Patents Assigned to Gist-Brocades
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Patent number: 4128547Abstract: A process for the preparation of 6-(D-.alpha.-amino-p-hydroxyphenylacetamido)-penicillanic acid or amoxicillin by reacting 6-aminopenicillanic acid with at least two equivalents of a silylating agent producing trimethylsilyl groups in an anhydrous, inert, water-insoluble organic solvent and reacting the resulting product at a temperature below -25.degree. C with an at least equimolar amount of a compound of the formula ##STR1## wherein R.sub.1 and R.sub.7 are lower alkoxy, R.sub.2 is lower alkyl and R.sub.3 is selected from the group consisting of lower alkyl and hydrogen previously prepared from the corresponding Dane salt and an acid chloride under anhydrous conditions in the presence of a tertiary amine in an inert, water-insoluble organic solvent.Type: GrantFiled: November 25, 1977Date of Patent: December 5, 1978Assignee: Gist-Brocades N.V.Inventors: Johannes K. van der Drift, Peter W. Henniger, Gerard J. VAN Veen
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Patent number: 4075337Abstract: R-sulfoxides of the formulae ##STR1## wherein ##STR2## represents an usual penicillin or cephalosporin amide group and X is selected from the group consisting of hydrogen, hydroxy, an alkanoyloxy and the residue of a nucleophilic agent and their salts and esters are prepared by oxidation of the corresponding penicillins and cephalosporins to convert the sulfur atom in the ring to a sulfoxide group and separating and isolating the penicillin- or cephalosporin R-sulfoxide so formed from the reaction mixture or by acylation of the free amino group of the intermediate 6-aminopenicillanic acid R-sulfoxide and 7-aminocephalosporanic acid R-sulfoxide and derivatives. A preferred straight oxidation method is the photosensitized oxygenation method.Type: GrantFiled: November 18, 1975Date of Patent: February 21, 1978Assignee: Gist-Brocades N.V.Inventors: Arthur Friedrich Marx, Jan Verwey, Peter Max Smid
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Patent number: 4075233Abstract: Therapeutically useful 16-dehydro-androstane derivatives of the general formula: ##STR1## processes for their preparation and pharmaceutical compositions for the treatment of dermatological disorders, which contain as active ingredient at least one of the 16-dehydro-androstane derivatives as defined by the above formula.Type: GrantFiled: July 15, 1976Date of Patent: February 21, 1978Assignee: Gist-Brocades N.V.Inventors: Arthur Friedrich Marx, Nicolaas Cornelis Maria Emanuel Barendse
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Patent number: 4067986Abstract: Penicillanic acid derivatives of the formula ##STR1## wherein E is selected from the group consisting of hydrogen, a salt forming cation, and an ester forming residue which is known to improve the absorption characteristics of penicillanic compounds after oral administration to humans or animals, and Y is a group of the formula ##STR2## wherein Z.sub.1 and Z.sub.2 are individually selected from the group consisting of lower alkoxy, optionally substituted phenoxy, optionally substituted benzyl and benzyloxy group, optionally substituted lower alkyl, optionally substituted phenyl, hydroxy and -OM wherein M represents a salt forming cation, and hydrates of the said salts having antibacterial properties and their preparation and novel intermediates.Type: GrantFiled: October 20, 1975Date of Patent: January 10, 1978Assignee: Gist-Brocades N.V.Inventors: Cornelis Adrianus Bruynes, Johannes Karel Van der Drift
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Patent number: 4062948Abstract: A new antibiotic (now called dihydromocimycin) being a yellow, salt-forming weak acid and its non-toxic, pharmaceutically acceptable salts produced by a novel microorganism called Streptomyces ramocissimus, a sample of which is deposited in the collection of "Centraal Bureau voor Schimmel-cultures" at Baarn, The Netherlands, under No. CBS 190.69, or mutants thereof, which antibiotic has antibacterial properties and has been found to be effective against Treponema dysentry, one of the most common swine diseases. Dihydromocimycin may also be converted into mocimycin which is an antibiotic which also possesses growth-promoting properties when added to animal feeds by a dehydrogenation reaction using selenium dioxide as the dehydrogenating agent. The dehydrogenation reaction may be carried out in the presence of a suitable organic solvent.Type: GrantFiled: September 11, 1975Date of Patent: December 13, 1977Assignee: Gist-Brocades N.V.Inventors: Cornelis Vos, Jacobus DEN Admirant, Jan Lambert VAN Os, Hendrik Marten Jongsma, Hermanus Jacobus Kooreman
