Patents by Inventor Andrzej Kutner
Andrzej Kutner has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 9828323Abstract: Process for preparation of MK-7 type of vitamin K2 is characterized by attaching hexaprenyl chain of “all-trans” configuration to monoprenyl derivative of menadiol following “1+6” synthetic strategy. According to the invention, a-sulfonyl carbanion generated in situ from the protected monoprenyl menadiol of the formula (II), wherein R1 represents C1-3-alkyl group, is reacted with hexaprenyl halide of the formula (VII), wherein X represents halogen atom, preferably bromine, both Z? and Z? represent H or one of Z? and Z? represents H and the other represents phenylsulfonyl group —SO2Ph in the alkylation reaction. The hexaprenyl halide of formula (VII) is obtained by coupling two triprenyl units in alkylation reaction, with or without separation of the intermediates.Type: GrantFiled: October 11, 2013Date of Patent: November 28, 2017Assignee: Nattopharma R & D Ltd.Inventors: Krzysztof Krajewski, Andrzej Kutner, Jadwiga Dzikowska, Regina Gutowska, Marek Napiórkowski, Jerzy Winiarski, Marek Kubiszewski, Łukasz Jedynak, Jacek Morzycki, Stanislaw Witkowski, Aneta Baj, Piotr Wałejko
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Publication number: 20150291498Abstract: Process for preparation of MK-7 type of vitamin K2 is characterized by attaching hexaprenyl chain of “all-trans” configuration to monoprenyl derivative of menadiol following “1+6” synthetic strategy. According to the invention, a-sulfonyl carbanion generated in situ from the protected monoprenyl menadiol of the formula (II), wherein R1 represents C1-3-alkyl group, is reacted with hexaprenyl halide of the formula (VII), wherein X represents halogen atom, preferably bromine, both Z? and Z? represent H or one of Z? and Z? represents H and the other represents phenylsulfonyl group —SO2Ph in the alkylation reaction. The hexaprenyl halide of formula (VII) is obtained by coupling two triprenyl units in alkylation reaction, with or without separation of the intermediates.Type: ApplicationFiled: October 11, 2013Publication date: October 15, 2015Applicant: NATTOPHARMA R&D LTDInventors: Krzysztof KRAJEWSKI, Andrzej KUTNER, Jadwiga DZIKOWSKA, Regina GUTOWSKA, Marek NAPIÓRKOWSKI, Jerzy WINIARSKI, Marek KUBISZEWSKI, Lukasz JEDYNAK, Jacek MORZYCKI, Stanislaw WITKOWSKI, Aneta BAJ, Piotr WALEJKO
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Publication number: 20150031898Abstract: A convergent synthesis of the prostaglandin F2? analogues, travoprost and bimatoprost, was developed employing Julia-Lythgoe olefination of the structurally advanced phenylsulfone with an enantiomerically pure aldehyde ?-chain synthon. The novel convergent strategy allows the synthesis of a whole series of prostaglandin analogues of high purity from a common and structurally advanced prostaglandin intermediate.Type: ApplicationFiled: March 8, 2013Publication date: January 29, 2015Applicant: INSTYTUT FARMACEUTYCZNYInventors: Iwona Dams, Andrzej Kutner, Michal Chodynski, Malgorzata Krupa, Anita Pietraszek, Marta Zezula, Piotr Cmoch, Monika Kosinska
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Publication number: 20130006003Abstract: The present invention discloses the synthone of Formula (I), wherein R1 and R2 are the same or different and represent independently hydrogen atom or hydroxyl protecting group, and its use for preparation of 19-nor vitamin D derivatives of general Formula (IV), wherein represents single or double bond, p represents an integer 0 to 3, R1 and R2 represent independently hydrogen atom or hydroxyl protecting group, R3 represents hydrogen atom, CH3 or hydroxyl group, R4, R5 and R6 represent independently hydrogen atom, C1-C3-alkyl or hydroxyl group or two of R4, R5 and R6 substituents altogether form cyclopropyl group, in particular for preparation of paricalcitol.Type: ApplicationFiled: August 7, 2010Publication date: January 3, 2013Applicant: INSTYTUT FARMACEUTYCZNYInventors: Michal Chodynski, Malgorzata Krupa, Krzysztof Krajewski, Marek Kubiszewski, Andrzej Kutner, Anita Pietraszek, Kinga Trzcinska
