The Additional Hetero Ring Is Bonded Directly To A Ring Carbon Of The Bicyclo Ring System Patents (Class 548/466)
  • Patent number: 6521657
    Abstract: This invention relates to compounds which are agonists of the progesterone receptor which have the general structure: wherein: R1, R2, R3, R4, R5 and Q1 are as defined herein, or a pharmaceutically acceptable salt thereof, as well as methods of using these compounds to induce contraception or treat progesterone-related carcinomas and adenocarcinomas.
    Type: Grant
    Filed: October 30, 2001
    Date of Patent: February 18, 2003
    Assignees: Wyeth, Ligand Pharmaceuticals, Inc.
    Inventors: Andrew Fensome, Puwen Zhang, Marci C. Koko, Lin Zhi, Todd K. Jones, Jay E. Wrobel, Christopher M. Tegley, James P. Edwards, Edward G. Melenski
  • Patent number: 6518429
    Abstract: The present invention relates to novel imidazole derivatives which show an inhibitory activity against farnesyl transferase, pharmaceutically acceptable salts or isomers thereof and pharmaceutical compositions comprising such imidazole derivatives. More particularly, the present invention relates to intermediate compounds which are used in the preparation of the imidazole derivatives of the invention. Related processes also are disclosed.
    Type: Grant
    Filed: March 20, 2001
    Date of Patent: February 11, 2003
    Assignee: LG Chemical, Ltd.
    Inventors: Hyun Il Lee, Jong Sung Koh, Jin Ho Lee, Won Hee Jung, You Seung Shin, Hyun Ho Chung, Jong Hyun Kim, Seong Gu Ro, Tae Saeng Choi, Shin Wu Jeong, Tae Hwan Kwak, In Ae Ahn, Hyun Sung Kim, Sun Hwa Lee, Kwi Hwa Kim, Jung Kwon Yoo
  • 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: 6479490
    Abstract: This invention relates to inhibitors of glycogen synthase kinase-3&bgr;, methods of treating diseases characterized by an excess of Th2 cytokines, and to 3-indolyl-4-phenyl-1H-pyrrole-2,5-dione derivatives of Formula (I): that are inhibitors of glycogen synthase kinase -3&bgr;, pharmaceutical compositions containing them, methods for their use and methods for preparing these compounds.
    Type: Grant
    Filed: July 27, 2001
    Date of Patent: November 12, 2002
    Assignee: Syntex (U.S.A.) LLC
    Inventors: Leyi Gong, Andrew Grupe, Gary Allen Peltz
  • Patent number: 6444615
    Abstract: This invention relates to 1-substituted-phenyl-3-substituted-2-thioxo-4,5-imidazolidinediones and 2,4,5-imidazolidinetriones which have activity as herbicides, to compositions which contain these compounds and to methods of use of these compounds. In particular, the present invention pertains to 2-thioxo-4,5-imidazolidinediones or 2,4,5-imidazolidinetriones wherein a 2,4,5,6-tetrasubstituted phenyl ring is linked to the heterocyclic ring.
    Type: Grant
    Filed: April 18, 2000
    Date of Patent: September 3, 2002
    Assignee: Dow AgroSciences LLC
    Inventors: Bin Li, Ying Man, Zongjian Zhang, Adam Chi-Tung Hsu
  • 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: 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
  • Publication number: 20020058817
    Abstract: The present invention provides convergent processes for preparing epothilones, desoxyepothilones, and analogues thereof. The present invention further provides novel compositions and methods for the treatment of cancer and additionally provides methods for the treatment of cancer which has developed a multi-drug phenotype.
    Type: Application
    Filed: March 1, 2001
    Publication date: May 16, 2002
    Inventors: Samuel J. Danishefsky, Shawn J. Stachel, Chul Bom Lee, Mark D. Chappell, Zhicai Wu
  • Patent number: 6387923
    Abstract: Compounds represented by the formula: wherein A is selected from the group consisting of W is NH2 or H; and each X, Y and Z is individually selected from the group consisting of OH, H and halogen provided at least one of X and Y is H; tautomers, or pharmaceutically acceptable salts thereof; are provided. Compounds of the present invention are useful as inhibitors of PNP and of T-cell proliferation. Compounds of the present invention are useful for treating Cancer. Method for preparing the compounds of the present invention are also provided.
    Type: Grant
    Filed: March 22, 2001
    Date of Patent: May 14, 2002
    Assignee: Biocryst Pharmacueticals, Inc.
