Abstract: This invention relates to compounds which are generally muscarinic M2/M3 receptor antagonists and which are represented by Formula I:
wherein R1, R2, R3 and R4 are as defined in the specification, or individual isomers, racemic or non-racemic mixtures of isomers, or acceptable salts or solvates thereof. The invention further relates to pharmaceutical compositions containing such compounds and methods for their use and preparation as therapeutic drugs.
Abstract: A series of activated iodo-benzamide derivatives are described as antineoplastic and antiviral drug compounds. The compounds generally possess a chelating group, a thiol trapping group and an activating group. The presumptive mechanism of action in preventing cancer cell and virus replication is through inhibition of the binding of transcription factors to zinc finger binding domains. The compounds are effective in inhibiting growth of a variety of human and animal tumor and leukemia cell lines at low concentrations.
Type:
Application
Filed:
November 25, 2002
Publication date:
October 2, 2003
Inventors:
Randall W. Yatscoff, Robert T. Foster, Selvaraj Naicker
Abstract: A novel class of substituted piperidines, pharmaceutical compositions comprising them and use thereof in the treatment and/or prevention of diseases and disorders related to the histamine H3 receptor. More particularly, the compounds are useful for the treatment and/or prevention of diseases and disorders in which an interaction with the histamine H3 receptor is beneficial.
Abstract: The invention provides an immunogen comprising a hapten coupled to an antigenicity-conferring carrier material, a conjugate comprising the aforementioned hapten coupled to a labelling agent, as well as, antibodies raised against the aforementioned immunogen and capable of binding with at least one structural epitope of metabolites of fentanyl and of metabolites of fentanyl analogs.
Type:
Application
Filed:
November 15, 2002
Publication date:
September 11, 2003
Applicant:
Randox Laboratories Limited
Inventors:
Robert Ivan McConnell, Elouard Benchikh, Stephen Peter Fitzgerald, John Victor Lamont
Abstract: The present invention is directed to compounds useful as selective serine protease or dual-serine protease inhibitors, compositions thereof and methods for treating serine protease or dual-serine protease mediated disorders.
Type:
Application
Filed:
November 25, 2002
Publication date:
September 4, 2003
Inventors:
Michael N. Greco, Bruce E. Maryanoff, Michael J. Hawkins, Robert E. Boyd
Abstract: The present invention is directed to compounds useful as selective serine protease or dual-serine protease inhibitors, compositions thereof and methods for treating serine protease or dual-serine protease mediated disorders.
Type:
Application
Filed:
November 25, 2002
Publication date:
September 4, 2003
Inventors:
Michael N. Greco, Bruce E. Maryanoff, Michael J. Hawkins, Robert E. Boyd
Abstract: Certain substituted benzamide derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.
Type:
Application
Filed:
December 20, 2002
Publication date:
August 21, 2003
Inventors:
Fady Malik, Adam Lewis Tomasi, Bainian Feng, Bradley Paul Morgan, Han-Jie Zhou, Kathleen A. Elias, Pu-Ping Lu, Whitney Walter Smith, Xiangping Qian, David J. Morgans,
Abstract: The present application describes modulators of CCR3 of formula (I):
or pharmaceutically acceptable salt forms thereof, useful for the prevention of inflammatory diseases such as asthma and other allergic diseases.
Type:
Grant
Filed:
October 13, 2000
Date of Patent:
August 19, 2003
Assignee:
Bristol-Myers Squibb Pharma
Inventors:
Dean A Wacker, John V Duncia, Joseph B Santella, III, Daniel S Gardner
Abstract: A cyclic amine compound by the following general formula (1):
wherein,
R1, R2 and R3 each independently represent a hydrogen atom or an alkoxy group
W1 and W2 each independently represent N or CH;
X represents O, NR4, CONR4 or NR4CO;
R4 represents a hydrogen atom, or an alkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl group; and
l, m and n each represents a number of 0 or 1, a salt thereof and a hydrate thereof are provided. These compounds have inhibitory effects on both cell adhesion and cell infiltration and are useful as anti-asthmatic agents, anti-allergic agents, anti-rheumatic agents, anti-arteriosclerotic agents, anti-inflammatory agents, anti-Sjogren's syndrome agents or the like.