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Publication number: 20120101057Abstract: The invention relates to a combined therapy, wherein addition of a vitamin D analogue to the standard treatment regimen based on cytostatics, 5-fluorouracil and/or its precursors, generates potential possibility of achieving beneficial therapeutic effect in the first-line chemotherapy or adjuvant therapy of colorectal carcinoma. Vitamin D analogues are selected from a group consisting of tacalcitol, calcipotriol and 5,6-trans-isomer of calcipotriol.Type: ApplicationFiled: June 9, 2010Publication date: April 26, 2012Applicant: INSTYTUT FARMACEUTYCZNYInventors: Joanna Wietrzyk, Magdalena Milczarek, Andrzej Kutner, Michal Chodynski
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Patent number: 7928063Abstract: Growth hormone-releasing hormone analogs having the amino acid sequence of the formula: Dat-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr10-R11-R12-VAL-Leu-Ala-Gln-Leu-Ser-Ala-R20-R21-Leu-Leu-Gln-Asp-Ile-Nle-Asp-R29-NH2 (I), wherein R11 is hArg, Gab or Gap; R12 is hArg, Orn, Gab or Gap; R20 is hArg, hArg, Gab or Gap; R21 is hArg, Orn, Gab or Gap; R29 is D-Arg, hArg, Gab or Gap; and their pharmaceutically acceptable salts. Said peptides are potent and selective stimulators of GH release and they are highly resistant to enzymatic degradation.Type: GrantFiled: October 30, 2002Date of Patent: April 19, 2011Assignees: Instytut Farmaceutyczny, Zaklady Farmaceutyczne PolpharmaInventors: Jan Izdebski, Danuta Kunce, Alicja Orlowska, Ewa Witkowska, Wieslaw Szelejewski, Andrzej Kutner, Krzysztof Bankowski, Elzbieta Frackiewicz
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Patent number: 7915241Abstract: Disclosed is a process for the preparation of 24-alkyl analogs of cholecalcyferol of Formula 1 having a (5E) or (5Z) configuration, wherein X represents a hydrogen atom, a hydroxy group or an OR1 group, where R1, R2 and R3 may be the same or different and represent groups suitable for hydroxyl protection, and R4 is a C1-6 alkyl chain or a C1-6 cykloalkyl group, optionally substituted with C1-3 alkyl groups, especially for calcipotriol. The invention also provides new intermediates and non-racemic compounds being valuable synthones for the synthesis of pharmacologically active substances.Type: GrantFiled: October 8, 2004Date of Patent: March 29, 2011Assignee: Instytut FarmaceutycznyInventors: Andrzej Kutner, Jacek Martynow, Michal Chodynski, Wieslaw Szelejewski, Hanna Fitek, Malgorzata Krupa
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Patent number: 7897793Abstract: The invention relates to a process for the preparation of 13,14-dihydro-PGF2? derivatives of R or S configuration at carbon 15, represented by the general formula (I), wherein the identity of the substituents is defined in the description. Compounds of the formula (I) are valuable biologically-active substances or intermediates in the preparation thereof. The invention especially relates to the process for preparation of 13,14-dihydro-15(R)-17-substituted-18,19,20-trinor-PGF2?, i.e., latanoprost.Type: GrantFiled: October 18, 2007Date of Patent: March 1, 2011Assignee: Instytut FarmaceutycznyInventors: Jacek Martynow, Julita Szyc, Wieslaw Szelejewski, Osman Achmatowicz, Andrzej Kutner, Krzysztof Wiśniewski, Jerzy Winiarski, Oliwia Zegrocka-Stendel, Piotr Golebiewski