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Patent number: 4054595Abstract: Novel 18 -, 19 - and 20 -hydroxy-prostaglandin derivatives of the formula I ##STR1## wherein the dotted line in the position 8-12 indicates the optional presence of a double bond, the waved lines in position 15 indicate that the hydroxyl group and the group R.sub.4 are either in .alpha.- or .beta.-position and Z represents a -- CH.sub.2 CH.sub.2 -- or a cis -- CH=CH -- group, and wherein R represents one of the groups: ##STR2## (wherein the waved lines indicate that the hydroxyl groups are either in .alpha.- or .beta.-position and R.sub.1 represents a hydrogen atom, a methyl or ethyl group), R.sub.2 represents either an oxygen atom or a hydrogen atom and an .alpha.- or .beta.-hydroxyl group, R.sub.3 represents a hydrogen atom or a hydroxyl group and R.sub.4 represents a hydrogen atom or a methyl group, with the proviso that when simultaneously, R.sub.1, R.sub.3 and R.sub.4 each represents a hydrogen atom, R.sub.Type: GrantFiled: March 25, 1975Date of Patent: October 18, 1977Assignee: Gist-Brocades N.V.Inventors: Arthur Friedrich Marx, Jean Doodewaard
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Patent number: 4049825Abstract: Diphenylmethoxyethylamines of the general formula ##STR1## in which R.sub.1 represents a fluorine, bromine or chlorine atom, R.sub.2 represents a hydrogen or fluorine atom and R.sub.3 represents a hydrogen, fluorine or chlorine atom, with the provisos that R.sub.3 is a hydrogen atom when R.sub.2 is a fluorine atom, R.sub.1 is a fluorine atom when R.sub.3 is a chlorine atom and R.sub.1 is a fluorine or bromine atom when R.sub.2 and R.sub.3 both are hydrogen atoms, and their non-toxic acid addition salts are disclosed. The compounds have dopaminergic properties and their use is indicated for treating the Parkinson syndrome. Compositions for such use are disclosed.Type: GrantFiled: October 20, 1976Date of Patent: September 20, 1977Assignee: Gist-Brocades N.V.Inventor: Johan Gootjes
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Patent number: 4046761Abstract: Novel azetidine derivatives of the formula ##STR1## wherein R.sub.1 is an acylamido group, R.sub.2 is selected from the group consisting of ##STR2## wherein R.sub.4, R.sub.5 and R.sub.6 are individually selected from the group consisting of hydrogen, lower alkyl and lower alkenyl, n is 2 or 3 and -- in the case when formula IIB is a phenyl -- this group may carry 1 to 4 substituents selected from the group consisting of halogen, lower alkyl, lower alkenyl and phenyl, and R.sub.3 is lower alkyl optionally substituted with 1 or 2 phenyls which phenyl groups may be substituted with nitro and a process for their preparation and process for the preparation of cephalosporanic acid derivatives using the azetidines of formula I as intermediates.This is a division of Serial No. 547,948, filed Feb. 7, 1975 now Pat. No. 4,007,202.Type: GrantFiled: March 4, 1976Date of Patent: September 6, 1977Assignee: Gist-Brocades N.V.Inventors: Jan Verweij, Hong Sheng Tan
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Patent number: 4035352Abstract: Novel 6-substituted amino-penicillanic acid anhydrides useful in the process for the preparation of 7-substituted amino-desacetoxycephalosporanic derivatives comprising converting a 6-substituted amino-penicillanic acid sulfoxide into an anhydride of a 6-substituted amino-penicillanic acid sulfoxide, heating the said acid anhydride intermediate at a temperature up to at most 160.degree. C in a dry inert organic solvent with an anhydrous acid which is capable of causing ring expansion of the penam ring to a .DELTA..sup.3 -cephem ring, in the presence of a silicon-containing compound capable of (a) removing water formed during the ring enlargement of the penam structure fast enough to prevent water hydrolysis of the acid anhydride moiety present and (b) forming neutral or basic products on hydrolysis, the aforesaid acid being strong enough not to be, or not to a substantial extent to be, silylated under the reaction conditions employed, and hydrolyzing the resulting compound in situ to form the .DELTA..sup.Type: GrantFiled: May 6, 1975Date of Patent: July 12, 1977Assignee: Gist-Brocades N.V.Inventors: Jan Verweij, Hong Sheng Tan, Hermanus Jacobus Kooreman
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Patent number: 4024129Abstract: A process for the preparation of acylamido derivatives by reaction of a compound of the formula Z - N = C = O, wherein Z is an optionally substituted alkyl-, aryl- (preferably phenyl or naphthyl) or cycloalkyl or optionally substituted heterocyclic, preferably a penicillanic acid or a cephalosporanic acid nucleus, having carboxyl groups and an optionally present hydroxy group protected, with a carboxylic acid of the formula ##STR1## wherein Z.sup.1 is an optionally substituted hydrocarbon group, in the presence of a catalyst selected from the group consisting of substituted pyridines and their N-oxides, optionally substituted imidazoles or their N-oxides, optionally substituted benzimidazoles or their N-oxides, and optionally substituted imidazo [1,2-.alpha.] pyridines or their N-oxides.Type: GrantFiled: November 3, 1971Date of Patent: May 17, 1977Assignee: Gist-Brocades N.V.Inventors: Peter Wolfgang Henniger, Antoon Van Harrewijn
