Patents by Assignee Duphar International Research B.V.

Patent number: 6365743
Abstract: The invention relates to a method for the preparation of an enantiomerically pure imidazolyl compound of the general formula wherein: n is 0 or 1; m is 1 or 2; R1 is hydrogen, methyl or ethyl; and C* denotes a chiral center; as well as its pharmaceutically acceptable acid addition salt. The invention further relates to a method of racemization and to a new acid addition salt of this formula I compound and D-pyroglutamic acid and to the hydrochloride monohydrate of the compound of formula I.
Type: Grant
Filed: August 16, 2000
Issued: April 2, 2002
Assignee: Duphar International Research B.V.
Inventors: Paulus F.C. van der Meij, Jan-Maarten Verbeek
Patent number: 6350750
Abstract: The present invention relates to novel compounds, to a method for the preparation of these novel compounds, to pharmaceutical compositions containing one or more of these compounds as an active component and to methods of using these in the treatment of stress-related disorders.
Type: Grant
Filed: September 13, 1999
Issued: February 26, 2002
Assignee: Duphar International Research B.V.
Inventors: Jacobus A. J. Den Hartog, Gerben M. Visser, Johannes W. C. M. Jansen, Eric Ronken, Martinus T. M. Tulp, Jan H. Reinders, Gerrit P. Toorop
Patent number: 6335326
Abstract: The present invention relates to a group of novel benzisoxazole derivatives which are potent and selective antagonists of the dopamine D4-receptor.
Type: Grant
Filed: October 23, 2000
Issued: January 1, 2002
Assignee: Duphar International Research B.V.
Inventors: Jacobus A. J. Den Hartog, Gerben M. Visser, Bartholomeus J. Van Steen, Martinus T. M. Tulp, Eric Ronken, Cornelis G. Kruse, Josephus H. M. Lange
Patent number: 6281216
Abstract: The present invention relates to a group of novel 2-aminoquinoline derivatives which are potent and selective agonists of the dopamine D4-receptor.
Type: Grant
Filed: October 23, 2000
Issued: August 28, 2001
Assignee: Duphar International Research B.V.
Inventors: Jacobus A. J. Den Hartog, Gerben M. Visser, Bartholomeus J. Van Steen, Martinus T. M. Tulp, Eric Ronken, Cornelis G. Kruse
Patent number: 6225312
Abstract: The invention relates to a group of new piperazine and piperidine compounds having interesting pharmacological properties. It has been found that compounds of formula (a) wherein A represents a heterocyclic group of 5-7 ring atoms wherein 1-3 heteroatoms from the group O, N and S are present; R1 is hydrogen or fluoro; R2 is C1-4-alkyl, C1-4-alkoxy or an oxo group, and p is 0, 1 or 2; Z represents carbon or nitrogen, and the dotted line is a single bond when Z is nitrogen, and a single or double bond when Z is carbon; R3 and R4 independently are hydrogen or C1-4-alkyl; n has the value 1 or 2; R5 is halogen, hydroxy, C1-4-alkoxy or C1-4-alkyl, and q is 0, 1, 2 or 3; Y is phenyl, furanyl or thienyl, which groups may be substituted with 1-3 substituents of the group hydroxy, halogen, C1-4-alkoxy, C1-4-alkyl, cyano, aminocarbonyl, mono- or di-C1-4-alkylaminocarbonyl; and salts thereof show high affinity for both the dopamine D2 and serotonin 5-HT1A receptors.
Type: Grant
Filed: March 4, 1999
Issued: May 1, 2001
Assignee: Duphar International Research B.V.
Inventors: Roelof Willem Feenstra, Cornelis Gerrit Kruse, Martinus Theodorus Maria Tulp, Wilma Kuipers, Stephen Kenneth Long
Patent number: 6214829
Abstract: Novel piperazine and piperidine derivative compounds having interesting and advantageous pharmacological properties. The disdosed compounds have the general formula (a) and salts thereof. These compounds have high affinity for both the dopamine D2 receptors and serotonine 5-HT1A receptors, rendering them useful for the treatment of CNS-disorders, in particular schizophrenia.
