Abstract: Disclosed are compounds which are neurokinin (tachykinin)-antagonists, useful for the treatment or prevention of inflammatory and allergic disease.
Type:
Grant
Filed:
December 1, 1999
Date of Patent:
May 15, 2001
Assignee:
Boehringer Ingelheim KG
Inventors:
Franz Esser, Gerd Schnorrenberg, Hans-Peter Ignatow, Günther Giesler, Birgit Jung, Georg Speck
Abstract: Novel aromatic heterocyclic compounds inhibit cytokines production involved in immunoregulation and inflammation such as interleukin-1 and tumor necrosis factor production. The compounds are therefore useful in pharmaceutic compositions for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases.
Type:
Grant
Filed:
December 14, 1999
Date of Patent:
May 8, 2001
Assignee:
Boehringer Ingelheim Pharmaceuticals, Inc.
Inventors:
John R. Regan, Pier F. Cirillo, Eugene R. Hickey, Neil Moss, Charles L. Cywin, Christopher Pargellis, Thomas A. Gilmore
Abstract: Hard shelled capsules and dry, powdered pharmaceutical formulations are treated with supercritical fluids to remove impurities such as mold lubricants and moisture.
Type:
Grant
Filed:
September 21, 1998
Date of Patent:
May 8, 2001
Assignee:
Boehringer Ingelheim Pharmaceuticals, Inc.
Abstract: A compound of formula I:
wherein R1 is hydrogen, methyl, ethyl, methoxy or methylthio; R2 and R3 each independently is hydrogen or C1-3 alkyl; R4 is hydrogen, lower alkyl, methoxy, ethoxy, or benzyloxy; R5 is lower alkyl, lower cycloalkyl, (CH2)mC(O)OR6 wherein m is the integer 1 or 2 and R6 is lower alkyl, phenyl optionally substituted with C(O)OR7 wherein R7 is lower alkyl or phenyl (lower alkyl); or R6 is Het or Het(lower alkyl; or R4 and R5 together with the nitrogen atom to which they are attached form a nitrogen containing ring optionally substituted with benzyloxycarbonyl or with phenyl optionally substituted among other group with C(O)OR7 wherein R7 is lower alkyl or (lower alkyl)phenyl; X is selected from the group consisting of O, S, SO, SO2, NR8, wherein R8 is H or lower alkyl; and
Y is C1-10 non-cyclic or cyclic alkyl; [(CH2)0-1]-phenyl, said phenyl ring optionally substituted; Het or Het(lower alkyl); or when X is NR8, wherein R8 is lower alkyl and Y is lower alkyl or
Type:
Grant
Filed:
October 6, 1998
Date of Patent:
April 3, 2001
Assignee:
Boehringer Ingelheim (Canada) Ltd.
Inventors:
Christiane Yoakim, Robert Déziel, Stephen Kawai, William W. Ogilvie, Jeffrey O'Meara, Catherine Chabot
Abstract: Quinoxazolines having antithrombotic activity. Exemplary of those disclosed are:
4-{[6-(N-carboxymethyl-quinolin-8-yl-sulphonylamino)-1-methyl-2-oxo-1,2-dihydroquinoxalin-3-yl]-methyl}-benzamidine,
4-{[6-(1-(N-cyclopentyl-carboxymethylcarbonylamino)-cyclo-propyl)-1-methyl-2-oxo-1,2-dihydroquinoxalin-3-yl]-methyl}-benzamidine, and
4-{[7-(N-carboxymethylaminocarbonyl-ethylamino)-4-methyl-quinolin-2-yl]-oxo}-benzamidine.
Type:
Grant
Filed:
March 29, 1999
Date of Patent:
March 13, 2001
Assignee:
Boehringer Ingelheim Pharma KG
Inventors:
Uwe Ries, Norbert Hauel, Henning Priepke, Herbert Nar, Jean Marie Stassen, Wolfgang Wienen
Abstract: Pyranoside derivatives of the formula I
wherein 1, m and n independently of one another denote an integer chosen from 0, 1, 2, 3 and 4 and 1+m+n≦4. These are are LTB4-antagonists. Also disclosed are processes for making these compounds.