    Inventors: Philip E. Morris, Jr., John A. Montgomery, Yarlagadda S. Babu
  • Publication number: 20020052397
    Abstract: This invention relates to inhibitors of glycogen synthase kinase-3&bgr;, methods of treating diseases characterized by an excess of Th2 cytokines, and to 3-indolyl-4-phenyl-1H-pyrrole-2,5-dione derivatives of Formula (I): 1
    Type: Application
    Filed: July 27, 2001
    Publication date: May 2, 2002
    Inventors: Leyi Gong, Andrew Grupe, Gary Allen Peltz
  • Patent number: 6358993
    Abstract: The present invention relates to pharmaceutically acceptable compounds, including certain substituted indolinyl and derivatives thereof, 1,2,3,4-tetrahydroquinolinyl and derivatives thereof, 1,2,3,4-tetrahydroisoquinolinyl, benz[cd]indolinyl and 5,6-dihydrophenanthridinyl compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are particularly useful for the treatment or prophylaxis of neurological injury and neurodegenerative disorders.
    Type: Grant
    Filed: October 22, 1999
    Date of Patent: March 19, 2002
    Assignee: CeNes Pharmaceuticals, Inc.
    Inventors: N. Laxma Reddy, Michael Maillard, David Berlove, Sharad Magar, Graham J. Durant
  • Patent number: 6353008
    Abstract: The present invention provides the compounds of the following formula (I): and a method for inhibiting the reuptake of seretonin, antagonizing the 5-HT1A receptor and antagonizing the 5-HT2A receptor which comprises administering to a subject in need of such treatment an effective amount of formula (I).
    Type: Grant
    Filed: November 28, 2000
    Date of Patent: March 5, 2002
    Assignee: Eli Lilly and Company
    Inventors: Larry Wayne Hertel, Yao-Chang Xu
  • Patent number: 6344468
    Abstract: The present invention relates to substituted isoindolone derivatives of the formula I, in which R1, R2, R3, R4, R5, R6 and R7 are as defined in the claims, which are useful pharmaceutically active compounds for the therapy and prophylaxis of illnesses, for example cardiovascular diseases such as hypertension, angina pectoris, cardiac insufficiency, thromboses or atherosclerosis. The compounds of the formula I are capable of modulating the body's production of cyclic guanosine monophosphate (cGMP) and are generally suitable for the therapy and prophylaxis of illnesses which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of the formula I, to their use for the therapy and prophylaxis of the abovementioned illnesses and for preparing pharmaceuticals for these, and also pharmaceutical preparations which comprise compounds of the formula I.
    Type: Grant
    Filed: October 6, 2000
    Date of Patent: February 5, 2002
    Assignee: Aventis Pharma Deutschland GmbH
    Inventors: Ursula Schindler, Karl Schoenafinger, Hartmut Strobel, Viola Groehn
  • Patent number: 6307056
    Abstract: Disclosed are 4-aryloxindoles that inhibit or modulate protein kinases, in particular JNK protein kinases. These compounds and their pharmaceutically acceptable salts, and prodrugs of said compounds, are useful as anti-inflammatory agents, particularly useful in the treatment of rheumatoid arthritis. Also disclosed are pharmaceutical compositions containing the foregoing compounds, as well as methods for the treatment and/or control of inflammation, particularly in the treatment or control of rheumatoid arthritis, using said compounds.
    Type: Grant
    Filed: December 15, 1999
    Date of Patent: October 23, 2001
    Assignee: Hoffman-La Roche Inc.
    Inventors: Wendy Lea Corbett, Kin-Chun Luk, Paige E. Mahaney
  • Patent number: 6268391
    Abstract: Compounds of general formula (I) wherein: R1 is H or optionally joined with R2 to form a fused ring selected from the group consisting of five to ten membered aryl, heteroaryl or heterocyclyl rings, R2 and R3 are independently H, HET, aryl, C1-12 aliphatic, CN, NO2, halogen, R10, —OR10, —SR10, —S(O)R10, —SO2R10, —NR10R11, —NR11R12, —NR12COR11, —NR12CO2R11, —NR12CONR11R12, —NO12SO2R11, —NR12C(NR 12)NHR11, —COR11, —CO2R11, —CONR12R11, —SO2NR12R11, —OCONR12R11, C(NR12)NR12R11, R6 and R7 are independently halogen, CN, NO2, —CONR10R11, —SO2NR10R11, —NR10R11, or —OR11, where R10 and R11 are as defined below; R8 is OH, NHSO2R12 or NHCOCF3; and their use in therapy, especially in the treatment of disorders mediated by cRaf1 kinase.
