Abstract: This invention provides a process for conducting Suzuki coupling reactions. The processes of the present invention make use of N-heterocyclic carbenes as ancillary ligands in Suzuki couplings of aryl halides and aryl pseudohalides. A Suzuki coupling can be carried out by mixing, in a liquid medium, at least one strong base; at least one aryl halide or aryl pseudohalide in which all substituents are other than boronic acid groups, wherein the aryl halide has, directly bonded to the aromatic ring(s), at least one halogen atom selected from the group consisting of a chlorine atom, a bromine atom, and an iodine atom; at least one arylboronic acid in which all substituents are other than chlorine atoms, bromine atoms, iodine atoms, or pseudohalide groups; at least one metal compound comprising at least one metal atom selected from nickel, palladium, and platinum, wherein the formal oxidation state of the metal is zero or two; and at least one N-heterocyclic carbene.
Type:
Grant
Filed:
February 22, 2000
Date of Patent:
June 11, 2002
Assignee:
University of New Orleans Research & Technology
Foundation
Inventors:
Steven P. Nolan, Jinkun Huang, Mark L. Trudell, Chunming Zhang
Abstract: This invention provides a process for conducting amination reactions. The processes of the present invention make use of N-heterocyclic carbenes as ancillary ligands in aminations of aryl halides and aryl pseudohalides. An amination can be carried out by mixing, in a liquid medium, at least one strong base; at least one aryl halide or aryl pseudohalide in which all substituents are other than amino groups, wherein the aryl halide has, directly bonded to the aromatic ring(s), at least one halogen atom selected from the group consisting of a chlorine atom, a bromine atom, and an iodine atom; at least one primary amine and/or at least one secondary amine; at least one metal compound comprising at least one metal atom selected from nickel, palladium, and platinum, wherein the formal oxidation state of the metal is zero or two; and at least one N-heterocyclic carbene.
Type:
Grant
Filed:
February 22, 2000
Date of Patent:
June 11, 2002
Assignee:
University of New Orleans Research & Technology
Foundation
Inventors:
Steven P. Nolan, Jinkun Huang, Mark L. Trudell, Chunming Zhang
Abstract: The invention disclosed herein relates to the preparation of pharmaceutical grades of histamine dihydrochloride using a two step non-enzymatic synthetic method. The invention disclosed herein describes the synthesis of histamine dihydrochloride by the non-enzymatic decarboxylation of histidine and the step-wise conversion of the decarboxylated product to the dihydrochloride salt form. The invention disclosed herein considers a final product of histamine dihydrochloride containing less than each of the following: 0.8% L-histidine HCl monohydrate, 0.1% individual chromatographic impurities, and 2% total impurities, to be acceptable for pharmaceutical use.
Type:
Grant
Filed:
December 20, 1999
Date of Patent:
June 11, 2002
Assignee:
Maxim Pharmaceuticals, Inc.
Inventors:
Wen-Lung Yeh, Casimir Antczak, Jeffry David McGolrick, Michael Joseph Roth, Mark Wrona
Abstract: This invention relates to novel xanthone compounds, their preparation and use as medicament. More particularly this invention is directed to the isolation of the novel xanthone natural product sootepenseone from Dasymaschalon sootepense Craib, Annonaceae, its identification and derivatization, and the use of sootepenseone and its derivatives as anticancer agents.
Type:
Grant
Filed:
June 28, 2000
Date of Patent:
June 11, 2002
Assignee:
Zentaris AG
Inventors:
Vichai Reutrakul, Thaiwatchai Santisuk, Gerhard Noessner, Juergen Schmidt, Bernd Nickel, Thomas Klenner, Sebastian Hose
Abstract: The invention relates to a compound having formula (I) wherein A is an optionally unsaturated 5- or 6-membered ring, which may comprise a heteroatom selected from N,O and S and which may be substituted with oxo or (1-6C) alkyl; R1, R2 and R3 are independently H, (1-6C) alkyl, (1-6C) alkoxy,(1-6C) alkoxy-(1-6C) alkyl, carbo(1-6C) alkoxy or halogen; X is O or S; and n is 1 or 2; or a pharmaceutically acceptable salt thereof, with the exception of 3-(naphth-1-yl-oxy)-pyrrolidin and 3-(5,6,7,8-tetrahydro-napth-1-yl-oxy)-pyrrolidin. The compounds of the invention have antidepressant activity and can be used in treating or preventing serotonin-related diseases.
