publication number: 20030045565
    Abstract: The present invention is directed to 1-pyrrolidin-1-ylmethyl-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives that modulate the activity of protein kinases (“PKs”). Pharmaceutical compositions comprising these compounds, methods of treating diseases related to abnormal PK activity utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.
    Type: Application
    Filed: September 16, 2002
    Publication date: March 6, 2003
    Applicant: Pharmacia & Upjohn Company
    Inventors: Malcolm Wilson Moon, Walter Morozowich, Ping Gao
  • Patent number: 6514970
    Abstract: The present invention relates to pyrrolidiones, pharmaceutical compostions containing them and their use as antagonist of urotensin II.
    Type: Grant
    Filed: June 13, 2002
    Date of Patent: February 4, 2003
    Assignee: SmithKline Beecham Corporation
    Inventors: Dashyant Dhanak, Steven David Knight, Gregory Lee Warren, Jian Jin, Katherine L. Widdowson, Richard McCulloch Keenan
  • Patent number: 6503907
    Abstract: The present invention relates to indole derivatives, dihydroindole derivatives and pharmaceutically acceptable salts and/or pharmaceutically acceptable esters thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with 2,3-oxidosqualene-lanosterol cyclase such as hypercholesterolemia, hyperlipemia, arteriosclerosis, vascular diseases, mycoses, gallstones, tumors and/or hyperproliferative disorders, and treatment and/or prophylaxis of impaired glucose tolerance and diabetes.
    Type: Grant
    Filed: November 20, 2001
    Date of Patent: January 7, 2003
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Jean Ackermann, Johannes Aebi, Henrietta Dehmlow, Olivier Morand, Narendra Panday, Thomas Weller
  • Patent number: 6495719
    Abstract: Compounds having a zinc-binding moiety, such as, for example, a hydroxamic acid group, can inhibit histone deacetylase. Histone deacetylase inhibition can repress gene expression, including expression of genes related to tumor suppression. Inhibition of histone deacetylase can lead to the histone deacetylase-mediated transcriptional repression of tumor suppressor genes. For example, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, such as hematopoiesis, and genetic related metabolic disorders, such as, cystic fibrosis and adrenoleukodystrophy.
    Type: Grant
    Filed: March 27, 2001
    Date of Patent: December 17, 2002
    Assignee: CircaGen Pharmaceutical
    Inventors: Hsuan-Yin Lan-Hargest, Robert J. Kaufman, Norbert L. Wiech
  • Patent number: 6492374
    Abstract: The present invention relates to benzofuran derivatives having general Formula (I) wherein A is selected from (1), (2), (3), (4) wherein Z is O or S; s is 0 or 1; q is 0 or 1; R4 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C26-alkynyl, C1-6-alkyl-aryl, or C1-6-alkyl-O-aryl; D is a spacer group selected from branched or straight chain C1-6-alkylene, C2-6-alkenylene and C2-6-alkynylene; its enantiomers, and pharmaceutically acceptable acid addition salt thereof. The compounds are potently binding to the 5-HT1A receptor.
    Type: Grant
    Filed: June 4, 2001
    Date of Patent: December 10, 2002
    Assignee: H. Lundbeck A/S
    Inventors: Kim Andersen, Mario Rottländer, Klaus Peter Bøgesø, Henrik Pedersen, Thomas Ruhland, Robert Dancer
  • Patent number: 6486153
    Abstract: A class of tryptamine analogues bearing an optionally substituted phenyl nucleus at the 2-position are selective antagonists of the human 5-HT2A receptor and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of adverse neurological conditions, including psychotic disorders such as schizophrenia.
    Type: Grant
    Filed: March 3, 2000
    Date of Patent: November 26, 2002
    Assignee: Merck Sharp & Dohme Ltd.
    Inventors: Jose Luis Castro Pineiro, Steven Michael Hutchins, Stephen John Lewis, Michael Rowley, Adrian Leonard Smith, Graeme Irvine Stevenson
  • Patent number: 6482848
    Abstract: The present invention is directed to prodrugs of certain 3-(pyrrol-2-yl-methylidene)-2-indolinone derivatives that modulate the activity of protein kinases (“PKs”). Pharmaceutical compositions comprising these compounds, methods of treating diseases related to abnormal PK activity utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.