Type: Grant
Filed: August 31, 1998
Issued: April 10, 2001
Assignee: Duphar International Research B.V.
Inventors: Roelof W. Feenstra, Gerben M. Visser, Cornelis G. Kruse, Martinus T. M. Tulp, Stephen K. Long
Patent number: 6183780
Abstract: The invention relates to an Oral Delayed Immediate Release formulation comprising a compressed core containing one or more active substances surrounded with a coating, wherein release of active substance from the core is caused by rupture of the coating after a definite lag-time, said core comprising one or more immediate release carriers and having no substantial swelling properties upon exposure to gastrointestinal fluids. The invention further relates to formulations containing an Immediate Release formulation combined with one or more Oral Delayed Immediate Release formulations with different lag-times and to a method of preparing an Oral Delayed Immediate Release formulation.
Type: Grant
Filed: September 19, 1997
Issued: February 6, 2001
Assignee: Duphar International Research B.V.
Inventors: Paulus M. Van Balken, Jules A. C. Elbers, Henderik W. Frijlink, Wienman E. Philips
Patent number: 6090812
Abstract: A group of new piperazine and piperidine compounds having interesting advantageous pharmacological properties and have the formula (a) ##STR1## wherein A represents a heterocyclic group having 5-7 ring atoms wherein 1-3 heteroatoms selected from the group O, N and S are present,R.sub.1 is hydrogen or fluoro,R.sub.2 is C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy or an oxo group, and p is 0, 1 or 2,Z represents carbon or nitrogen, and the dotted line represents a single bond when Z is nitrogen, and represents a single or double bond when Z is carbon,R.sub.3 and R.sub.4 independently are hydrogen or C.sub.1-4 -alkyl,n has the value 1 or 2,R.sub.5 is 2-pyridyl, 3-pyridyl or 4-pyridyl substituted at the meta-position with respect to the methylene bridge with a group Y, and optionally substituted with (R.sub.6)q,Y is a phenyl, furanyl or thienyl group, which groups may be substituted with 1-3 substituents from the group hydroxy, halogen, CF.sub.3, C.sub.1-4 -alkoxy, C.sub.1-4 -alkyl, cyano aminocarbonyl, mono- or di-C.sub.
Type: Grant
Filed: September 22, 1998
Issued: July 18, 2000
Assignee: Duphar International Research B.V.
Inventors: Roelof Willem Feenstra, Jacobus A. J. Den Hartog, Cornelis G. Kruse, Martinus T. M. Tulp, Stephen K. Long
Patent number: 6080878
Abstract: The invention relates to a new method of preparing 16-dehydro vitamin D compounds having formula I ##STR1## wherein: R has the epi-configuration or the normal configuration and represents straight or branched C.sub.1-6 -alkyl, C.sub.2-6 -alkenyl, C.sub.3-6 -cycloalkyl, or an aromatic group optionally substituted with halogen, C.sub.1-3 -alkyl or alkoxy,Z is a saturated or unsaturated straight hydrocarbon group or oxahydrocarbon group containing 3-6 C-atoms which may be substituted with OH, F, alkyl (C.sub.1-3) or cycloalkyl (C.sub.3-5),R.sub.1 is hydrogen or an hydroxy protecting group,R.sub.2 is hydrogen or hydroxy, andA and B represent hydrogen or methyl, or together form the methylene group, to the new compounds having this formula and to new intermediates obtainable according to this process.
Type: Grant
Filed: April 29, 1998
Issued: June 27, 2000
Assignee: Duphar International Research B.V.