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Patent number: 7829746Abstract: A process for the preparation of calcipotriol at least including: (a) reacting a C-22 phenylsulfonyl derivative of cholecalciferol of Formula 2, wherein R1 and R2 are the same or different and represent hydroxyl protecting groups, with a silyl derivative of alfa-hydroxy aldehyde of Formula 3, wherein R3 represents silyl group of formula Si(R4)(R5)(R6), where R4-R6 are the same or different and represent C1-6 alkyl or phenyl groups, in the presence of a strong organic base in an aprotic solvent, followed by reductive desulfonation of the obtained diastereomeric mixture of alfa-hydroxysulfones with sodium amalgam, removal of the hydroxyl protecting groups, and purification of the product. The process leads to the formation of calcipotriol containing less than 0.3% of the (22Z)-isomer. The obtained calcipotriol is free of mercury traces.Type: GrantFiled: January 11, 2010Date of Patent: November 9, 2010Assignee: Instytut FarmaceutycznyInventors: Andrzej Kutner, Michal Chodynski, Kinga Leszczynska, Wieslaw Szelejewski, Hanna Fitak
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Publication number: 20100222614Abstract: A process for the preparation of calcipotriol at least including: (a) reacting a C-22 phenylsulfonyl derivative of cholecalciferol of Formula 2, wherein R1 and R2 are the same or different and represent hydroxyl protecting groups, with a silyl derivative of alfa-hydroxy aldehyde of Formula 3, wherein R3 represents silyl group of formula Si(R4)(R5)(R6), where R4-R6 are the same or different and represent C1-6 alkyl or phenyl groups, in the presence of a strong organic base in an aprotic solvent, followed by reductive desulfonation of the obtained diastereomeric mixture of alfa-hydroxysulfones with sodium amalgam, removal of the hydroxyl protecting groups, and purification of the product. The process leads to the formation of calcipotriol containing less than 0.3% of the (22Z)-isomer. The obtained calcipotriol is free of mercury traces.Type: ApplicationFiled: January 11, 2010Publication date: September 2, 2010Applicant: INSTYTUT FARMACEUTYCZNYInventors: Andrzej KUTNER, Michal CHODYNSKI, Kinga LESZCZYNSKA, Wieslaw SZELEJEWSKI, Hanna FITAK
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Patent number: 7700580Abstract: A process for the preparation of a pharmaceutical-grade anhydrous calcipotriol comprising: (a) dissolving crude calcipotriol having a water content of X% by weight in a first solvent or in a mixture of two or more first solvents, said first solvent or said mixture of two or more first solvents forming an azeotropic system with water, to obtain a solution of crude calcipotriol; (b) obtaining an intermediate calcipotriol by (i) placing said solution of crude calcipotriol under a reduced pressure and evaporating, if X is greater than or equal to 1, or (ii) crystallizing, if X is lower than 1; and (c) re-dissolving said intermediate calcipotriol in a second solvent or a mixture of two or more second solvents, said second solvent being anhydrous, and crystallizing at least once to obtain pharmaceutical-grade anhydrous calcipotriol.Type: GrantFiled: December 29, 2005Date of Patent: April 20, 2010Assignee: Instytut FarmaceutycznyInventors: Andrzej Kutner, Michal Chodyński, Teresa Ryznar, Hanna Fitak, Jerzy Winiarski, Bartlomiej Górecki, Agnieszka Burzyńska, Wieslaw Szelejewski
