Abstract: The present invention relates to a method for the preparation for camptothecin and camptothecin-like compounds and to novel intermediates used in this preparation. In particular, the invention provides a process for the preparation of the camptothecin derivative of formula (I′) known by the chemical name “7-(4-methylpiperazinomethylene)-10,11-ethylenedioxy-20(R,S)-camptothecin”, which comprises cyclising the compound of formula (II′), wherein X is halogen, particularly chloro, bromo, or iodo; and when the compound of formula (I′) is obtained as a mixture of enantiomers optionally resolving the mixture to obtain the desired enantiomer; and/or if desired, converting the resulting compound of formula (I′) or a salt thereof into a physiologically acceptable salt or solvate thereof.
Type:
Application
Filed:
September 13, 2002
Publication date:
March 6, 2003
Applicant:
OSI Pharmaceuticals, Inc.
Inventors:
Francis Gerard Fang, Edward McDonald Huie, Shiping Xie, Daniel L. Comins
Abstract: Disclosed are compounds of the formula: 1
Type:
Application
Filed:
December 20, 2001
Publication date:
February 27, 2003
Inventors:
Timothy Guzi, Dinanath F. Rane, Alan K. Mallams, Alan B. Cooper, Ronald J. Doll, Viyyoor M. Girijavallabhan, Arthur G. Taveras, Corey Strickland, Joseph M. Kelly, Jianping Chao
Abstract: The present invention relates to substituted benzothiazole derivitives and to their pharmaceutically acceptable salts useful for the treatment of diseases related to the adenosine receptor.
Type:
Grant
Filed:
June 14, 2001
Date of Patent:
February 18, 2003
Assignee:
Hoffman-La Roche Inc.
Inventors:
Alexander Alanine, Alexander Flohr, Aubry Kern Miller, Roger David Norcross, Claus Riemer
Abstract: 1H-Imidazopyridine derivatives represented by the following general formula or salts thereof:
wherein R1 represents hydrogen atom, hydroxyl group, an alkyl group, a cycloalkyl group, styryl group, or an aryl group; R2 represents hydrogen atom, an alkyl group, a halogen atom, hydroxyl group, amino group, a cyclic amino group, or phenoxy group; ring A represents a homocyclic or heterocyclic ring which may be substituted; R3 represents a saturated nitrogen-containing heterocyclic group; and m represents an integer of from 0 to 3. The derivatives have excellent inhibitory actions against production of TNF or IL-1 and are extremely useful as preventive or therapeutic agents for diseases in which a cytokine is mediated.
Abstract: Disclosed are novel compounds and a method of treating a disease associated with aberrant leukocyte recruitment and/or activation. The method comprises administering to a subject in need an effective amount of a compound represented by:
and physiologically acceptable salts thereof.
Abstract: This invention provides a serotonin 5-HT3 receptor partial activator which has a serotonin 5-HT3 receptor activating action, in addition to its serotonin 5-HT3 receptor antagonism, and does not cause constipation as a side effect.
Abstract: The present invention discloses novel substituted imidazole compounds which have dual histamine-H1 and H3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy, inflammatory and CNS-related diseases and others.
Type:
Grant
Filed:
September 18, 2001
Date of Patent:
January 14, 2003
Assignee:
Schering Corporation
Inventors:
Neng-Yang Shih, Daniel M. Solomon, John J. Piwinski, Andrew T. Lupo, Jr., Michael J. Green
Abstract: The present invention discloses novel tricyclic compounds represented by the formula (1.