    Type: Grant
    Filed: April 7, 2000
    Date of Patent: July 31, 2001
    Assignee: Glaxo Wellcome Inc.
    Inventors: Scott Howard Dickerson, Philip Anthony Harris, Robert Neil Hunter, III, David Kendall Jung, Karen Elizabeth Lackey, Robert Walton McNutt, Jr., Michael Robert Peel, James Marvin Veal
  • Patent number: 6255306
    Abstract: The present invention relates to compounds of the formula
    Type: Grant
    Filed: August 11, 1998
    Date of Patent: July 3, 2001
    Inventor: John E. Macor
  • 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: 6180643
    Abstract: The present invention comprises a new class of novel aryl and heteroaryl substituted fused pyrrole compounds useful for the prophylaxis and treatment of diseases or conditions, such as TNF-&agr;, IL-1&bgr;, IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. In particular, the compounds of the invention are useful for the prophylaxis and treatment of diseases or conditions involving inflammation. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of inflammation and other maladies, such as pain and diabetes, using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
    Type: Grant
    Filed: June 8, 1999
    Date of Patent: January 30, 2001
    Assignee: Amgen Inc.
    Inventors: Jeffery A. Zablocki, Eugene Tarlton, Jr., James P. Rizzi, Nathan B. Mantlo
  • Patent number: 6140347
    Abstract: A class of compounds of formula (I) wherein Z, E, Q, T, U, V, W, M, R.sup.1, R.sup.7 and R.sup.8 are as defined herein; are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.alpha. receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT.sub.1D.alpha. receptor subtype relative to the 5-HT.sub.1D.beta. subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT.sub.1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists.
    Type: Grant
    Filed: October 14, 1998
    Date of Patent: October 31, 2000
    Assignee: Merck Sharp & Dohme Ltd.
    Inventors: Jose Luis Castro Pineiro, Andrew Madin, Joseph George Neduvelil, Graham Andrew Showell, Leslie Joseph Street, Monique Bodil Van Niel
  • Patent number: 6133452
    Abstract: The present invention provides for the reaction of optionally substituted indole-3-acetamides with optionally substituted methyl indole-3-glyoxyl reagent to prepare potent PKC inhibitors. The reaction is very efficient and robust macrocyclization methodology.
    Type: Grant
    Filed: January 21, 1999
    Date of Patent: October 17, 2000
    Assignee: Eli Lilly and Company
    Inventors: Margaret Mary Faul, Leonard Larry Winneroski, Jr.
  • Patent number: 6130239
    Abstract: Disclosed are novel 4-alkenyl- and 4-alkynyl oxindoles having the formula ##STR1## and the pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2, R.sup.3, a, b, and X are as defined herein. These compounds inhibit cyclin-dependent kinases (CDKs), in particular CDK2. These compounds and their pharmaceutically acceptable salts, and prodrugs of said compounds, are anti-proliferative agents useful in the treatment or control of cell proliferative disorders, in particular cancer, more particularly, the treatment or control of breast and colon tumors. Also disclosed are pharmaceutical compositions containing the compounds of formula I and II as well as intermediates useful in the preparation of the compounds of formula I and II.
    Type: Grant
    Filed: December 15, 1999
    Date of Patent: October 10, 2000
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Yi Chen, Wendy Lea Corbett, Apostolos Dermatakis, Jin-Jun Liu, Kin-Chun Luk, Paige E. Mahaney, Steven Gregory Mischke
  • 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: 6063804
    Abstract: Compounds of formula (I): ##STR1## wherein: R represents hydrogen, alkyl, optionally-substituted amino, or linear or branched (C.sub.1 -C.sub.6)-acyl,R.sub.1 and R.sub.2, which may be identical or different, each represents independently of the other aryl, heteroaryl, or (C.sub.5 -C.sub.7)-cycloalkyl, or one of those groups optionally substituted,A, together with the atoms in common with the pyrrole, represents saturated or unsaturated, monocyclic or bicyclic (C.sub.3 -C.sub.12)-cycloalkyl, or a saturated heterocycle having 5 to 7 ring members and containing one or two nitrogen, or 7-oxabicyclo[2.2.1]heptane, or one of those groups optionally substituted,their isomers, and also addition salts thereof with a pharmaceutically-acceptable acid or base, pharmaceutical compositions thereof, and use thereof as medicaments.