Abstract: The present invention relates to substituted bis-arylsulfonamide and arylsulfonamide compounds of the general formula (I) or the formula (II), which compounds are potentially useful for the prophylaxis and treatment of medical conditions relating to obesity, type II diabetes and/or disorders of the central nervous system.
Type:
Application
Filed:
May 13, 2002
Publication date:
August 7, 2003
Inventors:
Ulf Bremberg, Patrizia Caldirola, Annika J. Jensen, Gary Johansson, Andrew Mott, Lori Sutin, Jan Tejbrant
Abstract: This invention relates generally to heteroaryl-phenyl substituted compounds that are inhibitors of trypsin-like serine protease enzymes, especially factor Xa or thrombin, pharmaceutical compositions containing the same, and methods of using the same as anticoagulant agents for treatment and prevention of thromboembolic disorders.
Abstract: The invention relates to cyclic heteroaromatic compounds, containing at least one nitrogen atom, and to their use in the manufacture of medicaments for the treatment of diseases, related to adenosine receptor modulators, such as Alzheimer's disease, Parkinson's disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, asthma, allergic responses, hypoxia, ischaemia, seizure, substance abuse, sedation and they may be active as muscle relaxants, antipsychotics, anti epileptics, anticonvulsants and cardiaprotective agents.
Type:
Grant
Filed:
February 20, 2001
Date of Patent:
July 1, 2003
Assignee:
Hoffman-La Roche Inc.
Inventors:
Edilio Maurizio Borroni, Gerda Huber-Trottmann, Gavin John Kilpatrick, Roger David Norcross
Abstract: Novel 4-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using 4-substituted piperidine analogs as selectively active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headaches, glaucoma, CMV retinitis, chronic pain, opioid tolerance or withdrawals, or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease are described. Also described are novel methods for preparing 4-substituted piperidine analogs and novel intermediates of the 4-substituted piperidine analogs.
Type:
Application
Filed:
July 29, 2002
Publication date:
June 5, 2003
Inventors:
Christopher F. Bigge, Jonathan Wright, Sui Xiong Cai, Eckard Weber, Richard Woodward, Nancy F. Lan, Zhang-Lin Zhou, John F.W. Keana
Abstract: To provide a novel, industrially superior process for producing a 1,4-substituted cyclic amine compound which is useful as a pharmaceutical, and an intermediate for the process. That is, a process for producing an indole compound (I), which comprises reducing a 1,4-subsutituted 2-nitrophenyl compound (VII) to give a 1,4-substituted 2-aminophenyl compound (V); reacting the compound (V) with an N-substituted 4-piperidone compound (VI) to give a 1,4-substituted 2-piperidylaminophenyl compound (IV); cyclizing the compound (IV) to give a 2-oxoindoline compound (III); halogenating the compound (III) to give a 2-halogenated indole compound (II); reducing the compound (II); and if necessary subjecting the resulting compound to alcoholysis or aminolysis.
wherein each of R1 and R2 represents a substituent; X represents a halogen atom; and n is a numerical subscript.
Abstract: Sulfonamide lactams of the following formula
wherein X, R1, R2, R3, R4, R4a, R5, R5a, R6, R6a, R7 and R8 are as described herein, are provided which inhibitors of Factor Xa and are useful as anticoagulants in the treatment of cardiovascular diseases associated with thromboses.
Type:
Grant
Filed:
January 29, 2002
Date of Patent:
April 29, 2003
Assignee:
Bristol-Myers Squibb Company
Inventors:
Stephen P. O'Connor, Michael Lawrence, Yan Shi, Philip D. Stein
Abstract: The present invention relates compounds of the formula (I):
wherein
X represents hydrogen or a C1-4alkyl group optionally substituted by a hydroxy group;
Y represents hydrogen, C1-6alkyl or C3-7cycloalkyl;
Z is —CR9R10CH2— or —CH2CR9R10—;
R represents hydrogen, fluorine, hydroxy, C1-6alkyl or C1-6alkoxy;
and R1, R2, R3, R4, R5 and R6 are as defined herein.