Type:
Application
Filed:
August 28, 2001
Publication date:
December 26, 2002
Inventors:
F. George Njoroge, Bancha Vibulbhan, Alan B. Cooper, Timothy Guzi, Dinanath F. Rane, Keith P. Minor, Ronald J. Doll, Viyyoor M. Girijavallabhan, Bama Santhanam, Patrick A. Pinto, Hugh Y. Zhu, Kartik M. Keertikar, Carmen S. Alvarez, John J. Baldwin, Ge Li, Chia-Yu Huang, Ray A. James, W. Robert Bishop, James J-S Wang, Jagdish A. Desai
Abstract: Disclosed are 1-Azatricyclic-4-benzylpiperazine compounds which are useful for the treatment and/or prevention of neuropsychological disorders including, but not limited to, schizophrenia, mania, dementia, depression, anxiety, compulsive behavior, substance abuse, Parkinson-like motor disorders and motion disorders related to the use of neuroleptic agents. Pharmaceutical compositions, including packaged pharmaceutical compositions, are further provided. Compounds of the invention are also useful as probes for the localization of GABAA receptors in tissue samples.
Type:
Application
Filed:
May 7, 2002
Publication date:
December 19, 2002
Applicant:
Neurogen Corporation
Inventors:
Xiaoyan Zhang, Kevin Hodgetts, Stanislaw Rachwal, Daniel Rosewater, Andrew Thurkauf
Abstract: Novel triazolo derivatives represented by the following formula and pharmaceutically acceptable salts thereof, as well as chemokine inhibitors containing the same as an effective component. These are useful as therapeutic agents for allergic diseases such as bronchial asthma and atopic dermatitis; therapeutic agents for inflammatory diseases such as chronic rheumatoid arthritis; therapeutic agents for autoimmune diseases such as ulcerative colitis and nephritis; and as anti-AIDS drugs.
Abstract: The present invention relates to optically pure 8-(substituted piperidino)-benzo[i,j]quinolizines, their isomers, derivatives, salts, pseudopolymorphs, polymorphs prodrugs and hydrates thereof, to processes for their preparation, and to pharmaceutical compositions comprising 8-(substituted piperidino)-benzo[i,j]quinolizines their isomers, derivatives, salts, pseudopolymorphs, polymorphs and hydrates thereof. These compounds and compositions possess potent activity in treating local and systemic infections, particularly infections caused by sensitive and resistant Gram-positive organism infections, Gram-negative organism infections, mycobacterial infections and nosocomial pathogens, and particularly those belonging to the staphylococcus, streptococcus and enterococcus groups. Methods for treating the diseases and disorders arising from the foregoing infections in humans and animals are described by administering the compounds of the invention to said humans and animals.
Type:
Application
Filed:
May 7, 2001
Publication date:
November 7, 2002
Applicant:
WOCKHARDT RESEARCH CENTER
Inventors:
Noel John De Souza, Mahesh Vithalbhai Patel, Shiv Kumar Agarwal, Shirkant V. Gupte, Dilip J. Upadhyay, Satish B. Bhawsar, Mohammad A. Jafri
Abstract: Compounds of formula (I), in which R1, R2, R3, R31, R4, R5, R51, R6, R13 and R20 have the meaning indicated in the description, are novel active bronchial therapeutics
Abstract: Non-peptide compounds that act as antagonists of the intestinal hormone glucagons-like peptide 1 (GLP-1) have a 9H-b-carboline central motif. The compounds exhibit advantageous physical, chemical and biological properties and inhibit GLP-1 peptide binding to the GLP-1 receptor and/or prevent activation of the receptor by bound GLP-1. The invention further relates to a method of inhibiting the binding of GLP-1 to the GLP-1 receptor and a method of inhibiting the activation of the GLP-1 receptor. Intermediate compounds useful for making non-peptide GLP-1 receptor antagonists are also described.
Type:
Grant
Filed:
October 26, 2001
Date of Patent:
October 22, 2002
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Larry Kenneth Truesdale, Richard A. Bychowski, Javier Gonzalez, Atsuo Kuki, Ranjan Jagath Rajapakse, Min Teng, Dan Kiel, Daljit S. Dhanoa, Yufeng Hong, Tso-sheng Chou, Anthony L. Ling, Michael David Johnson, Vlad Edward Gregor
Abstract: Compounds of general structural formula (I) wherein A represents a 5- or 6-membered heteroaryl group containing at least one heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur, and use of the compounds, and salts and solvates thereof, as therapeutic agents, are disclosed.