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Patent number: 4007202Abstract: Novel azetidine derivatives of the formula ##STR1## wherein R.sub.1 is an acylamido group, R.sub.2 is selected from the group consisting of ##STR2## wherein R.sub.4, R.sub.5 and R.sub.6 are individually selected from the group consisting of hydrogen, lower alkyl and lower alkenyl, n is 2 or 3 and -- in the case when formula IIB is a phenyl - this group may carry one to four substituents selected from the group consisting of halogen, lower alkyl, lower alkenyl and phenyl, and R.sub.3 is lower alkyl optionally substituted with 1 or 2 phenyls which phenyl groups may be substituted with nitro and the dotted lines of formula IIB indicate the optional presence of double bonds and a process for their preparation and process for the preparation of cephalosporanic acid derivatives using the azetidines of formula I as intermediates.Type: GrantFiled: February 7, 1975Date of Patent: February 8, 1977Assignee: Gist-Brocades N.V.Inventors: Jan Verweij, Hong Sheng Tan
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Patent number: 4003894Abstract: Process for the preparation of 7-substituted amino-desacetoxycephalosporanic derivatives comprising converting a 6-substituted amino-penicillanic acid sulfoxide into an anhydride of a 6-substituted amino-penicillanic acid sulfoxide, heating the said acid anhydride intermediate at a temperature up to at most 160.degree. C in a dry inert organic solvent with an anhydrous acid which is capable of causing ring expansion of the penam ring to a .DELTA..sup.3 -cephem ring, in the presence of a silicon-containing compound capable of (a) removing water formed during the ring enlargement of the penam structure fast enough to prevent water hydrolysis of the acid anhydride moiety present and (b) forming neutral or basic products on hydrolysis, the aforesaid acid being strong enough not to be, or not to a substantial extent to be, silylated under the reaction conditions employed, and hydrolyzing the resulting compound in situ to form the .DELTA..sup.Type: GrantFiled: May 5, 1975Date of Patent: January 18, 1977Assignee: Gist-Brocades N.V.Inventors: Jan Verweij, Hong Sheng Tan, Hermanus Jacobus Kooreman
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Patent number: 4003932Abstract: Diphenylmethoxyethylamines of the general formula ##STR1## in which R.sub.1 represents a fluorine, bromine or chlorine atom, R.sub.2 represents a hydrogen or fluorine atom and R.sub.3 represents a hydrogen, fluorine or chlorine atom, with the provisos that R.sub.3 is a hydrogen atom when R.sub.2 is a fluorine atom, R.sub.1 is a fluorine atom when R.sub.3 is a chlorine atom and R.sub.1 is a fluorine or bromine atom when R.sub.2 and R.sub.3 both are hydrogen atoms, and their non-toxic acid addition salts are disclosed. The compounds have dopaminergic properties and their use is indicated for treating the Parkinson syndrome. Compositions for such use are disclosed.Type: GrantFiled: March 6, 1973Date of Patent: January 18, 1977Assignee: Gist-Brocades N.V.Inventor: Johan Gootjes
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Patent number: 4002572Abstract: A novel enzyme having a high proteolytic activity in alkaline media and being suitable for inclusion in washing compositions and which is produced by a novel Bacillus strain designated "PB 92", or its proteolytic enzyme producing mutants or variants. A culture of the Bacillus is deposited with the Laboratory for Microbiology of the Technical University of Delft, The Netherlands, where it has been given number OR-60.Type: GrantFiled: November 18, 1975Date of Patent: January 11, 1977Assignee: Gist-Brocades N.V.Inventor: Bauke te Nijenhuis
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Patent number: 3998874Abstract: Substituted phenylene di-ethers of the formula; ##STR1## wherein R represents an isopropyl or tertiary butyl group and X represents hydrogen or lower alkyl, and acid addition salts thereof.The compounds are useful anti-arrhythmic agents and also show local anaesthetic activity in mammals. Their methods of preparation are disclosed and also pharmacological preparations containing the same.Type: GrantFiled: February 1, 1974Date of Patent: December 21, 1976Assignee: Gist-Brocades N.V.Inventor: Wijbe Thomas Nauta