    Type: Grant
    Filed: November 25, 1998
    Date of Patent: May 16, 2000
    Assignee: Adir et Compagnie
    Inventors: Guillaume De Nanteuil, Bernard Portevin, Jacqueline Bonnet, Charles Tordjman
  • Patent number: 6060473
    Abstract: 7-Azabicyclo[2.2.1]-heptane and -heptene derivatives are disclosed that can be administered to a mammal, including a human, to treat disorders associated with a decrease or increase in cholinergic activity.
    Type: Grant
    Filed: August 20, 1996
    Date of Patent: May 9, 2000
    Assignee: UCB S.A. - DTB
    Inventors: T. Y. Shen, W. Dean Harman, Dao Fei Huang, Javier Gonzalez
  • Patent number: 6046138
    Abstract: An indole derivative having the formula (I) or (II) and root formation inducing agents wherein these indole derivatives are an effective ingredient: ##STR1## wherein, R does not exist or represents a C.sub.1 to C.sub.4 alkylene group.
    Type: Grant
    Filed: March 10, 1998
    Date of Patent: April 4, 2000
    Assignee: Shiseido Company, Ltd.
    Inventors: Mineyuki Yokoyama, Shoko Yamaguchi, Seiichi Yoshida, Okihiko Sakamoto, Kiyotaka Kojima
  • Patent number: 6037475
    Abstract: The present invention provides a method for synthesizing indolylmaleimides by reacting an activated maleimide preferably with an optionally substituted organometalic-3-indole in the presence of a transition metal catalyst.
    Type: Grant
    Filed: February 11, 1999
    Date of Patent: March 14, 2000
    Assignee: Eli Lilly & Company
    Inventors: Margaret M. Faul, Michael R. Jirousek, John H. McDonald, III, David Andrew Neel
  • Patent number: 5998438
    Abstract: Described herein are compounds selective for a 5-HT.sub.1D -like receptor, which have the general formula: ##STR1## wherein A is selected from a six-membered, non-aromatic, optionally substituted carbocycle and a six-membered, non-aromatic, optionally substituted heterocycle having one or two heteroatoms selected from O, S, SO, SO.sub.2 and N.sup.4 ;R.sup.1 is selected from H and OH;n is 0 or 1 as permited by chemical structure;R.sup.2 is selected from CR.sup.5 CR.sup.6 CH.sub.2 NR.sup.7 R.sup.8 or a group of formula II, III or IV: ##STR2## R.sup.3 is selected from H and benzoyl; R.sup.4 is selected from H, loweralkyl, benzyl, loweralkylcarbonyl, loweralkylaminocarbonyl, loweralkylaminothiocarbonyl, loweralkanoyl, loweralkylaminoimide and loweralkoxy-substituted loweralkylene;R.sup.5 and R.sup.6 are independently selected from H, loweralkoxy and hydroxy;R.sup.7 and R.sup.8 are independently selected from H and loweralkyl or R.sup.7 and R.sup.
    Type: Grant
    Filed: November 21, 1997
    Date of Patent: December 7, 1999
    Assignee: Allelix Biopharmaceuticals, Inc.
    Inventors: Abdelmalik Slassi, Louise Edwards, Qingchang Meng, Sumanas Rakhit
  • Patent number: 5968923
    Abstract: The present invention provides compounds of formula (I) and the pharmaceutically acceptable salts thereof, wherein R is C.sub.3 -C.sub.7 cycloalkyl, aryl or C.sub.1 -C.sub.6 alkyl, said C.sub.1 -C.sub.6 alkyl, said C.sub.1 -C.sub.6 alkyl being optionally substituted by fluoro, COOH, --COO(C.sub.1 -C.sub.4 alkyl), C.sub.3 -C.sub.7 cycloalkyl, adamantyl, aryl or het.sup.1, and said C.sub.3 -C.sub.7 cycloalkyl being optionally substituted by 1 or 2 substituents each independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.4 alkoxy, hydroxy, fluoro, fluoro (C.sub.1 -C.sub.4) alkyl and fluoro (C.sub.1 -C.sub.4) Alkoxy; R.sub.1 is phenyl, naphthyl, thienyl, benzothienyl or indolyl, each optionally substituted by 1 or 2 substituents each independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo and trifluormethyl; R.sup.2 is --CO.sub.2 H, --CONR.sup.3 R.sup.4, --CONR.sup.5 (C.sub.3 -C.sub.7 cycloalkyl), --NR.sup.5 (C.sub.2 -C.sub.5 alkanoyl), --NR.sup.
    Type: Grant
    Filed: February 10, 1997
    Date of Patent: October 19, 1999
    Assignee: Pfizer Inc.