Abstract: The present invention relates to a method for the preparation for camptothecin and camptothecin-like compounds and to novel intermediates used in this preparation. In particular, the invention provides a process for the preparation of the camptothecin derivative of formula (I′) known by the chemical name “7-(4-methylpiperazino-methylene)-10,11-ethylenedioxy-20(R,S)-camptothecin”, which comprises cyclising the compound of formula (II′), wherein X is halogen, particularly chloro, bromo, or iodo; and when the compound of formula (I′) is obtained as a mixture of enantiomers optionally resolving the mixture to obtain the desired enantiomer; and/or if desired, converting the resulting compound of formula (I′) or a salt thereof into a physiologically acceptable salt or solvate thereof.
Type:
Grant
Filed:
April 19, 2000
Date of Patent:
October 8, 2002
Assignee:
OSI Pharmaceuticals, Inc.
Inventors:
Francis Gerard Fang, Edward McDonald Huie, Shiping Xie, Daniel L. Comins
Abstract: Benzo[f]naphthyridine derivatives of formula (I): 1
Type:
Application
Filed:
December 31, 2001
Publication date:
September 26, 2002
Inventors:
Jean-Francois Desconclois, Arielle Genevois-Borella, Philippe Girard, Michel Kryvenko, Marc Pierre Lavergne, Jean-Luc Malleron, Guy Picaut, Michel Tabart, Sylvie Wentzler
Abstract: The present invention provides 1,4 substituted piperazines, 1,4 substituted piperidines, and 1-substituted, 4-alkylidenyl peperidines compounds. The compounds of the invention are dual acting molecules having both leukotriene inhibition properties as well as antihistaminergic properties. The compounds of the invention are useful for treating conditions in which there is likely to be a histamine and/or leukotriene component. These conditions include preferable asthma, seasonal and perennial allergic rhinitis, sinusitus, conjunctivitis, food allergy, scombroid poisoning, psoriasis, urticaria, pruritus, eczema, rheumatoid arthritis, inflammatory bowel disease, chronic obstructive pulmonary disease, thrombotic disease and otitis media. Also provided are methods of treating asthma and rhinitis by administering an effective asthma and rhinitis-relieving amount of the compounds to a subject in need thereof.
Type:
Grant
Filed:
March 24, 2000
Date of Patent:
September 17, 2002
Assignee:
UCB, S.A.
Inventors:
Ralph Scannell, Pierre Chatelain, Anna Toy-Palmer, Edmond Differding, James Ellis, Marie-Agnes Lassoie, Xiong Cai, Sajjat Hussoin, Gurmit Grewal, Timothy Lewis
Abstract: Disclosed are compounds of the formula:
or the pharmaceutically acceptable non-toxic salts thereof where R1-R4 and A are defined herein, 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 and are, therefore, useful in the diagnosis and treatment of anxiety, Down Syndrome, depression, sleep, cognitive and seizure disorders, overdose with benzodiazepine drugs and for enhancement of alertness.
Abstract: Compounds of formula I
wherein G, J, L, M, m and D have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.
Abstract: Novel halo-N-substituted urea compounds and pharmaceutical compositions are disclosed which are inhibitors of the enzyme, farnesyl protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel halo-N-substituted urea compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammals such as a human.
Abstract: Novel compounds of the formula:
are disclosed. In Formula 1.0 a represents N or NO, R1 and R3 are halo, R2 and R4 are independently H or halo provided that at least one is H, X is C, CH or N, and T represents a five or six membered heterocycloalkyl ring having one or two heteroatoms selected from S or O.
Also disclosed are methods of inhibiting farnesyl protein transferase and methods for treating tumor cells.
Type:
Grant
Filed:
February 20, 2001
Date of Patent:
August 27, 2002
Assignee:
Schering Corporation
Inventors:
Ronald J. Doll, Carmen Alvarez, Tarik Lalwani, Yi-Tsung Liu
Abstract: Novel phenyl-substituted tricyclic compounds and pharmaceutical compositions are disclosed which are inhibitors of the enzyme, farnesyl protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel halo-N-substituted urea compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammals such as a human.