    Type: Grant
    Filed: May 24, 2001
    Date of Patent: November 19, 2002
    Assignee: Sugen Incorporated
    Inventors: Malcolm Wilson Moon, Walter Morozowich, Ping Gao, Marcel Koenig
  • Patent number: 6472418
    Abstract: Non-peptide acetamide derivatives of Formula I are specific NK1 antagonist, where R is aryl, R1 and R2 are H or alkyl, m, n and q are integers from 0 to 4, X is NR8 or NHCONH, R3 and R9 are H or alkyl, R4 is naphthyl or indolyl, R5 and R2 are H or alkyl, and R6 is aryl. The compounds are useful agents for treating inflammatory and allergic disorders, pain, anxiety, depression, schizophrenia and emesis.
    Type: Grant
    Filed: June 18, 2001
    Date of Patent: October 29, 2002
    Assignee: Warner-Lambert Company
    Inventors: Mark Wallace Creswell, Michael Higginbottom, David Christopher Horwell, Russel Andrew Lewthwaite, Martyn Clive Pritchard, Jennifer Raphy
  • Patent number: 6469043
    Abstract: The present invention creates a novel antiangiogenic agent and provides an antitumor agent which shows high safety as compared with conventional antitumor agents, has a sure effect and is able to be administered for a long period. That is, it provides an indole compound represented by the following formula (I), its pharmacologically acceptable salt or hydrates thereof. In the formula, R1 represents hydrogen atom, a halogen atom or cyano group; R2 and R3 are the same as or different from and each represents hydrogen atom, a C1˜C4 lower alkyl group or a halogen atom; R4 represents hydrogen atom or a C1˜C4 lower alkyl group; and the ring A represents cyanophenyl group, aminosulfonylphenyl group, aminopyridyl group, aminopyrimidyl group, a halopyridyl group or cyanothiophenyl group, provided that the case where all of R1, R2 and R3 are hydrogen atoms, where both R2 and R3 are hydrogen atoms or where the ring A is aminosulfonyl group and both R1 and R2 are halogen atoms is excluded.
    Type: Grant
    Filed: September 28, 2000
    Date of Patent: October 22, 2002
    Assignee: Eisai Co., Ltd.
    Inventors: Toru Haneda, Akihiko Tsuruoka, Junichi Kamata, Tadashi Okabe, Keiko Takahashi, Kazumasa Nara, Shinichi Hamaoka, Norihiro Ueda, Takashi Owa, Toshiaki Wakabayashi, Yasuhiro Funahashi, Taro Semba, Naoko Hata, Yuji Yamamoto, Yoichi Ozawa, Noako Tsukahara
  • Patent number: 6409956
    Abstract: An injection-molding process using warp-free pigment compositions including diaryldiketopyrrolo[3,4-C]pyrroles to improve the dimensional stability of the injection molded product by decreasing warping wherein the constituents of the formulation being injection molded are added into an injection molding machine in ready-premixed form or simultaneously as individual components. Preferred pigments are quinacridone pigments, disazo condensation pigments, isoindolinone pigments and pyrrolo[3,4-C]pyrrole pigments with pyrrolo[3,4-C]pyrrole pigments being especially preferred.
    Type: Grant
    Filed: April 20, 1999
    Date of Patent: June 25, 2002
    Assignee: Ciba Specialty Chemicals Corporation
    Inventors: Franck Rey Flandrin, Guo-Hua Hu, Philippe Bugnon, Zhimin Hao
  • Patent number: 6403792
    Abstract: The present invention is to novel sulfonyl isatin compounds of Formula (I), their pharmaceutical compositions, and the novel inhibition of caspases for use in the treatment of apoptosis, and disease states caused by excessive or inappropriate cell death.
    Type: Grant
    Filed: December 9, 1999
    Date of Patent: June 11, 2002
    Assignee: SmithKline Beecham Corporation
    Inventors: Dennis Lee, Scott Allen Long
  • Patent number: 6395766
    Abstract: Compounds according to Formula (I) or a pharmaceutically acceptable salt thereof are GABA-A Alpha 5 ligands useful for enhancing cognition: where A is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, arylC1-6alkyl, or aryl wherein the aryl group is optionally substituted by halogen, C1-6alkyl, CF3, CN, NO2 or NH2, NR1R10, S(O)pR1, heteroarylC1-6alkyl or heteroaryl where heteroaryl is a 5- or 6-membered heteroaromatic ring as defined for B; and B is phenyl or a 5-membered ring having one or two unsaturations containing 1, 2, 3, or 4 heteroatoms chosen from O, N and S provided that not more than one heteroatom is other than N, a 6-membered heteroaromatic ring containing 1, 2, 3 or 4 nitrogen atoms, each of which rings is optionally substituted by one or more substituents.