    Inventors: Alexander Roderick MacKenzie, Allan Patrick Marchington, Sandra Dora Meadows, Donald Stuart Middleton
  • Patent number: 5958943
    Abstract: The present invention relates to heterocyclic compounds of the formula ##STR1## in which R.sup.1 -R.sup.7, B, a and X have the meanings recited in the specification. These compounds are usable in the treatment of diseases of the rheumatoid variety and for the prevention of allergically induced diseases.
    Type: Grant
    Filed: March 28, 1996
    Date of Patent: September 28, 1999
    Assignee: Merckle GmbH
    Inventors: Stefan Laufer, Hans Gunther Striegel, Gerd Dannhardt
  • Patent number: 5929094
    Abstract: The present invention is directed to certain novel compounds represented by structural formula I: ##STR1## or a pharmaceutically acceptable salt thereof, wherein R.sup.3, R.sup.6, R.sup.7, R.sup.8, R.sup.11, R.sup.12, R.sup.13, A, m, n and the dashed lines are defined herein. The invention is also concerned with pharmaceutical formulations comprising these novel compounds as active ingredients and the use of the novel compounds and their formulations in the treatment of certain disorders. The compounds of this invention are tachykinin receptor antagonists and are useful in the treatment of inflammatory diseases, pain or migraine, asthma and emesis.
    Type: Grant
    Filed: October 22, 1997
    Date of Patent: July 27, 1999
    Assignee: Merck & Co., Inc.
    Inventors: Philippe Durette, Ihor Kopka, Malcolm MacCoss, Sander Mills
  • Patent number: 5919946
    Abstract: The present invention provides a method for synthesizing indolylmaleimides by reacting an activated maleimide preferably with an optionally substituted organometallic-3-indole in the presence of a transition metal catalyst.
    Type: Grant
    Filed: March 20, 1997
    Date of Patent: July 6, 1999
    Assignee: Eli Lilly and Company
    Inventors: Margaret M. Faul, Michael R. Jirousek, John H. McDonald, III, David Neel
  • Patent number: 5891901
    Abstract: Compounds of the formula ##STR1## wherein R is alkyl, alkylthio or hydroxy, as well as, pharmaceutically acceptable salts of compounds of formula I are antiproliferative agents useful in the treatment of cancer.
    Type: Grant
    Filed: July 24, 1997
    Date of Patent: April 6, 1999
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Urvashi Hooda Dhingra, Donna Mary Huryn, Dennis Dalton Keith, Giuseppe Federico Weber
  • Patent number: 5865857
    Abstract: A dye of Formula (1): ##STR1## wherein: D is a group of Formula (2): ##STR2## or a group of Formula (3): ##STR3## or a group of Formula (4): ##STR4## The variables are defined in the disclosures. The dyes and dye mixtures produce blue to green shades on synthetic textile materials such as polyester which have good build up and good light- and wet-fastness.
    Type: Grant
    Filed: June 19, 1997
    Date of Patent: February 2, 1999
    Assignee: Zeneca Limited
    Inventors: Denise Cavanagh, Mark Robert James, Barry Huston Meyrick, Paul Wight
  • Patent number: 5859261
    Abstract: The present invention provides a method for synthesizing indolylmaleimides by reacting an activated maleimide preferably with an optionally substituted organometallic-3-indole in the presence of a transition metal catalyst.
    Type: Grant
    Filed: December 19, 1997
    Date of Patent: January 12, 1999
    Assignee: Eli Lilly and Company
    Inventors: Margaret M. Faul, Michael R. Jirousek, John H. McDonald, III, David Andrew Neel
  • Patent number: 5856517
    Abstract: Compounds of the formula ##STR1## wherein R.sup.1 and R.sup.1' are independently alkyl, aryl, alkenyl or alkynyl;R.sup.2 and R.sup.2' are independently hydrogen or alkyl;R.sup.4, R.sup.5, R.sup.6 and R.sup.7 each independently are ##STR2## CH.sub.2 OR.sup.10, CHO, CH.sub.2 NR.sup.11 R.sup.12, hydrogen, halogen, cyano, alkyl, hydroxy, alkoxy, aryloxy, haloalkyl, nitro, amino, acylamino, aralkyloxy, monoalkylamino, dialkylamino, alkylthio, alkylsulphinyl or alkylsulphonyl, provided that at least one of R.sup.4, R.sup.5, R.sup.6 or R.sup.7 is cyano, ##STR3## CH.sub.2 OR.sup.10, CH.sub.2 NR.sup.11 R.sup.12, or CHO ; R.sup.8 is alkyl, aralkyl or aryl;R.sup.10 is hydrogen, alkyl, aralkyl or aryl;R.sup.11 and R.sup.