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Publication number: 20090093651Abstract: The invention relates to a process for the preparation of 13,14-dihydro-PGF2? derivatives of R or S configuration at carbon 15, represented by the general formula (I), wherein the identity of the substituents is defined in the description. Compounds of the formula (I) are valuable biologically-active substances or intermediates in the preparation thereof. The invention especially relates to the process for preparation of 13,14-dihydro-15(R)-17-substituted-18,19,20-trinor-PGF2?, i.e., latanoprost.Type: ApplicationFiled: April 18, 2006Publication date: April 9, 2009Applicant: INSTYTUT FARMACEUTYCZNYInventors: Jacek Martynow, Julita Szyc, Wieslaw Szelejewski, Osman Achmatowicz, Andrzej Kutner, Krzysztof Wisniewski, Jerzy Winiarski, Oliwia Zegrocka-Stendel, Piotr Golebiewski
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Publication number: 20080255380Abstract: Preparation of sulfonyl derivatives of cholecalciferol of Formula 1, wherein R1 is a protective group, preferably a t-butyl(dimethyl)silyl, and R2 is a heterocyclic group, such as a 2-thiazolyl, a 2-benzothiazolyl, a 1-phenyl-1H-tetrazo-5-yl, a 2-pyridyl, a 2-pyrimidynyl, a 1-isochinolinyl, a 1-methyl-2-imidazyl, or a 4-alkyl-1,2,4-triazo-3-yl, comprises the conversion of the hydroxyl derivative of cholecalciferol into the corresponding sulfide followed by its oxidation to the respective sulfone characterized by the use of a hydroxyl derivative of cholecalciferol as a starting material, in which the triene system is protected as a Diels-Alder adduct, and in particular as an adduct with sulfur dioxide of the Formula 2a. Novel are also the derivatives of Formula 3a and 4a, isolated in the process provided by the invention.Type: ApplicationFiled: May 13, 2005Publication date: October 16, 2008Applicant: INSTYTUT FARMACEUTYCZNYInventors: Michal Chodynski, Malgorzata Krupa, Hanna Fitak, Jerzy Winiarski, Teresa Ryznar, Bartlomiej Gorecki, Wieslaw Szelejewski, Andrzej Kutner
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Publication number: 20080214876Abstract: A process for the preparation of a pharmaceutical-grade anhydrous calcipotriol comprising: (a) dissolving crude calcipotriol having a water content of X % by weight in a first solvent or in a mixture of two or more first solvents, said first solvent or said mixture of two or more first solvents forming an azeotropic system with water, to obtain a solution of crude calcipotriol; (b) obtaining an intermediate calcipotriol by (i) placing said solution of crude calcipotriol under a reduced pressure and evaporating, if X is greater than or equal to 1, or (ii) crystallizing, if X is lower than 1; and (c) re-dissolving said intermediate calcipotriol in a second solvent or a mixture of two or more second solvents, said second solvent being anhydrous, and crystallizing at least once to obtain pharmaceutical-grade anhydrous calcipotriol.Type: ApplicationFiled: December 29, 2005Publication date: September 4, 2008Applicant: INSTYTUT FARMACEUTYCZNYInventors: Andrzej Kutner, Michal Chodynski, Teresa Ryznar, Hanna Fitak, Jerzy Winiarski, Bartlomiej Gorecki, Agnieszka Burzynska, Wieslaw Szelejewski
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Publication number: 20080207926Abstract: The invention relates to a process for the preparation of 13,14-dihydro-PGF2? derivatives of R or S configuration at carbon 15, represented by the general formula (I), wherein the identity of the substituents is defined in the description. Compounds of the formula (I) are valuable biologically-active substances or intermediates in the preparation thereof. The invention especially relates to the process for preparation of 13,14-dihydro-15(R)-17-substituted-18,19,20-trinor-PGF2?, i.e., latanoprost.Type: ApplicationFiled: October 18, 2007Publication date: August 28, 2008Applicant: INSTYTUT FARMACEUTYCZNYInventors: Jacek MARTYNOW, Julita SZYC, Wieslaw SZELEJEWSKI, Osman ACHMATOWICZ, Andrzej KUTNER, Krzysztof WISNIEWSKI, Jerzy WINIARSKI, Oliwia ZEGROCKA-STENDEL, Piotr GOLEBIEWSKI