    Type: Grant
    Filed: November 6, 2000
    Date of Patent: May 28, 2002
    Assignee: Merck Sharp & Dohme Limited
    Inventors: Howard Barff Broughton, Helen Jane Bryant, Mark Stuart Chambers, Neil Roy Curtis
  • Patent number: 6346621
    Abstract: A nitrogen-heterocyclic compound is provided which is represented by General Formula (1): where R1 and R2 are independently hydrogen, an alkyl group, an aryl group, or a heteroaryl group; R3 is hydrogen or an aryl group; R4 is a substituted amino group, an alkoxy group, a nitro group, or halogen; m is an integer from 0 to 2; and n is 0 or 1. A process for producing the above compound is also provided. This compound is useful as a source material of medicines, pesticides, electronic materials, and intermediates for other substituted nitrogen-heterocyclic compounds.
    Type: Grant
    Filed: March 10, 2000
    Date of Patent: February 12, 2002
    Assignee: Tosoh Corporation
    Inventors: Makoto Watanabe, Toshihide Yamamoto, Masakazu Nishiyama
  • Patent number: 6313164
    Abstract: Compounds of the formula (I): wherein one of m and n is 0, and the other is 0, 1 or 2; k is 0 or 1 to 12; R1 is hydrogen, a substituent which is an aryl or a heterocyclic, or an optionally substituted alkyl group; A is a single bond, an oxygen atom, a carbonyl group or a group of the formula —N(R2)CO—, —N(R2)CS—, —N(R2)SO2—, —CON(R2)N(R3)CO—, —CON(R2)CO—, —CON(R2)CS—, —CON(R2)SO2—, —O—CO—, —ON(R2)CO—, —ON(R2)SO2—, —O—CON(R2)N(R3)CO—, —O—CON(R2)CO—, —O—CON(R2)SO2—, —CO—O—, —CO—CO—, —CO—CON(R2)N(R3)CO—, —CO—CON(R2)CO—, —CO—CON(R2)SO2—, —N(R2)O—, —N(R2)COCO—, —N(R2)N(R3)CO—, —N(R2)N(R3)SO2—, —N(R2)CON(R3)N(R4)CO—, —N(R2)CON(R3)CO—, —N(R2)CON(R3)SO2&mdas
    Type: Grant
    Filed: July 15, 1999
    Date of Patent: November 6, 2001
    Assignee: Sankyo Company, Limited
    Inventors: Takashi Fujita, Tomihisa Yokoyama
  • Patent number: 6303620
    Abstract: Disclosed are 4,4-disubstituted and 3,3-disubstituted piperidine compounds of formula I wherein D, E, G, J, R1, a, b, c, and d are defined in the specification, compositions containing them, and their use for treating medical disorders resulting from a deficiency in growth hormone.
    Type: Grant
    Filed: May 6, 1999
    Date of Patent: October 16, 2001
    Assignee: Novo Nordisk A/S
    Inventors: Thomas Kruse Hansen, Michael Ankersen
  • Patent number: 6291683
    Abstract: Compounds useful for alleviating symptoms of depression are provided which have the following formula: wherein: R1 is hydrogen, lower alkyl or aryl; R2 is hydrogen, lower alkyl, phenyl or substituted phenyl; X and Y are each, independently, hydrogen, lower alkyl, lower alkoxy, or halogen, or together combine with the carbon atoms to which they are attached to complete a cyclopentyl, cyclohexyl, phenyl, pyrrolyl, pyranyl, pyridinyl, dihydrofuranyl, furanyl, dioxanyl, oxazolyl or isoxazolyl group; Z is hydrogen, halogen or lower alkoxy; with the proviso that when X, Y or Z represent lower alkoxy, they are not present at the ortho position; W is hydrogen, halogen, lower alkyl, cyano or a trifluoromethyl group; and n is 2-5; or pharmaceutically acceptable salts thereof.