    Type: Grant
    Filed: July 24, 1997
    Date of Patent: January 5, 1999
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Donna Mary Huryn, Dennis Dalton Keith
  • Patent number: 5808094
    Abstract: A process for the preparation of mixed crystals of 1,4-diketopyrrolo?3,4-c!pyrroles, consisting of 1 mol each of two different compounds of formula ##STR1## by heating a corresponding mixture in solid form to the temperature range from 220.degree. to 380.degree. C.A and B are, for example, each a group of formula ##STR2## wherein R.sub.1 and R.sub.2 are each independently hydrogen, chloro, bromo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylamino, phenyl or --CN,G is --O--, --NR.sub.7 --, --N.dbd.N-- or --SO.sub.2 --,R.sub.3 and R.sub.4 are hydrogen, and R.sub.7 is hydrogen, methyl or ethyl.The mixed crystals and solid solutions obtained are excellently suited for pigmenting high molecular weight material.
    Type: Grant
    Filed: July 22, 1997
    Date of Patent: September 15, 1998
    Assignee: Ciba Specialty Chemicals Corporation
    Inventors: Jin Mizuguchi, Zhimin Hao, Olof Wallquist, Abul Iqbal
  • Patent number: 5808064
    Abstract: We have found that 2-unsubstituted indoles of structural formula (IV) can be cost-effectively synthesized in high yield by the palladium-catalyzed coupling/ring closure of a 2-halo or 2-trifluoromethylsulfonyloxy aniline (I) and an acyl silane derivative (II), followed by deprotection of the silyl protecting groups. ##STR1## The process of the present invention is particularly useful to form indoles containing acid-labile substituents such as triazole, acetyl, ketal, cyano, and carbamate, or indoles having a good leaving group in the benzyl position. The advantages of the present process are that it does not require the use of triphenyl phosphine or tetrabutyl ammonium chloride or lithium chloride. When applied to 5-triazolyl substituted indoles, the present process also eliminates the tendency of triazolyl polymerization in the Fischer indole synthesis.
    Type: Grant
    Filed: August 7, 1997
    Date of Patent: September 15, 1998
    Assignee: Merck & Co., Inc.
    Inventors: Cheng-Yi Chen, Robert D. Larsen
  • Patent number: 5773612
    Abstract: A compound of formula II' ##STR1## in whichR.sub.I is an ethoxy group or a chlorine atom;R.sub.II is hydrogen, a chlorine atom or a methyl group;R.sub.III is a chlorophenyl group or a methoxyphenyl group;R.sub.IV is an amino group, a group NR.sub.9 R.sub.10 or NR.sub.9 R.sub.XI, or a piperazin-1-yl radical substituted in the 4-position by a (C.sub.2 -C.sub.10)alkylene group substituted by an amino group which is free or carries a protective group;R.sub.10 is (CH.sub.2).sub.p R.sub.35 or a (C.sub.2 -C.sub.10)alkylene group substituted by R.sub.21 ;R.sub.XI is a (C.sub.1 -C.sub.12)alkyl group or a group .omega.-R.sub.32 R.sub.33 N(C.sub.1 -C.sub.4)-alkylcarbonyl; andR.sub.21 is R.sub.36 ; a group OR.sub.37 ; a group NR.sub.32 R.sub.33 ; a cyano group; a group S(C.sub.1 -C.sub.7)alkyl; a group SO(C.sub.1 -C.sub.7)alkyl; or a group SO.sub.2 (C.sub.1 -C.sub.7)alkyl;R.sub.35 is a piperid-4-yl group which is unsubstituted or substituted in the 1-position by a (C.sub.1 -C.sub.7)alkoxycarbonyl group or by a (C.sub.
    Type: Grant
    Filed: April 30, 1996
    Date of Patent: June 30, 1998
    Assignee: Sanofi
    Inventors: Jean Wagnon, Bernard Tonnerre, Alain Di Malta, Richard Roux, Marie-Sophie Amiel, Claudine Serradeil-Legal
  • Patent number: 5770742
    Abstract: 5-Thiophene-substituted tryptamine analogs are provided, which exhibit selectivity towards 5-HT.sub.D1 receptors and consequently show potential in alleviation of the symptoms of migraine. The analogs are represented by the following general chemical formula: ##STR1## in which X represents H, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 hydroxyalkyl or halogen, at the 4- or 5-position of the thiophene nucleus; Y represents a direct bond or a C.sub.1 -C.sub.3 alkylene group optionally substituted with hydroxyl: and Z represents amino, mono- or di-N-lower alkyl-substituted amino, or optionally N-lower alkyl-substituted pyrrolidine.