Type:
Grant
Filed:
February 13, 2001
Date of Patent:
August 27, 2002
Assignee:
Schering Corporation
Inventors:
Adriano Afonso, Joseph M. Kelly, Jay Weinstein, Ronald L. Wolin, Stuart B. Rosenblum
Abstract: Disclosed are compounds of the formula: 1
Type:
Application
Filed:
December 20, 2001
Publication date:
August 1, 2002
Inventors:
Arthur G. Taveras, Ronald J. Doll, Alan B. Cooper, Johan A. Ferreira, Timothy Guzi, Alan K. Mallams, Dinanath F. Rane, Viyyoor M. Girijavallabhan, Adriano Afonso, Cynthia J. Aki, Jianping Chao, Carmen Alvarez, Joseph M. Kelly, Tarik Lalwani, Jagdish A. Desai, James J-S Wang, Jay Weinstein
Abstract: Novel tricyclic sulfonamide compounds and pharmaceutical compositions are disclosed which are inhibitors of the enzyme, farnesyl protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel sulfonamide compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammals such as a human.
Type:
Grant
Filed:
August 13, 1999
Date of Patent:
July 30, 2002
Assignee:
Schering Corporation
Inventors:
F. George Njoroge, Bancha Vibulbhan, Arthur G. Taveras, Ronald J. Doll, Viyyoor M. Girijavallabhan
Abstract: This invention relates to novel multibinding compounds (agents) that are H1 histamine receptor antagonists and pharmaceutical compositions comprising such compounds. Accordingly, the multibinding compounds and pharmaceutical compositions of this invention are useful in the treatment and prevention of allergic diseases such as rhinitis, urticaria, asthma, and anaphylaxis, and the like.
Type:
Grant
Filed:
June 7, 1999
Date of Patent:
July 16, 2002
Assignee:
Theravance, Inc.
Inventors:
Robert P. Numerof, Yu-Hua Ji, John H. Griffin
Abstract: The present invention discloses novel substituted imidazole compounds which have dual histamine-H1 and H3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy, inflammatory and CNS-related diseases and others.
Type:
Application
Filed:
September 18, 2001
Publication date:
July 4, 2002
Inventors:
Neng-Yang Shih, Daniel M. Solomon, John J. Piwinski, Andrew T. Lupo, Michael J. Green
Abstract: Novel compounds of the formula:
are disclosed. In Formula 1.0 a represents N or NO, R1 and R3 are halo, R2 and R4 are independently H or halo provided that at least one is H, X is C, CH or N, and R represents a cycloalkyl or a heterocycloalkyl ring that is substitued.
Also disclosed are methods of inhibiting farnesyl protein transferase and methods for treating tumor cells.
Type:
Grant
Filed:
January 24, 2001
Date of Patent:
June 25, 2002
Assignee:
Schering Corporation
Inventors:
Stacy W. Remiszewski, Ronald J. Doll, Carmen Alvarez, Tarik Lalwani
Abstract: Compounds of the formula
and their pharmaceutically acceptable salts, wherein R1, R2, and R3 are defined as in the specification, intermediates in the synthesis of such compounds. pharmaceutical compositions containing such compounds and methods of using such compounds, in the treatment of neurological and psychological disorders.
Abstract: A 6,13-dihydroquinacridone derivative of formula I:
(MO3S)m—Q—[CH2—(X)—(Y)n]o (I)
wherein:
Q represents a 6,13-dihydroquinacridone moiety of formula II;
A and B each independently represent a substituent selected from H, F, Cl, C1-C3alkyl and C1-C3alkoxy
M represents a metal cation, quaternary N cation or H;
X is an aromatic group, a cyclo-hetero aliphatic group with at least one 5 or 6 atom ring or a hetero aromatic group with at least one 5 or 6 atom ring and which is not a phthalimido group;
Y is a sulfonic or carboxylic acid or salt thereof;
m and n independently from each other are numbers from zero to 2.5; and o is a number from zero to 4, wherein m and o are not zero simultaneously.