    Type: Grant
    Filed: June 13, 2000
    Date of Patent: September 18, 2001
    Assignee: American Home Products Corp
    Inventors: Richard E. Mewshaw, Dahui Zhou
  • Patent number: 6245799
    Abstract: This invention provides novel compounds and pharmaceutical compositions and methods of using the compounds in the treatment of central nervous system disorders, such as anxiety and depression, the compounds having the formula I: wherein: X is N—R, O, S(O)m; m is 0 to 2; n is 0 to 4; Ar is an aryl group of 6 to 12 carbon atoms optionally substituted with 1 to 3 R3 groups, or a heteroaryl group of 4 to 10 carbon atoms optionally substituted with 1 to 3 R3 groups; R and R2 are independently H, straight chain alkyl of 1 to 6 carbon atoms, branched alkyl of 3 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms, alkylcarbonyl of 1 to 6 carbon atoms, aminocarbonyl, or alkylaminocarbonyl of 1 to 4 carbon atoms; R1 and R3 are independently H, straight chain alkyl of 1 to 4 carbon atoms, branched alkyl of 3 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, halo, alkoxy group of 1 to 4 carbon atoms, haloalkyl of 1 to 4 carbon atoms, OH, nitro, amino,
    Type: Grant
    Filed: November 6, 2000
    Date of Patent: June 12, 2001
    Assignee: American Home Products Corp
    Inventors: Magda Asselin, John W. Ellingboe, Richard E. Mewshaw
  • Patent number: 6242438
    Abstract: The present invention provides compounds of formula (I) and the pharmaceutically acceptable salts thereof. Such compounds and salts are tachykinin antagonists.
    Type: Grant
    Filed: June 1, 1998
    Date of Patent: June 5, 2001
    Assignee: Pfizer Inc.
    Inventors: Alexander Roderick MacKenzie, Allan Patrick Marchington, Donald Stuart Middleton, Sandra Dora Meadows
  • Patent number: 6235768
    Abstract: Compounds having a metalloproteinase inhibitory activity, represented by the formula (I), its optically active isomers, their pharmaceutically acceptable salts, or hydrates thereof.
    Type: Grant
    Filed: May 10, 1999
    Date of Patent: May 22, 2001
    Assignee: Shionogi & Co., Ltd.
    Inventors: Fumihiko Wantanabe, Hiroshige Tsuzuki, Mitsuaki Ohtani
  • Patent number: 6232468
    Abstract: Disclosed are compounds which are neurokinin (tachykinin)-antagonists, useful for the treatment or prevention of inflammatory and allergic disease.
    Type: Grant
    Filed: December 1, 1999
    Date of Patent: May 15, 2001
    Assignee: Boehringer Ingelheim KG
    Inventors: Franz Esser, Gerd Schnorrenberg, Hans-Peter Ignatow, Günther Giesler, Birgit Jung, Georg Speck
  • Patent number: 6228872
    Abstract: The present invention relates to the design, synthesis, and the peptidyl-prolyl isomerase (PPIase or rotamase) inhibitory activity of novel pyrrolidinemethyl diamide and carbamate compounds that are neurotrophic agents (i.e. compounds capable of stimulating growth or proliferation of nervous tissue) and that bind to immunophilins such as FKBP12 and inhibit their rotamase activity. This invention also relates to pharmaceutical compositions comprising these compounds.
    Type: Grant
    Filed: November 8, 1999
    Date of Patent: May 8, 2001
    Assignee: Bristol-Myers Squibb Company
    Inventors: Gene M. Dubowchik, Jonathan L. Ditta, David P. Provencal, Derek J. Denhart
  • Patent number: 6207686
    Abstract: A compound of formula (I), in which: R1 is lower alkyl, cyclo(lower)alkyl, optionally substituted aryl, optionally substituted heterocyclic group, cyclo(lower)alkyl(lower)alkyl, or ar(lower)alkyl; R2 is hydrogen, hydroxy or protected hydroxy; R3 is lower alkyl, aryl, ar(lower)alkyl or optionally substituted heterocyclic(lower)alkyl; R4 is carboxy, protected carboxy or lower alkylsufonylcarbamoyl; R5 is hydrogen or lower alkyl; R6 is hydrogen or heterocyclic group; A is a single bond or lower alkylene, and Ar is optionally substituted aryl, or pharmaceutically acceptable salts thereof, having endothelin antagonistic activity.
    Type: Grant
    Filed: June 20, 1997
    Date of Patent: March 27, 2001
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Masahiro Neya, Tatsuya Zenkoh, Hitoshi Sawada, Chiyoshi Kasahara, Masayoshi Murata, Keiji Hemmi
  • Patent number: 6207698
    Abstract: Compounds having a metalloproteinase inhibitory activity, represented by the formula (I), its optically active isomers, their pharmaceutically acceptable salts, or hydrates thereof.
    Type: Grant
    Filed: July 22, 1998
    Date of Patent: March 27, 2001
    Assignee: Shionogi & Co., Ltd.