    Type: Grant
    Filed: May 16, 1996
    Date of Patent: June 23, 1998
    Assignee: Allelix Biopharmaceuticals Inc.
    Inventors: Qingchang Meng, Abdelmalik Slassi, Sumanas Rakhit
  • Patent number: 5750702
    Abstract: The present invention encompasses structures of the formula: ##STR1## or the pharmaceutically acceptable non-toxic salts thereof wherein: ##STR2## wherein: W represents substituted or unsubstituted phenyl;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; andn 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: July 16, 1996
    Date of Patent: May 12, 1998
    Assignee: Neurogen Corporation
    Inventors: Pamela Albaugh, Alan Hutchison
  • Patent number: 5736564
    Abstract: The present invention relates to dihydroisoindole compounds, pharmaceutical compositions containing these compounds, and their use as endothelin receptor antagonists.
    Type: Grant
    Filed: December 12, 1996
    Date of Patent: April 7, 1998
    Assignee: SmithKline Beecham Corporation
    Inventors: John Duncan Elliott, Robert Gene Franz, M. Amparo Lago, Aiming Gao
  • Patent number: 5726063
    Abstract: A colorimetric assay of enaldehydes or of malonic dialdehyde as lipid peroxidation indices in an aqueous medium includinga) addition to the medium of a reagent of a compound of general formula I and their optional addition salts with organic or inorganic bases or with organic or inorganic acids. ##STR1## in which formula: A and C, which may be identical or different, each represent H, ##STR2## wherein A and C cannot simultaneously represent H, with:R.sup.1 =H; alkyl; aralkyl; aryl substituted on the aryl ring; alkyl sulfonate Y.sup.+ ; alkyl phosphonate, Y.sup.+ ; or alkyl carboxylate, Y.sup.+ ;R.sup.2 =H; --OR.sup.4 ; F; Cl; Br; I; --NO.sub.2 ; SO.sub.3.sup.31 Y.sup.+ ; --CN; --COOR.sup.4 ; or --CONR.sup.5 R.sup.6 ;R.sup.3 =H; --OR.sup.4 ; --NR.sup.5 R.sup.6 ; --SR.sup.4 ; F; Cl; Br; I; --NO.sub.2 ; --SO.sub.3 --Y.sup.+ ; --CN; --COR.sup.5 ; --COOR.sup.4 ; or --CONR.sup.5 R.sup.6 ;R.sup.4 =H; alkyl; aralkyl; or aryl substituted on the aryl ring;R.sup.
    Type: Grant
    Filed: August 23, 1996
    Date of Patent: March 10, 1998
    Assignee: Oxis Isle of Man, Limited
    Inventors: Dominique Gerard-Monnier, Irene Erdelmeier, Jean Chaudiere, Jean-Claude Yadan
  • Patent number: 5708169
    Abstract: The present invention provides for new 5-amidomethyl, .alpha.,.beta.-saturated and--unsaturated butyrolactone antibacterial agents of formula I ##STR1## characterized by 3-aryl substituents that include, for example, indolinyl and phenyl substituted with zero (0) to two(2) halogen atoms and substituted in the para position with, e.g., piperazinyl, thiomorpholinyl (and corresponding sulfoxide and sulfone), thiazolidinyl (and sulfoxide and sulfone), morpholinyl, azetidinyl, pyrrolidinyl, piperidinyl, pyrrolyl, azepinyl, troponyl, 3,7-diazabicyclo?3.3.0!octan-3-yl, bridged thiazinyl or bridged oxazinyl moieties. In those cases where a ring nitrogen is present, then this is substituted to form an amide, formamide, sulfonamide, urethane, or alkylated with a wide variety of moieties.
    Type: Grant
    Filed: September 5, 1996
    Date of Patent: January 13, 1998
    Assignee: Pharmacia & Upjohn Company
    Inventors: Jackson B. Hester, Jr., Steven Joseph Brickner, Michael Robert Barbachyn, Douglas K. Hutchinson, Dana Scott Toops
  • Patent number: 5693824
    Abstract: A process for the preparation of mixed crystals of 1,4-diketopyrrolo?3,4-c!pyrroles, consisting of 1 mol each of two different compounds of formula ##STR1## by heating a corresponding mixture in solid form to the temperature range from 220.degree. to 380.degree. C.A and B are, for example, each a group of formula ##STR2## wherein R.sub.1 and R.sub.2 are each independently hydrogen, chloro, bromo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylamino, phenyl or --CN, G is --O--, --NR.sub.7 --, --N.dbd.N-- or --SO.sub.2 --, R.sub.3 and R.sub.4 are hydrogen, and R.sub.7 is hydrogen, methyl or ethyl.The mixed crystals and solid solutions obtained are excellently suited for pigmenting high molecular weight material.