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Publication number: 20060172927Abstract: Growth hormone-releasing hormone analogs having the amino acid sequence of the formula: Dat-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr10-R11-R12-VAL-Leu-Ala-Gln-Leu-Ser-Ala-R20-R2-Leu-Leu-Gln-Asp-Ile-Nle-Asp-R29-NH2 (I), wherein R11 is hArg, Gab or Gap; R12 is hArg, Orn, Gab or Gap; R20 is hArg, hArg, Gab or Gap; R21 is hArg, Orn, Gab or Gap; R29 is D-Arg, hArg, Gab or Gap; and their pharmaceutically acceptable salts. Said peptides are potent and selective stimulators of GH release and they are highly resistant to enzymatic degradation.Type: ApplicationFiled: October 30, 2002Publication date: August 3, 2006Inventors: Jan Izdebski, Danuta Kunce, Alicja Orlowska, Ewa Witkowska, Wieslaw Szelejewski, Andrzej Kutner, Krzysztof Bankowski, Elzbieta Frackiewicz
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Publication number: 20060111332Abstract: The present invention is a process for the preparation of 17?-hydroxy-7?-methyl-19-nor-17?-pregn-5(10)-en-20-yn-3-one (17?-ethynyl-17?-hydroxy-7?-methyl-5(10)-estren-3-one, tibolone) of formula 1, which comprises hydrolysis of 17?-ethynyl-17?-hydroxy-7?-methyl-5(10)-estrene 3,3-cyclic ketals of formula 2, where groups R1, R2, R3 and R4 are hydrogen atoms or alkyl groups, or R1 and R3, taken together with the carbon atoms within the dioxolane ring to which they are attached, form an alicyclic ring fused to the dioxolane ring, with R2 and R4 being hydrogen atoms, or R1 and R3 together with the carbon atoms to which they are attached form an aromatic ring fused to the dioxolane ring, where R2 and R4, taken together, form a chemical bond within said aromatic ring.Type: ApplicationFiled: October 1, 2003Publication date: May 25, 2006Applicant: Institut FarmaceutycznyInventors: Jacek Martynow, Andrzej Kutner, Wieslaw Szelejewski, Wanda Wojciechowska, Hanna Fitak
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Publication number: 20050119241Abstract: Disclosed is a process for the preparation of 24-alkyl analogs of cholecalcyferol of Formula 1 having a (5E) or (5Z) configuration, wherein X represents a hydrogen atom, a hydroxy group or an OR1 group, where R1, R2 and R3 may be the same or different and represent groups suitable for hydroxyl protection, and R4 is a C1-6 alkyl chain or a C1-6 cykloalkyl group, optionally substituted with C1-3 alkyl groups, especially for calcipotriol. The invention also provides new intermediates and non-racemic compounds being valuable synthones for the synthesis of pharmacologically active substances.Type: ApplicationFiled: October 8, 2004Publication date: June 2, 2005Applicant: Instytut FarmaceutycznyInventors: Andrzej Kutner, Jacek Martynow, Michal Chodynski, Wieslaw Szelejewski, Hanna Fitak, Malgorzata Krupa
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Patent number: 5817648Abstract: 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: GrantFiled: May 8, 1996Date of Patent: October 6, 1998Assignee: Duphar International Research B.V.Inventors: Andrzej Kutner, Wanda Wojciechowska, Sebastianus Halkes, Jan-Paul van de Velde
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Patent number: 5061699Abstract: This invention provides novel side chain homologs of 1.alpha.,25-dihydroxyvitamin D.sub.3 which exhibit enhanced and highly selective activity in inducing differentiation of malignant cells. It also provides a general method of synthesis applicable to the preparation of a variety of vitamin D side chain analogs, and a method of treatment of neoplastic diseases which takes advantage of the selective differentiation activity of the new vitamin D homologs.Type: GrantFiled: October 10, 1989Date of Patent: October 29, 1991Inventors: Hector F. DeLuca, Heinrich K. Schnoes, Kato L. Perlman, Andrzej Kutner