    Inventors: Fumihiko Wantanabe, Hiroshige Tsuzuki, Mitsuaki Ohtani
  • Patent number: 6187805
    Abstract: Three classes of indole and indoline derivatives are disclosed as ligands selective for the 5-HT6 receptors, and hence of value in the treatment or prevention of CNS disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, depression and anxiety. A particular class, 1-substituted-4-(&ohgr;-N,N-dialkyl-aminoalkyl)indoles, are claimed as novel compounds.
    Type: Grant
    Filed: September 9, 1999
    Date of Patent: February 13, 2001
    Assignee: Merck Sharp & Dohme Ltd.
    Inventors: Jose Luis Castro Pineiro, George Mc Allister, Michael Geoffrey Neil Russel
  • Patent number: 6172100
    Abstract: This application relates to the use as thrombin inhibitors, coagulation inhibitors and thromboembolic disorder agents of heterocyclic derivatives of formula (I) as defined herein. It also provides novel compounds of formula (I), processes and intermediates for their preparation, and pharmaceutical formulations comprising the novel compounds of formula (I).
    Type: Grant
    Filed: December 21, 1999
    Date of Patent: January 9, 2001
    Assignee: Eli Lilly and Company
    Inventors: Nickolay Y Chirgadze, Matthew J Fisher, Richard W Harper, Ho-Shen Lin, Jefferson R McCowan, Daniel J Sall, Gerald F Smith, Kumiko Takeuchi, Michael R Wiley, Minsheng Zhang
  • Patent number: 6156772
    Abstract: There are disclosed compounds of formula (I) ##STR1## and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related and other conditions in both men and women.
    Type: Grant
    Filed: May 14, 1999
    Date of Patent: December 5, 2000
    Assignee: Merck & Co., Inc.
    Inventors: Mark Goulet, Thomas F. Walsh, Feroze Ujjainwalla, Matthew J. Wyvratt, Jr.
  • Patent number: 6153642
    Abstract: Benzoheterocyclic distamycin derivatives of formula (I) wherein: n is 2, 3 or 4; A is O, S, or NR, wherein R is hydrogen or C.sub.1 -C.sub.4 alkyl; B is CH or N; R.sub.1 is hydrogen or C.sub.1 -C.sub.4 alkyl; T is selected from; (i) formula (II) wherein: p is zero or 1; R.sub.2 and R.sub.3 are selected, each independently, from: hydrogen, C.sub.1 -C.sub.4 alkyl optionally substituted by one or more fluorine atoms, and C.sub.1 -C.sub.4 alkoxy; R.sub.4 is C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.3 haloalkyl; X.sub.1 is a halogen atom; and (ii) formula (III) wherein X.sub.2 is a halogen atom; and pharmaceutically acceptable salts thereof, are described. Such compounds are useful as antineoplastic and antiviral agents.
    Type: Grant
    Filed: May 4, 1999
    Date of Patent: November 28, 2000
    Assignee: Pharmacia & Upjohn S.p.A.
    Inventors: Paolo Cozzi, Pier Giovanni Baraldi, Italo Beria, Marina Caldarelli, Laura Capolongo, Giampiero Spalluto, Romeo Romagnoli
  • Patent number: 6120987
    Abstract: The invention relates to a process for the preparation of a fluorescent conjugate between a carrier molecule possessing at least one amino, hydroxyl, carboxyl and/or sulfhydryl group and a fluorophoric reagent possessing at least one functional group capable of reacting with said amino, hydroxyl, carboxyl and/or sulfhydryl group(s), which consists in bringing said carrier molecule and said fluorophoric reagent into contact with an aqueous solution of a water-soluble macrocycle.The invention further relates to the conjugates obtained by this process and to their use.
    Type: Grant
    Filed: June 10, 1998
    Date of Patent: September 19, 2000
    Assignee: Cis bio International
    Inventor: Daniel Aspe
  • Patent number: 6117893
    Abstract: Compound of formula (I): ##STR1## [wherein: X represents an unsubstituted or substituted indolyl, indolinyl, azaindolyl, azaindolinyl, imidazopyridyl or imidazopyrimidinyl group; Y represents an oxygen or sulphur atom; Z represents a 2,4-dioxothiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxooxadiazolidin-2-ylmethyl or N-hydroxyureidomethyl group; R represents a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, a hydroxy group, a nitro group, an aralkyl group or a unsubstituted or substituted amino group; and m is an integer of from 1 to 5] have hypoglycemic and anti-diabetic activities.