    Type: Grant
    Filed: September 12, 1996
    Date of Patent: December 2, 1997
    Assignee: Ciba Specialty Chemicals Corporation
    Inventors: Jin Mizuguchi, Zhimin Hao, Olof Wallquist, Abul Iqbal
  • Patent number: 5691373
    Abstract: Novel nonpeptide antagonists of endothelin I are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin, acute and chronic renal failure, hypertension, myocardial infarction, myocardial ischemia, cerebral vasospasm, cerebral ischemia, cerebral infarction, cirrhosis, septic shock, congestive heart failure, endotoxic shock, subarachnoid hemorrhage, arrhythmias, asthma, preeclampsia, atherosclerotic disorders including Raynaud's disease and restenosis, angina, cancer, pulmonary hypertension, ischemic disease, gastric mucosal damage, hemorrhagic shock, ischemic bowel disease, stroke, benign prosthatic hyperplasia (BPH), and diabetes.
    Type: Grant
    Filed: February 6, 1995
    Date of Patent: November 25, 1997
    Assignee: Warner-Lambert Company
    Inventors: Kent Alan Berryman, Annette Marian Doherty, Jeremy John Edmunds, William Chester Patt, Mark Stephen Plummer, Joseph Thomas Repine
  • Patent number: 5672618
    Abstract: The present invention discloses compounds that are highly isozyme selective protein kinase C beta-1 and beta-2 isozyme inhibitors. Accordingly, the present invention provides a method of selectively inhibiting protein kinase C isozymes beta-1, and beta-2. As isozyme selective inhibitors of beta-1 and beta-2, the compounds are therapeutically useful in treating conditions associated with diabetes mellitus and its complications, as well as other disease states associated with an elevation of the beta-1 and beta-2 isozyme.
    Type: Grant
    Filed: May 25, 1995
    Date of Patent: September 30, 1997
    Assignee: Eli Lilly and Company
    Inventors: William F. Heath, Jr., John H. McDonald, III, Michael Paal, Theo Schotten, Wolfgang Stenzel
  • Patent number: 5668152
    Abstract: The present invention discloses compounds that are highly isozyme selective protein kinase C beta-1 and beta-2 isozyme inhibitors. Accordingly, the present invention provides a method of selectively inhibiting protein kinase C isozymes beta-1, and beta-2. As isozyme selective inhibitors of beta-1 and beta-2, the compounds are therapeutically useful in treating conditions associated with diabetes mellitus and its complications, as well as other disease states associated with an elevation of the beta-1 and beta-2 isozyme.
    Type: Grant
    Filed: May 25, 1995
    Date of Patent: September 16, 1997
    Assignee: Eli Lilly and Company
    Inventors: William F. Heath, Jr., John H. McDonald, III, Gerd Ruhter, Theo Schotten
  • Patent number: 5665723
    Abstract: Fibrinogen receptor antagonists having the formula ##STR1## for example ##STR2##
    Type: Grant
    Filed: June 2, 1995
    Date of Patent: September 9, 1997
    Assignee: Merck & Co., Inc.
    Inventors: George D. Hartman, John H. Hutchinson, Wasyl Halczenko
  • Patent number: 5660598
    Abstract: A dye of Formula (1): ##STR1## wherein: D is a group of Formula (2): ##STR2## or a group of Formula (3): ##STR3## or a group of Formula (4): ##STR4## The variables are defined in the specification. The dyes and dye mixtures produce blue to green shades on synthetic textile materials such as polyester which have good build up and good light- and wet-fastness.
    Type: Grant
    Filed: May 3, 1995
    Date of Patent: August 26, 1997
    Assignee: Zeneca Limited
    Inventors: Denise Cavanagh, Mark Robert James, Barry Huston Meyrick, Paul Wight
  • Patent number: RE36736
    Abstract: Compounds of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, X and Y have the signficance given in the description, are useful in the control or prevention of inflammatory, immunological, bronchopulmonary or cardiovascular disorders.
    Type: Grant
    Filed: January 27, 1998
    Date of Patent: June 13, 2000
    Assignee: Hoffman-La Roche Inc.
    Inventors: Peter D. Davis, Christopher H. Hill, Geoffrey Lawton