The compounds are of particular use in the treatment of depression, anxiety, pain, inflammation, migraine, emesis or postherpetic neuralgia.
Type:
Grant
Filed:
April 1, 2002
Date of Patent:
April 29, 2003
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Janusz Jozef Kulagowski, Piotr Antoni Raubo, Christopher George Thomson
Abstract: This invention is directed to sulfonyl aromatic hydroxamic acid compounds and salts thereof that, inter alia, inhibit matrix metalloprotease (MMP) activity and/or aggrecanase activity.
Type:
Application
Filed:
July 19, 2001
Publication date:
April 17, 2003
Inventors:
Thomas E. Barta, Daniel P. Becker, Louis J. Bedell, Gary A. DeCrescenzo, John N. Freskos, Daniel P. Getman, Joseph J. McDonald, Brent V. Mischke, Shashidhar N. Rao, Clara I. Villamil
Abstract: The present invention relates to selected 1-alkoxy-2,2 diethyl-6,6 dimethyl piperidine and 1-alkoxy-2,6 diethyl-2,3,6 trimethyl piperidine derivatives which are substituted in the 4 position by an oxygen or nitrogen atom; a polymerizable composition comprising a) at least one ethylenically unsaturated monomer and b) said piperidine derivatives. Further aspects of the present invention are a process for polymerizing ethylenically unsaturated monomers, and the use of 1-alkoxy-2,2 diethyl-6,6 dimethyl piperidine and 1-alkoxy-2,6 diethyl-2,6 dimethyl piperidine derivatives which are substituted in the 4 position by an oxygen or nitrogen atom for controlled polymerization. The intermediate N-oxyl derivatives, a composition of the N-oxyl derivatives with ethylenically unsaturated monomers and a free radical initiator, as well as a process for polymerization are also subjects of the present invention.
Type:
Application
Filed:
March 19, 2001
Publication date:
April 3, 2003
Inventors:
Peter Nesvadba, Marie-Odile Zink, Andreas Kramer
Abstract: Alkylsulfonamido heterocyclic thrombin inhibitors are provided which have the structure
wherein G is
wherein
n is 0, 1 or 2 or 3; m is 0, 1, 2 or 3; Y is NH or S;
R is hydrogen, hydroxyalkyl, aminoalkyl, alkyl, cycloalkyl, amidoalkyl, arylalkyl, alkenyl, aryl, alkynyl, arylalkoxyalkyl, or an amino acid side chain;
R1 and R2 are independently hydrogen, lower alkyl, cycloalkyl, aryl, hydroxy, alkoxy, oxo, thioketal, thioalkyl, thioaryl, amino or alkylamino; or R1 and R2 can be taken together with the carbons to which they are attached to form a cycloalkyl, aryl or heteroaryl ring.
Type:
Grant
Filed:
March 16, 1994
Date of Patent:
March 18, 2003
Assignee:
Bristol-Myers Squibb Company
Inventors:
Spencer D. Kimball, Jagabandhu Das, Wan Fang Lau
Abstract: Trisubstituted pyrroles are antiprotozoal agents useful in the treatment and prevention of protozoal diseases in human and animals, including the control of coccidiosis in poultry.
Type:
Grant
Filed:
November 10, 2000
Date of Patent:
March 4, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Tesfaye Bitfu, Danqing D. Feng, Gui-Bai Liang, Mitree M. Ponpipom, Xiaoxia Qian, Michael H. Fisher, Matthew J. Wyvratt, Robert L. Bugianesi
Abstract: This invention provides compounds of Formula I having the structure
wherein,
R1, R2, R3, R4, R5, T, T1, T2, and X are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.