Type:
Grant
Filed:
May 30, 2001
Date of Patent:
June 11, 2002
Assignee:
Akzo Nobel N.V.
Inventors:
Dirk Leysen, Johannes Hubertus Wieringa, Christophorus Louis Eduard Broekkamp
Abstract: The present invention is related to:
(i) matrix metalloproteinase inhibitors containing sulfonylamino acid derivatives of the formula (Ia);
wherein R1 is hydrogen, C1-4 alkyl; R2 is hydrogen, C1-8 alkyl etc.; E is —CONR3—, in which R3 is hydrogen, C1-4 alkyl etc., —NR3CO—, —CO—O—, —O—CO— etc.; A is hydrogen, C1-8 alkyl, C3-7 cycloalkyl, or Ar; J is bond, C2-4 alkylene etc.; G is —
(CH2)m—, in which m is 2, 3 or 4, or
in which R6 and R7 is hydrogen, C1-8 alkyl etc.; and non-toxic salts thereof,
(ii) sulfonylamino acid derivatives of the formula (Ib):
wherein all the symbols are the same meaning as (i); and non-toxic salts thereof, and
(iii) process for the preparation of the compound of the formula (Ib).
The compounds of the formula (Ia) are useful for prevention and/or treatment of diseases induced by overexpression and excess activity of MMP.
Abstract: A compound of the formula
wherein
R1 is C1-3 alkyl optionally substituted with one or more fluorines;
R2 is C1-6 alkyl, cycloalkyl or NR4R5;
R3 is a pyrazole, imidazole or isoxazole group of partial formula (A), (B) or (C)
NR4R5 is a nitrogen-containing heterocyclic ring;
R6 is C1-3 alkyl; and
R7 and R8, which are the same or different, each represents C1-3 alkyl, halogen, CF3 or CN;
or a pharmaceutically-acceptable salt thereof.
Type:
Grant
Filed:
February 9, 2001
Date of Patent:
June 11, 2002
Assignee:
Darwin Discovery, Ltd.
Inventors:
Hazel Joan Dyke, Alan Findlay Haughan, Christopher Lowe, George Martin Buckley, Richard John Davenport, Andrew Sharpe, Hannah Jayne Kendall, Verity Margaret Sabin, John Gary Montana, Catherine Louise Picken
Abstract: Compounds which have enhanced affinity and selectivity for 5-HT6 receptors have been identified. These compounds can be used therapeutically in the treatment of mental disorders via administration in a pharmacologically acceptable delivery route to a patient in need thereof, or can be used to identify antagonists of 5-HT6 receptors by well known screening methodologies which could themselves be used in the treatment of mental disorders.
Abstract: A process for producing a binaphthol bistriflate, 2,2′-bis(trifluoromethanesulfonyloxy)-1,1′-binaphthyl, includes reacting 1,1′-bi-2-naphthol with trifluoromethanesulfonyl fluoride, in a polar solvent, in the presence of an organic base. The reaction proceeds quickly at a low temperature by using a polar solvent as the reaction solvent, while the reaction pressure does not become high. The polar solvent is preferably at least one selected from N,N-dimethylformamide, N,N-dimethylacetoamide, 1-methyl-2-pyrrolidinone, and acetonitrile.
Abstract: The present invention relates to processes for the conversion of nitrites to amidines in the preparation of compounds which are antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex. The compounds described herein are potent thrombolytics and useful for the inhibition of platelet aggregation in the treatment of thromboembolic disorders.
Type:
Grant
Filed:
January 10, 2001
Date of Patent:
June 4, 2002
Assignee:
Bristol-Myers Squibb Pharma Company
Inventors:
Philip Ma, Pasquale N. Confalone, Hui-Yin Li
Abstract: Compounds having Formula 1 wherein the symbols have the meaning defined in the specification are inhibitors of the cytochrome P450RAI (retinoic acid inducible) enzyme, and are used for treating diseases responsive to treatment by retinoids.
Type:
Grant
Filed:
April 9, 2001
Date of Patent:
June 4, 2002
Assignee:
Allergen Sales, Inc.