Inventors: Maria de los Angeles Rey, Antonio Mourino, Ana Fernandez-Gacio, Yagamare Fall, Sebastianus J. Halkes, Koen M. Halkes, Jan-Paul van de Velde, Jan Zorgdrager
Patent number: 6075015
Abstract: Vitamin D.sub.3 analogues of the formula (I): ##STR1## wherein R.sub.1 is hydrogen or hydroxy, R.sub.2 is (C.sub.1 -C.sub.3)alkyl, hydroxy(C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.2)alkoxymethyl, (C.sub.2 -C.sub.3)alkenyl, or (C.sub.2 -C.sub.3)alkynyl, R.sub.3 is a branched or unbranched, saturated or unsaturated aliphatic 3- to 5- membered hydrocarbon or oxahydrocarbon biradical, having at least 3 atoms in the main chain and being optionally substituted with one or more substituents selected from epoxy, fluoro and hydroxy, R.sub.4 is sec. or tert. (C.sub.3 -C.sub.6)alkyl or (C.sub.3 -C.sub.6)cycloalkyl, A and B are each individually hydrogen or methyl, or A and B together from methylene.
Type: Grant
Filed: May 27, 1997
Issued: June 13, 2000
Assignee: Duphar International Research B.V.
Inventors: Jose P. Sestelo, Antonio Mourino, Jose L. Mascarenas, Sebastianus J. Halkes, Jan Zorgdrager, Gerhardus D. H. Dijkstra, Jan-Paul van de Velde
Patent number: 6072062
Abstract: The invention relates to a new vitamin D compound, substituted in the 18-position with an alkyl group, a hydroxy group, an alkoxy group, an alkenyl group, an alkynyl group, a fluorinated alkyl group or a fluorinated alkenyl group. The invention also relates to a method of preparing said vitamin D compound and to a lactone and a hydrindane intermediate.
Type: Grant
Filed: February 13, 1997
Issued: June 6, 2000
Assignee: Duphar International Research B.V.
Inventors: Maria J. Valles, Jose L. Mascarenas, Antonio Mourino, Sebastianus J. Halkes, Jan Zorgdrager
Patent number: 5948909
Abstract: The invention relates to a method for the stereoselective preparation of a hetero-bicyclic alcohol enantiomer, characterized in that a substantially pure enantiomer of the general formula ##STR1## is prepared from a compound of the general formula ##STR2## wherein the variable are as defined as in claim 1. The method comprises the following successive reaction steps:(i) reaction with a substantially enantiomerically pure compound of the general formula ##STR3## wherein Z, R.sub.3 and R.sub.4 are defined as in claim 1; (ii) subjection of the compound formed to a deprotection/ring-closure reaction;(iii) optionally deprotection of the hydroxy group of the ring-closed product.The invention further relates to enantiomerically pure intermediates, the preparation of these intermediates and the preparation of a starting compound.
Type: Grant
Filed: January 22, 1997
Issued: September 7, 1999
Assignee: Duphar International Research B.V.
Inventors: Nicolaas Buizer, Chris G. Kruse, Klara M. Schenk, Belal Shadid
Patent number: 5948410
Abstract: The present invention is concerned with an Influenza surface antigen vaccine obtainable by production from Influenza Viruses propagated on animal cell culture and having a host cell DNA content equal to or less than 25 pg per dose. The present invention is also concerned with a method for the preparation of surface antigen proteins from Influenza Viruses propagated on an animal cell culture comprising the subsequent steps of:a. treatment of the whole virus containing fluid obtained from the cell culture with a DNA digesting enzyme, andb. adding a cationic detergent,followed by isolation of the surface antigen proteins.
Type: Grant
Filed: April 6, 1998
Issued: September 7, 1999
Assignee: Duphar International Research B.V.