Type:
Grant
Filed:
July 12, 2001
Date of Patent:
February 25, 2003
Assignee:
Wyeth
Inventors:
Baihua Hu, Fuk-Wah Sum, Michael S. Malamas
Abstract: Compounds of general formula (I), R1 is selected from any one of phenyl, pyridinyl, thiophenyl, furanyl, imidazolyl, and triazolyl; where each R1 phenyl ring and R1 heteroaromatic ring may optionally and independently be further substituted by 1, 2 or 3 substituents selected from straight and branched C1-C6 alkyl, NO2, CF3, C1-C6 alkoxy, chloro, fluoro, bromo, and iodo. The substitutions on the phenyl ring and on the heteroaromatic ring may take place in any position on said ring systems; Ra and Rb is each and individually selected from any one of hydrogen, a straight and branched C1-C6 alkyl, NO2, CF3, C1-C6 alkoxy, chloro, fluoro, bromo, and iodo; are disclosed and claimed in the present application, as well as their pharmaceutically acceptable salts and pharmaceutical compositions comprising the novel compounds and their use in therapy, in particular in the management of pain.
Abstract: The present invention relates to nitric oxide-releasing amidine- and enamine-derived diazeniumdiolates, compositions comprising such compounds, methods of using such compounds and compositions, and to a method for the preparation of nitric oxide-releasing amidine and enamine derived diazeniumdiolates via the direct reaction of nitric oxide with amidines and enamines, and to a method of converting amines into such compounds.
Type:
Grant
Filed:
April 3, 2001
Date of Patent:
January 28, 2003
Assignee:
The United States of America as represented by the Department
of Health and Human Services
Abstract: This invention provides compounds of Formula I having the structure
and X are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.
Abstract: The invention provides a compound of formula (I):
and its pharmaceutically acceptable salts, wherein
R is halo C2-C8 alkenyl or halo C2-C8 alkynyl;
R1 is hydrogen, halo or C1-C6 alkoxy;
or R and R1, together with the two carbon atoms to which they are attached, form a C4-C6 cycloalkyl or a C4-C6 oxacycloalkyl ring wherein said ring may be optionally substituted by one or more substituents selected from the group consisting of halo, C1-C6 alkyl and halo C1-C6 alkyl;
X is C1-C6 alkoxy, halo C1-C6 alkoxy, phenoxy or halo; and
Ar is phenyl optionally substituted by halo.
These compounds are useful in the treatment of a gastrointestinal disorder; a central nervous system (CNS) disorder; an inflammatory disease; emesis; urinary incontinence; pain; migraine; sunburn; diseases, disorders and adverse conditions caused by Heliobacter pylori; or angiogenesis especially CNS disorders in a mammalian subject, especially humans.
Abstract: The present invention is directed to compounds useful as selective serine protease or dual-serine protease inhibitors, compositions thereof and methods for treating serine protease or dual-serine protease mediated disorders.
Type:
Application
Filed:
March 5, 2002
Publication date:
January 2, 2003
Inventors:
Michael N. Greco, Bruce E. Maryanoff, Michael J. Hawkins, Robert E. Boyd
Abstract: This invention provides compounds of Formula I having the structure
wherein R1, R2, R3, W, X, and Z are as defined hereinbefore or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.
Abstract: A cyclic amine compound represented by the following general formula (1):
wherein,
R1, R2 and R3 each independently represent a hydrogen atom or an alkoxy group;
W1 an W2 each independently represent N or CH;
X represents O, NR4, CONR4 or NR4CO;
R4 each independently represents a hydrogen atom, or an alkyl, aryl, heteroaryl, aralkyl, or heteroalkyl group; and
l, m and n each represents a number of 0 to 1, a salt thereof and a hydrate thereof are provided.
These compounds have inhibitory effects on both cell adhesion and cell infiltration and are useful as anti-asthmatic agents, anti-allergic agents, anti-rheumatic agents, anti-arteriosclerotic agents, anti-inflammatory agents, anti-Sjogren's syndrome agents or the like.
Abstract: Novel disulfide derivatives useful for preventing or treating allergic diseases of the eye, nose, skin, ear, gastrointestinal tract, airways or lung and preventing or treating manifestations of systemic mastocytosis are disclosed. The disulfide derivatives act as mast cell stabilizers.