Abstract: Disclosed are 1-Azatricyclic-4-benzylpiperazine compounds which are useful for the treatment and/or prevention of neuropsychological disorders including, but not limited to, schizophrenia, mania, dementia, depression, anxiety, compulsive behavior, substance abuse, Parkinson-like motor disorders and motion disorders related to the use of neuroleptic agents. Pharmaceutical compositions, including packaged pharmaceutical compositions, are further provided. Compounds of the invention are also useful as probes for the localization of GABAA receptors in tissue samples.
Type:
Grant
Filed:
June 28, 2001
Date of Patent:
June 11, 2002
Assignee:
Neurogen Corporation
Inventors:
Kevin Hodgetts, Stanislaw Rachwal, Daniel Rosewater, Andrew Thurkauf, Xiaoyan Zhang
Abstract: Novel compounds of the formula:
wherein a represents N or NO, R1 and R3 are halo, R2 and R4 are independently H or halo provided that at least one is H, X is C, CH or N, and T represents
wherein R5 is H (C1-C6)alkyl or a bond; b and c are independently 0 to 3 and Y is a three, four, five or six membered cycloalkyl ring, pyridyl, pyrazinyl or phenyl are disclosed. Pharmaceutical Compositions containing such compounds, methods of inhibiting farnesyl protein transferase and methods for treating tumor cells using such compounds or compositions are also disclosed.
Abstract: Novel compounds of the formula:
are disclosed. Compounds of Formula 1.0 are represented by the compounds of formulas:
wherein R1, R3 and R4 are each independently selected from halo.
Also disclosed are methods of inhibiting farnesyl protein transferase and the growth of abnormal cells, such as tumor cells.
Type:
Grant
Filed:
March 1, 2001
Date of Patent:
May 14, 2002
Assignee:
Schering Corporation
Inventors:
F George Njoroge, Arthur G. Taveras, Ronald J. Doll, Tarik Lalwani, Carmen Alvarez, Stacy W. Remiszewski
Abstract: Disclosed are compounds of the formula:
wherein R13 represents an imidazole ring; R14 represents a carbamate, urea, amide or sulfonamide group; R8 represents H when the alkyl chain between the amide group and the R13 imidazole group is substituted, or R8 represents a substituent such as arylalkyl, heteroarylalkyl or cycloalkyl; and the remaining substituents are as defined herein. Also disclosed are compounds wherein R8 is H, and the alkyl chain between the amide group and the R13 imidazole group is unsubstituted. Also disclosed is a method of treating cancer and a method of inhibiting farnesyl protein transferase using the disclosed compounds.
Type:
Grant
Filed:
December 16, 1999
Date of Patent:
April 16, 2002
Assignee:
Schering Corporation
Inventors:
Arthur G. Taveras, Ronald J. Doll, Alan B. Cooper, Johan A. Ferreira, Timothy Guzi, Dinanath F. Rane, Viyyoor M. Girijavallabhan, Cynthia J. Aki, Jianping Chao, Carmen Alvarez, Joseph M. Kelly, Tarik Lalwani, Jagdish A. Desai, James J-S Wang
Abstract: A method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells is disclosed. The method comprises the administration of a compound of Formula 1.0:
to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human being.
Novel compounds of the formulas 5.0, 5.1 and 5.2, wherein R is —C(R20)(R21)(R46), and 5.3, 5.3A and 5.3B, wherein R is —N(R25)(R48), are disclosed.
Also disclosed are processes for making 3-substituted compounds of Formulas 5.0, 5.1, 5.2 and 5.3.
Further disclosed are novel compounds which are intermediates in the process for making 3-substituted compounds of Formulas 5.0, 5.1, 5.2 and 5.3.