Type:
Grant
Filed:
March 8, 1999
Date of Patent:
March 6, 2001
Assignee:
Boehringer Ingelheim KG
Inventors:
Ralf Anderskewitz, Kurt Schromm, Ernst-Otto Renth, Franz Birke, Hans M. Jennewein, Christopher J. M. Meade, Andreas Ding
Abstract: Human cytomegalovirus (HCMV) protease is a slow-processing enzyme in vitro. Disclosed herein are improved fluorogenic and radiometric peptide substrates for CMV protease. The improved substrates have a Tbg-Tbg-Asn(NMe2) sequence replacing the Val-Val-Asn sequence, corresponding to the P4-P2 residues of the maturation site of the enzyme. The incorporation of this new sequence in a variety of substrates has afforded substrates with improved kinetic parameters compared to homologues containing the natural sequence only. For example, the substrate 2-aminobenzoyl-Tbg-Tbg-Asn(NMe2)-AlaiSer-Ser-Arg-Leu-Tyr(3-NO2)ARG-OH displayed a kcat/Km value of 15940 M-−1—s−1, i.e. over 60-fold greater than that of the equivalent, non-optimized substrate in identical conditions. The new substrates find use in assays which can evaluate and characterize HCMV protease inhibitors having low nanomolar potency.
Abstract: The invention relates to new compounds of general formula
and the pharmaceutically acceptable salts thereof, wherein A, B, Z, R1, R2, R3 and m are defined as in the specification, processes for preparing them and pharmaceutical compositions containing these compounds. The compounds are valuable neurokinin (tachykinin) antagonists.
Type:
Grant
Filed:
February 8, 2000
Date of Patent:
February 20, 2001
Assignee:
Boehringer Ingelheim KG
Inventors:
Horst Dollinger, Gerd Schnorrenberg, Hans Briem, Birgit Jung, Georg Speck
Abstract: The present invention relates to an improved process for preparing L-phenylephrine hydrochloride 3 on an industrial scale by asymmetric hydrogenation as the key step and a special sequence of subsequent steps, using [Rh(COD)Cl]2 as catalyst and a chiral, two-pronged phosphine ligand such as (2R,4R)-4-(dicyclohexylphosphino)-2-(diphenylphosphino-methyl)-N-methyl-aminocarbonyl-pyrrolidine as the catalyst system.
Type:
Grant
Filed:
January 19, 2000
Date of Patent:
February 13, 2001
Assignee:
Boehringer Ingelheim Pharma KG
Inventors:
Franz Dietrich Klinger, Lienhard Wolter, Wolfgang Dietrich
Abstract: Asymmetrically substituted xanthine derivatives having adenosine A1 antagonistic activity. These are useful as pharmaceuticals. Exemplary are:
(a) 3-(2-(2-acetyloxyethyl)sulphonylethyl)-8-(1-noradamantyl)-1-n-propyl-xanthine;
(b) 3-(2-(hydroxyethyl)sulphonylethyl)-8-(1-noradamantyl)-1-n-propyl-xanthine; and,
(c) 3-(2-(carbamoylethyl)-8-(1-noradanantyl)-1-n-propyl-xanthine.
Type:
Grant
Filed:
April 7, 1999
Date of Patent:
February 13, 2001
Assignee:
Boehringer Ingelheim Pharma KG
Inventors:
Stefan Blech, Adrian Carter, Wolfram Gaida, Ursula Gath, Matthias Hoffmann, Ulrike Kuefner-Muehl, Erich Lehr, Joachim Mierau, Gerald Pohl, Thomas Weiser
Abstract: The present invention relates to orally administered suspensions of pharmaceutical active substances of the NSAID type, particularly the antirheumatic agent Meloxicam, which are stabilized by the addition of small amounts of highly dispersed silicon dioxide using high shear forces and adding small amounts of hydrophilic polymers to form a three-dimensional siloid structure, and a process for the preparation thereof.
Abstract: A compound of formula I
wherein
A denotes a benzo, indolo or thieno group;
R1 denotes thienyl or the group
wherein
R7, R8 and R9 independently of one another may represent methyl, ethyl, propyl, phenyl or benzyl, while not more than 2 of the substituents can simultaneously represent phenyl or benzyl;
R2, m, R3 and R4 are defined as in the specification, as well as pharmaceutical preparations containing this compound and the new pharmaceutical uses thereof.
Type:
Grant
Filed:
February 18, 1999
Date of Patent:
January 30, 2001
Assignee:
Boehringer Ingelheim GmbH
Inventors:
Walter Lösel, Otto Roos, Dietrich Arndts
Abstract: An aqueous pharmaceutical suspension consisting essentially of nevirapine hemihydrate having a particle size between about 1 and 150 microns in diameter.
Type:
Grant
Filed:
August 11, 1998
Date of Patent:
January 9, 2001
Assignee:
Boehringer Ingelheim Pharmaceuticals, Inc.