Type:
Application
Filed:
May 22, 2002
Publication date:
December 19, 2002
Inventors:
Zixia Feng, Mark R. Hellberg, Steven T. Miller
Abstract: The present invention provides 2-piperidone compounds or pharmaceutically acceptable salts thereof, which have a potent activity of inhibiting the proliferation of tumor cells and thus are useful as medicaments, as well as antitumor agents containing these compounds. The 2-piperidone compound is represented by the following formula (I):
wherein
R1 represents —(CH2)nR1a {wherein n is an integer of from 0 to 5, and R1a represents amino, lower alkylamino, di(lower alkyl)amino, substituted or unsubstituted aryl, or a substituted or unsubstituted heterocyclic group}, and
R2 and R3 independently represent lower alkyl which may be substituted by lower alkoxycarboyl; lower alkenyl, aralkyl or lower alkynyl which may be substituted by substituted or unsubstituted aryl or a substituted or unsubstituted heterocyclic group; substituted or unsubstituted aryl; or a substituted or unsubstituted heterocyclic group.
Type:
Grant
Filed:
January 12, 2000
Date of Patent:
December 10, 2002
Assignees:
Kyowa Hakko Kogyo Co., Ltd., Eli Lilly & Co.
Abstract: The subject invention concerns novel analogs of fentanyl opioids. The subject invention also concerns methods for synthesizing the compounds of the invention. The invention also concerns methods for treating pain in a patient by administering a compound of the invention to a person in need of such treatment.
Abstract: Compounds of formula (I) are matrix metalloprotemase inhibitors wherein X represents a carboxylic acid group —COOH, or a hydroxamic acid group —CONHOH;R2 represents a radical of formula (II): R3—(ALK)m—(Q)p—(ALK)n.
Abstract: The present invention is directed to cyclic amines of the formula I:
(wherein R1, R2, R3, m and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-1, CCR-2, CCR-2A, CCR-2B, CCR-3, CCR-4, CCR-5, CXCR-3, and/or CXCR-4.
Type:
Grant
Filed:
October 17, 2000
Date of Patent:
November 5, 2002
Assignee:
Merck & Co., Inc.
Inventors:
Charles G. Caldwell, Paul E. Finke, Malcolm Maccoss, Sander G. Mills, Bryan Oates, Dooseop Kim, Shankaran Kothandaraman, Liping Wang
Abstract: Selected compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
Type:
Application
Filed:
January 10, 2002
Publication date:
October 10, 2002
Inventors:
Guoqing Chen, Guolin Cai, Celia Dominguez, Julie Germain, Joseph L. Kim, Tae-Seong Kim, Leon M. Smith, Andrew Tasker, Chester Chenguang Yuan, Shon Booker, Michael Croghan, Lucian DiPietro, Daniel Elbaum, Qi Huang, Ning Xi, Shimin Xu, Vinod F. Patel
Abstract: The invention relates to new compounds of general formula I
or the pharmaceutically acceptable salts thereof, wherein
X=N—R3 or CH—R4,
Y=CH2 or (CH2)2,
Z=O or H2;
and R1, R2, R3, R4 and Ar have the meanings given in the specification, and the preparation and use thereof. The new compounds are valuable neurokinin (tachykinin) antagonists.
Abstract: Novel 4-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using the 4-substituted piperidine analogs as selectively active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as cerebral ischemia, central nervous system trauma, hypoglycemia, neurodegenerative disorders, anxiety, migraine headaches, convulsions, aminoglycoside antibiotics-induced hearing loss, chronic pain, psychosis, glaucoma, CMV retinitis, opioid tolerance or withdrawal, urinary incontinence and neurodegenerative disorders such as lathyrism, Alzheimers' Disease, Parkinsonism, and Huntington's Disease are described. Also described are novel methods for preparing 4-substituted piperidine analogs and novel intermediates of the 4-substituted piperidine analogs.
Abstract: The present invention relates beta-amino acid derivatives for treating or preventing neuronal damage associated with neurological diseases. The invention also provides compositions comprising the compounds of the present invention and methods of utilizing those compositions for treating or preventing neuronal damage.