    Type: Grant
    Filed: March 3, 1999
    Date of Patent: September 12, 2000
    Assignee: Sankyo Company, Limited
    Inventors: Takashi Fujita, Takao Yoshioka, Toshihiko Fujiwara, Minoru Oguchi, Hiroaki Yanagisawa, Hiroyoshi Horikoshi, Kunio Wada, Koichi Fujimoto
  • Patent number: 6096887
    Abstract: The present invention encompasses structures of the formula I: ##STR1## or the pharmaceutically acceptable non-toxic salts thereof wherein: ##STR2## W represents substituted or unsubstituted heteroaryl; X is hydrogen, hydroxy or lower alkyl;T is hydrogen, halogen, hydroxy, nitro, amino or alkyl;R.sub.3 is hydrogen or an organic group;R.sub.4 is hydrogen or substituted or unsubstituted organic substituent;R.sub.5 and R.sub.6 represent organic, and inorganic substituents; and n is 1,2,3, or 4,which compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAa brain receptors. These compounds are useful in the diagnosis and treatment of anxiety, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory.
    Type: Grant
    Filed: February 25, 1998
    Date of Patent: August 1, 2000
    Assignee: Neurogen Corporation
    Inventors: Pamela Albaugh, Gang Liu, Alan Hutchison
  • Patent number: 6025494
    Abstract: A compound of formula (I) ##STR1## and salts and solvates thereof, in which: R.sup.0 represents hydrogen, halogen or C.sub.1-6 alkyl;R.sup.1 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, haloC.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkylC.sub.1-3 alkyl, arylC.sub.1-3 alkyl or heteroarylC.sub.1-3 alkyl;R.sup.2 represents an optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan and pyridine or an optionally substituted bicyclic ring ##STR2## attached to the rest of the molecule via one of the benzene ring carbon atoms and wherein the fused ring A is a 5- or 6-membered ring which may be saturated or partially or fully unsaturated and comprises carbon atoms and optionally one or two heteroatoms selected from oxygen, sulphur and nitrogen; andR.sup.3 represents hydrogen or C.sub.1-3 alkyl, or R.sup.1 and R.sup.3 together represent a 3- or 4-membered alkyl or alkenyl chain.
    Type: Grant
    Filed: August 12, 1998
    Date of Patent: February 15, 2000
    Assignee: ICOS Corporation
    Inventor: Alain Claude-Marie Daugan
  • Patent number: 6013663
    Abstract: A compound of formula (I): ##STR1## wherein one of m and n represents 0, and the other represents 0, 1 or 2; k represents 0 or 1 to 12; R.sup.1 is hydrogen, an aryl, a heterocyclic, an alkyl, a hydroxy or --OR.sup.7, wherein R.sup.7 is an alkyl, an alkenyl or an aralkyl; A is --CON(R.sup.2)SO.sub.2--, wherein R.sup.2 is hydrogen, an alkyl or an aralkyl; B is a single bond; and pharmaceutically acceptable salts thereof. The compounds have the ability to enhance the activity of glutathione reductase and can therefore be used for the treatment and prevention of a variety of diseases including cataracts.
    Type: Grant
    Filed: March 31, 1998
    Date of Patent: January 11, 2000
    Assignee: Sankyo Company, Limited
    Inventors: Takashi Fujita, Tomihisa Yokoyama
  • Patent number: 6013777
    Abstract: Compounds of formulaA(B).sub.x, (I),wherein x is an integer from 1 to 4,A is the radical of a chromophore of the quinacridone, anthraquinone, perylene, indigo, quinophthalone, isoindolinone, isoindoline, dioxazine, phthalocyanine or azo series, which radical contains x N-atoms attached to B, preferably with at least one directly adjacent or conjugated carbonyl group,B is a group of formula ##STR1## and, if x is 2, 3 or 4, may also be one, two or three hydrogen atoms. The symbols Q, R.sub.1, R.sub.2, R.sub.3, R.sub.4, X, Y, Z, m and n, are as defined in claim 1.These carbamate group-containing soluble chromophores are distinguished by outstanding solid state fluorescence in the UV range as well as the by ease with which they can be converted to the corresponding pigments in the substrate in which they are incorporated.
    Type: Grant
    Filed: June 10, 1998
    Date of Patent: January 11, 2000
    Assignee: Ciba Specialty Chemicals Corporation
    Inventors: Zhimin Hao, John S. Zambounis, Abul Iqbal