Abstract: Disclosed are compositions containing compounds of the formula (I) below wherein A,B,C,G,Q and R are defined herein. The compounds are useful as phosphotyrosine mimics that, when incorporated into an appropriate molecular structure, inhibit the binding of tyrosine kinase-dependent regulatory proteins to their native phosphotyrosine-containing ligands or receptors. Also disclosed are methods for preparing the compounds of the formula (I).
Type:
Grant
Filed:
December 7, 1999
Date of Patent:
December 5, 2000
Assignee:
Boehringer Ingelheim Pharmaceuticals, Inc.
Inventors:
Rajashekhar Betageri, Jean-Marie Ferland, Montse Llinas-Brunet, Neil Moss, John R. Proudfoot
Abstract: Compound of formula (I) active against the Hepatitis C virus: ##STR1## wherein B is an acyl derivative; a is 0 or 1; R.sub.6, when present, is carboxy(lower)alkyl; b is 0 or 1; R.sub.5, when present, is C.sub.1-6 alkyl, or carboxy (lower)alkyl; Y is H or C.sub.1-6 alkyl; R.sub.4 is C.sub.1-10 alkyl; R.sub.3 is C.sub.1-10 alkyl; W is --NH--CH(R.sub.2)--C(O)--, wherein R.sub.2 is C.sub.1-6 alkyl; C.sub.6 or C.sub.10 aryl; C.sub.7-16 aralkyl; or carboxy (lower)alkyl; or W is a proline derivative; Q is a group of the formula --Z(R.sub.1)--C(O)--R.sub.13, wherein Z is CH or N; R.sub.1 is C.sub.1-6 alkyl or C.sub.1-6 alkenyl both optionally substituted with thio or halo,; and R.sub.13 is an activated carbonyl substituent, or Q is a phosphonate group of the formula --CH(R.sub.1)--P(O)R.sub.15 R.sub.16 wherein R.sub.15 and R.sub.16 are independently C.sub.6-20 aryloxy; and R.sub.1 is as defined above.
Abstract: Disclosed is a high throughput compatible assay that is useful for the identification of specific antagonists of TRAF-receptor interactions. The modular flexibility of the assay makes it possible to introduce simple modifications in order to measure the interaction of any TNF receptor cytoplasmic domain (or TRAF-binding protein) with any of the six TRAF proteins, TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 and TRAF6.
Type:
Grant
Filed:
October 29, 1998
Date of Patent:
November 7, 2000
Assignee:
Boehringer Ingelheim Pharmaceuticals, Inc.
Inventors:
Marilyn R. Kehry, Steven S. Pullen, James J. Crute
Abstract: A process for the re-racemisation of a (-)-2-phenylmethyl-3,3-dimethyl-piperidin-4-on derivative wherein a (-)-2-phenylmethyl-3,3-dimethyl-piperidin-4-on derivative of the formula 8.sub.BwhereinR.sub.2 denotes hydrogen C.sub.1 -C.sub.6 -alkyl, halogen, C.sub.1 -C.sub.8 -alkoxy, a benzoyl group bound via an oxygen or an alkylcarboxyl group having a straight chained or branched C.sub.1 -C.sub.6 -lower alkyl group--wherein the alkyl group may optionally be substituted by one or more halogen atoms which may be identical or different;is heated to yield a racemic mixture of compounds of the formulae 8.sub.A and 8.sub.
Type:
Grant
Filed:
November 18, 1999
Date of Patent:
October 31, 2000
Assignee:
Boehringer Ingelheim KG
Inventors:
Matthias Grauert, Herbert Merz, Hanfried Baltes
Abstract: Compound of general formula I ##STR1## wherein A denotes a benzo, indolo or thienyl group;B denotes the group --O--, --S-- or --CHR.sup.5 --, wherein R.sup.5 is hydrogen, (C.sub.1 -.sub.6)alkyl, phenyl or benzyl;R.sup.3 denotes 2- or 3-thienyl, (C.sub.4 -.sub.7)cycloalkyl, (C.sub.4 -.sub.6)cycloalkyl(C.sub.1 -.sub.5)alkyl or ##STR2## wherein R is (C.sub.1 -.sub.4)alkyl, hydroxy, --N.sub.3, halogen (F, Cl, Br, I), CF.sub.3 or (C.sub.1 -.sub.4)alkoxy,u is 0, 1, 2 or 3, andm, R.sup.2, R.sup.4, R.sup.7, R.sup.8 and R.sup.9 are as defined in the specification, as well as pharmaceutical preparations containing these compounds and the pharmaceutical use thereof.
Type:
Grant
Filed:
June 10, 1999
Date of Patent:
October 24, 2000
Assignee:
Boehringer Ingelheim GmbH
Inventors:
Otto Roos, Walter Losel, Dietrich Arndts