Type:
Grant
Filed:
July 9, 1999
Date of Patent:
April 2, 2002
Assignee:
Schering Corporation
Inventors:
Robert W. Bishop, Ronald J. Doll, Alan K. Mallams, F. George Njoroge, Joanne M. Petrin, John J. Piwinski, Ronald L. Wolin, Arthur G. Taveras, Stacy W. Remiszewski
Abstract: Disclosed are compounds of the formula:
wherein R8 represents a cyclic moiety to which is bound an imodazolylalkyl group; R9 represents a carbamate, urea, amide or sulfonamide group; and the remaining substituents are as defined herein. Also disclosed is a method of treating cancer and a method of inhibiting farnesyl protein transferase using the disclosed compounds.
Type:
Grant
Filed:
December 16, 1999
Date of Patent:
March 26, 2002
Assignee:
Schering Corporation
Inventors:
Timothy Guzi, Dinanath F. Rane, Alan K. Mallams, Alan B. Cooper, Ronald J. Doll, Viyyoor M. Girijavallabhan, Arthur G. Taveras, Corey Strickland, Joseph M. Kelly, Jianping Chao
Abstract: Disclosed are compounds of the formula:
wherein Ar, R1, W and X are substituents as defined herein,
which compounds are (1) antagonists at CRF1 receptors and are, therefore, useful in the diagnosis and treatment of stress related disorders such as post traumatic stress disorder (PTSD) as well as depression, headache and anxiety; and (2) are neuropeptide Y1, receptor antagonists, and are therefore useful in the treatment of a variety of clinical conditions which are characterized by the presence of an excess of neuropeptide Y.
Type:
Grant
Filed:
November 6, 2000
Date of Patent:
March 26, 2002
Assignee:
Neurogen Corporation
Inventors:
Raymond F. Horvath, James W. Darrow, George D. Maynard
Abstract: Fluorescent compounds of the formula:
wherein R1 and R2 are either both SO3M, or one of R1 and R2 is SO3M and the other is COOM, where M is selected from the group consisting of H, Na, K, Rb, Cs, Li or ammonium, are described and claimed. These inert flurorescent compounds have been found to be resistant to oxidizing biocides. One process for making these compounds is described and claimed as the condensation between a 1,8-naphthalic anhydride possessing the desired functionalities and the appropriately substituted o-phenylene diamine. Alternatively, o-amino-nitro-aromatics may be condensed with the various 1,8-naphthalic anhydrides when the in situ reduction of the nitro group is accomplished with a suitable reducing agent such as iron powder. The resulting fluorescent compounds can be used as inert fluorescent tracers in industrial water systems.
Type:
Grant
Filed:
November 8, 1999
Date of Patent:
March 19, 2002
Assignee:
Nalco Chemical Company
Inventors:
Barbara E. Moriarty, Jerry L. Reddinger
Abstract: A C-6 ring-substituted pyrido[1,2-a]benzimidazole derivative of the formula:
methods of preparation and pharmaceutical compositions containing a substituted pyrido[1,2-a]benzimidzole derivative as the active ingredient are disclosed. The substituted pyrido[1,2-a]benzimidazole derivatives are useful in the treatment of central nervous system disorders.
Type:
Grant
Filed:
July 20, 2000
Date of Patent:
March 19, 2002
Assignee:
Ortho-McNeil Pharmaceutical, Inc.
Inventors:
Allen B. Reitz, Samuel O. Nortey, Pauline Sanfilippo, Malcolm K. Scott
Abstract: Heteroarylpiperidines, pyrrolidines, and piperazines are useful as antipsychotic and analgesic agents. The compounds are especially useful for treating psychoses by administering to a mammal a psychoses-treating effective amount of one of the compounds. Depot derivatives of the compounds are useful for providing long acting effects of the compounds. The compounds are also useful as analgesics by administering a pain-relieving effective amount of one of the compounds to a mammal.
Type:
Grant
Filed:
February 3, 1999
Date of Patent:
June 4, 2002
Assignee:
Aventis Pharmaceuticals Inc.
Inventors:
Edward J. Glamkowski, Yulin Chiang, Joseph T. Strupczewski, Kenneth J. Bordeau, Peter A. Nemoto, John J. Tegeler