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Patent number: 3966738Abstract: New azetidine derivatives of the formula: ##EQU1## wherein R.sub.1 represents a penicillin- or cephalosporin-amido group, R.sub.2 represents one of the groups of the following formulae: ##EQU2## wherein R.sub.4, R.sub.5 and R.sub.6 are the same or different and each represents a hydrogen atom or a lower alkyl or alkenyl group, n represents 2 or 3 and - in case formula IIB represents a phenyl group - this group may carry one to four further substituents selected from the group consisting of halogen atoms and lower alkyl, lower alkenyl and phenyl groups, R.sub.3 represents an amino group of the formula ##EQU3## wherein R.sub.7 represents a hydrogen atom or a lower alkyl group and R.sub.8 represents a lower alkyl group, or R.sub.3 represents a N,N'-disubstituted hydrazino group wherein the substituents are lower alkyl groups, e.g. the N,N'-diisopropylhydrazino group, or R.sub.3 represents the group -OR.sub.9, wherein R.sub.Type: GrantFiled: February 8, 1974Date of Patent: June 29, 1976Assignee: Gist-Brocades N.V.Inventors: Jan Verwey, Hong Sheng Tan
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Patent number: 3962277Abstract: A new azetidine derivative of the formula: ##EQU1## wherein R.sub.1 represents a penicillin- or cephalosporin-amido group, R.sub.2 represents one of the groups of the following formulae: ##EQU2## wherein R.sub.4, R.sub.5 and R.sub.6 are the same or different and each represents a hydrogen atom or a lower alkyl or alkenyl group, n represents 2 or 3 and - in case formula IIB represents a phenyl group - this group may carry one to four further substituents selected from the group consisting of halogen atoms and lower alkyl, lower alkenyl and phenyl groups,R.sub.3 represents an amino group of the formula ##EQU3## wherein R.sub.7 represents a hydrogen atom or a lower alkyl group and R.sub.8 represents a lower alkyl group, orR.sub.3 represents a N,N'-disubstituted hydrazino group wherein the substituents are lower alkyl groups, e.g. the N,N'-diisopropylhydrazino group, orR.sub.3 represents the group --OR.sub.9, wherein R.sub.Type: GrantFiled: October 6, 1975Date of Patent: June 8, 1976Assignee: Gist-Brocades N.V.Inventors: Jan Verwey, Hong Sheng Tan
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Patent number: 3945994Abstract: Novel therapeutically useful and disinfecting penicillanic and cephalosporanic acid derivatives of the formula: ##SPC1##Wherein W represents a penicillanic or cephalosporanic acid residue or derivatives thereof and wherein Y represents a carbonamido group N-substituted by a phosphorous or sulfur containing residue or Y represents a phosphorous or sulfur containing substituent, and pharmaceutical and disinfecting compositions containing them and their use and process for the preparation of the said compounds.Type: GrantFiled: February 5, 1974Date of Patent: March 23, 1976Assignee: Gist-Brocades N.V.Inventors: Cornelis Adrianus Bruynes, Johannes Karel VAN DER Drift
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Patent number: 3941658Abstract: A method for the rapid determination of the presence or absence of residues of antibiotic such as penicillin, in liquids, for example milk, and meat comprising introducing spores of a microorganism which possesses a high sensitivity for the antibiotic to be determined into an agar medium so that the spores are prevented from starting to germ due to lack of nutrients, but stay alive, and being sufficiently heavily inoculated that after addition of nutrients and incubation at or near optimal temperature in a short time sufficient growth has proceeded so that growth is either observable visually or its indicated by an indicator added to the agar medium, the said spore culture being allowed to solidify in upright test vessels having a cross-sectional dimension sufficiently small to require as little of the agar medium as possible but sufficiently large to enable a correct determination of inhibition of growth of the microorganism to be made, and having a height so that the vessel can contain a sufficient amount oType: GrantFiled: May 22, 1974Date of Patent: March 2, 1976Assignee: Gist-Brocades N.V.Inventors: Sophia Adriana Lameris, Jan Lambert VAN Os, Joannes Gerard Oostendorp
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Patent number: 3930402Abstract: Viscosimeter comprising a flow system for the liquid to be tested, having a narrow zone, zones for determining the pressure of the liquid to be tested located before and after the narrow zone, said zones for determining the pressure of the liquid to be tested being surrounded by tubes of a thin-walled material adapted to transfer the pressure of the liquid within the tubes to pressure transduction liquids outside each of the tubes, each of said pressure transduction liquids being in contact with one of two pressure chambers of a pressure difference recording means in such a manner that the pressures of the liquid to be tested at both sides of the narrow zone are transferred to said pressure chambers.Type: GrantFiled: February 27, 1974Date of Patent: January 6, 1976Assignee: Gist-Brocades N.V.Inventors: Dirk Adrianus Detmar, Jan Van der Sluis, Izak Johannes Stolk, Marius Hendrik Johan Zuidweg