Inventors:
Jayasree Vasudevan, Alan T. Johnson, Dehua Huang, Roshantha A. Chandraratna
Abstract: The present invention relates to novel nodulosporic acid derivatives, which are acaricidal, antiparasitic, insecticidal and anthelmintic agents.
Type:
Grant
Filed:
July 9, 2001
Date of Patent:
June 4, 2002
Assignee:
Merck & Co., Inc.
Inventors:
Steven L. Colletti, Michael H. Fisher, Peter T. Meinke, Matthew J. Wyvratt
Abstract: The invention relates to novel cyclic imines of the formula (I)
in which
Ar1 and Ar2 each represent substituted phenyl and n represents 1, 2 and 3, to a plurality of processes for their preparation and to their use as pesticides.
Type:
Grant
Filed:
September 9, 2000
Date of Patent:
June 4, 2002
Assignee:
Bayer Aktiengesellschaft
Inventors:
Andrew Plant, Gerd Kleefeld, Thorsten Pötter, Christoph Erdelen, Norbert Mencke, Andreas Turberg, Ulrike Wachendorff-Neumann
Abstract: The invention is directed to multiply-substituted fullerene derivatives of novel configurations, and methods for their preparation and use. The methods involve the combinatorial synthesis of a library of fullerene derivatives and comprises the steps of forming a mixture of fullerene derivatives by reacting the Cn fullerene with two or more reactive precursor compounds, and removing the unreacted compounds to yield the fullerene derivatives having the desired activity. Methods for the identification and screening of a combinatorial library of fullerenes by 3He-nuclear magnetic resonance and electrospray mass spectrometry to define members with the optimal desired activity are also provided.
Type:
Grant
Filed:
October 30, 2000
Date of Patent:
June 4, 2002
Assignee:
C-Sixty, Inc.
Inventors:
Randall B. Murphy, Stephen R. Wilson, Quing Lu
Abstract: This invention provides an improved process for cis-1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy]ethyl}pyrrolidine which is an intermediate for the preparation of (−)cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydronaphthalene-2-ol which is useful for the treatment of osteoporosis.
Abstract: Disclosed are cathepsin S reversible inhibitory compounds of the formulas (I),(Ia) and (II),(IIa) as defined herein. The compounds are useful for treating autoimmune diseases. Also disclosed are processes for making such novel compounds.
Type:
Grant
Filed:
November 5, 1999
Date of Patent:
May 28, 2002
Assignee:
Boehringer Ingelheim Pharmaceuticals, Inc.
Inventors:
Charles L. Cywin, Michel J. Emmanuel, Leah L. Frye, Denice M. Spero, David S. Thomson, Yancey D. Ward
Abstract: One aspect of the present invention relates to novel, electron-rich bidentate ligands for transition metals. A second aspect of the present invention relates to the use of catalysts comprising these ligands in transition metal-catalyzed carbon-heteroatom and carbon-carbon bond-forming reactions. The subject methods provide improvements in many features of the transition metal-catalyzed reactions, including the range of suitable substrates, reaction conditions, and efficiency.
Type:
Grant
Filed:
July 10, 1998
Date of Patent:
May 28, 2002
Assignee:
Massachusetts Institute of Technology
Inventors:
Stephen L. Buchwald, John P. Wolfe, David W. Old, Ken Kamikawa, Michael Palucki
Inventors:
Pradip Kumar Bhatnagar, Joelle Lorraine Burgess, James Francis Callahan, Raul Rolando Calvo, Eric G. Del Mar, Maria Amparo Lago, Thomas The Nguyen
Abstract: 4-oxo-tetrahydroindozole-3-carboxamide compounds according to Formula (I), or a pharmaceutically acceptable salt thereof, are GABA-A Alpha 5 ligands useful for enhancing cognition:
Type:
Grant
Filed:
June 15, 2001
Date of Patent:
May 28, 2002
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Helen Jane Bryant, Mark Stuart Chambers
Abstract: The subject-matter of the invention is a process for the preparation of o-(p-tolyl)benzonitrile, characterized in that an o-halobenzonitrile is treated with a p-tolylmagnesium halide in the presence of a manganous salt and of a cocatalyst comprising a transition metal.
Type:
Grant
Filed:
June 30, 1999
Date of Patent:
May 21, 2002
Assignee:
Sanofi-Stnth{dot over (e)}labo
Inventors:
Mouad Alami, Gérard Cahiez, Bertrand Castro, Eric Riguet