Inventors: Gustaar J. M. Van Scharrenburg, Rudi Brands
Patent number: 5929056
Abstract: The present invention relates to vitamin D compounds of the general formula ##STR1## wherein: R.sub.1 is a hydrogen atom or a hydroxy group;R.sub.2 is a (C.sub.1 -C.sub.3)alkyl group, a hydroxy(C.sub.1 -C.sub.3)alkyl group, a (C.sub.1 -C.sub.2)alkoxymethyl group or a (C.sub.2 -C.sub.3)alkenyl or alkynyl group;n is 1;R.sub.3 is a branched or non-branched, saturated or unsaturated, substituted or unsubstituted aliphatic (C.sub.3 -C.sub.7)hydrocarbon or oxyhydrocarbon biradical;R.sub.4 is a branched or straight (C.sub.1 -C.sub.6) alkyl group or a (C.sub.3 -C.sub.6)cycloalkyl group; andA and B are each individually hydrogen atoms or methyl groups, orA and B form together a methylene group.The present compounds find use in cosmetic application and in human and veterinary pharmacotherapeutic practice in the treatment of skin and bone diseases, diseases related to cell differentiation/cell proliferation, imbalance in the immune system and inflammatory diseases.
Type: Grant
Filed: December 11, 1995
Issued: July 27, 1999
Assignee: Duphar International Research B.V.
Inventors: Antonio Mourino, Jose Antonio Martinez, Maria de los Angeles Rey, Juan Granja, Sebastianus J. Halkes
Patent number: 5914263
Abstract: The invention relates to an enzymatic process for the stereoselective preparation of a hetero-bicyclic alcohol enantiomer, characterized in that a substantially pure enantiomer of the general formula ##STR1## wherein X is O, S, NH, N--(C.sub.1 -C.sub.4)alkyl or CH.sub.2 ; Y.sub.1, Y.sub.2 and Y.sub.3 are each independently hydrogen or substituents selected from halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 haloalkyl, nitro and cyano;the NO.sub.2 substituent is attached to the bicyclic ring system in the 5- or 7-position; andthe C*-atom has either the R or the S configuration;is prepared from its corresponding alcohol racemate by the following successive reaction steps:(1) stereoselective esterification,(2) separation of the alcohol from the ester produced,(3) hydrolysis of the ester to produce the corresponding alcohol enantiomer, and(4) conversion of the alcohol enantiomer into the starting racemate under basic conditions in order to allow its reuse.
Type: Grant
Filed: July 23, 1997
Issued: June 22, 1999
Assignee: Duphar International Research B.V.
Inventors: Nicolaas Buizer, Chris G. Kruse, Melle Van Der Laan, Georges Langrand, Gustaaf J.M. Van Scharrenburg, Maria C. Snoek
Patent number: 5817648
Abstract: Vitamin D.sub.3 analogues of the formula (I): ##STR1## wherein R.sub.1 is hydrogen or hydroxy, R.sub.2 is hydrogen, (C.sub.1 -C.sub.3) alkyl, phenyl, or trifluoromethyl, R.sub.3 is branched or unbranched (C.sub.1 -C.sub.4) alkyl, cyclopropyl or CF.sub.3, A and B are individually hydrogen or methyl, or A and B together form methylene, X is CH.sub.2 or O, and n is 2 or 3. These compounds are useful for treating various skin and bone disorders and cancers. These compounds are also useful in cosmetic applications and for diagnostic purposes. Compounds of formula (I) are prepared by reacting a C--25 ester compound with an organometallic compound or by coupling a CD ring ester moiety with a Wittig reagent or an enyne compound to form the desired diene or triene system.
Type: Grant
Filed: May 8, 1996
Issued: October 6, 1998
Assignee: Duphar International Research B.V.
Inventors: Andrzej Kutner, Wanda Wojciechowska, Sebastianus Halkes, Jan-Paul van de Velde
Patent number: 5756104
Abstract: The present invention relates to a vaccine formulation for intranasal or inhalation administration, and to the preparation thereof, which formulation contains antigenic material freely mixed with empty liposomes.
Type: Grant
Filed: June 5, 1995
Issued: May 26, 1998
Assignee: Duphar International Research B.V.
Inventors: Aalzen de Haan, Harmen J. Geerligs, Jan C. Wilschut
Patent number: 5725749
Abstract: The invention relates to a process for the separation of lactulose from a mixture of lactulose and lactose in the presence of a weak acid capable of reversibly forming a complex with lactulose, by using an electrodialysis equipment including an anode and a cathode compartment separated by a plurality of parallel compartments comprising alternating diluate and concentrate compartments, wherein adjacent compartments are separated from each other by permselective membranes; which process is characterized by:(a) continuously passing an alkaline aqueous solution of lactulose, lactose and said complex forming weak acid through the diluate compartments, each diluate compartment being bound by a bipolar membrane at its lateral side facing the cathode and at its opposite lateral side by an anion exchange membrane, separating said compartment from its adjacent concentrate compartment;(b) continuously passing a carrier fluid through the concentrate compartments, each concentrate compartment being bound at its lateral si
Type: Grant
Filed: October 29, 1996
Issued: March 10, 1998
Assignee: Duphar International Research B.V.
Inventor: Hendrik Pluim
Patent number: RE41425
Abstract: A group of new piperazine and piperidine compounds having interesting advantageous pharmacological properties and have the formula (a) wherein A represents a heterocyclic group having 5-7 ring atoms wherein 1-3 heteroatoms selected from the group O, N and S are present, R1 is hydrogen or fluoro, R2 is C1-4-alkyl, C1-4-alkoxy or an oxo group, and p is 0, 1 or 2, Z represents carbon or nitrogen, and the dotted line represents a single bond when Z is nitrogen, and represents a single or double bond when Z is carbon, R3 and R4 independently are hydrogen or C1-4-alkyl, n has the value 1 or 2, R5 is 2-pyridyl, 3-pyridyl or 4-pyridyl substituted at the meta-position with respect to the methylene bridge with a group Y, and optionally substituted with (R6)q, Y is a phenyl, furanyl or thienyl group, which groups may be substituted with 1-3 substituents from the group hydroxy, halogen, CF3, C1-4-alkoxy, C1-4-alkyl, cyano aminocarbonyl, mono- or di-C1-4-alkylaminocarbonyl, R6 is halogen, hydroxy, C1-4-alkoxy or C1
Type: Grant
Filed: April 18, 2008
Issued: July 6, 2010
Assignee: Duphar International Research B.V.
Inventors: Roelof Willem Feenstra, Jacobus A. J. Den Hartog, Cornelis G. Kruse, Martinus T. M. Tulp, Stephen K. Long
Patent number: RE36854
Abstract: The invention relates to a new vitamin D compound of the general formula ##STR1## wherein: R.sub.1 is a hydrogen atom or a hydroxy group;R.sub.2 is a (C.sub.1 -C.sub.3)alkyl group, a hydroxy(C.sub.1 -C.sub.3)alkyl group, a (C.sub.1 -C.sub.2)alkoxymethyl group or a (C.sub.2 -C.sub.3)alkenyl or alkynyl group;R.sub.3 is a branched or non-branched, saturated or unsaturated aliphatic 3- to 5 -membered hydrocarbon or oxahydrocarbon biradical, having at least 3 atoms in the main chain and being optionally substituted with one or more substituents selected from epoxy, fluoro and hydroxy;R.sub.4 is a sec. or tert. (C.sub.3 -C.sub.6)alkyl group or a (C.sub.3 -C.sub.6)cycloalkyl group; andA and B are each individually hydrogen atoms or methyl groups, orA and B form together a methylene group.The invention further relates to a method of preparing these compounds and to their use in pharmacotherapy and cosmetics.
Type: Grant
Filed: September 15, 1997
Issued: September 5, 2000
Assignee: Duphar International Research B.V.
Inventors: Jose P. Sestelo, Antonio Mourino, Jose L. Mascarenas, Sebastianus J. Halkes, Jan Zorgdrager, Gerhardus D. H. Dijkstra, Jan-Paul van de Velde
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