9,10-seco-cyclopentanohydrophenanthrene Ring System Or 9,10-seco Cyclopentanohydrophenanthrene Ring System Having A Bond Between The 3- And 5-positions (e.g., Vitamin D Compounds, Cholecalciferols, Activated 7-dehydrocholesterols, Dihydrotachysterols, 3,5 Cyclovitamin D Compounds, Etc.) Patents (Class 552/653)
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Patent number: 6492353Abstract: This invention relates to 1,3-dihydroxy-20,20-dialkyl-vitamin D3 analogs of Formula (I): compositions comprising the analogs, methods of preparing the analogs and methods of treatment of osteoporosis, secondary hyperparathyroidism, cancer and autoimmune diseases using such analogs.Type: GrantFiled: September 3, 1998Date of Patent: December 10, 2002Assignees: Syntex LLC, Hoffmann-La Roche Inc.Inventors: Percy Sarwood Manchand, Milan Radoje Uskokovic
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Patent number: 6482812Abstract: A method of modifying or altering the structure of a 1&agr;-hydroxylated vitamin D compound to increase its biological activity by altering the conformational equilibrium of the A-ring to favor a chair conformation that presents the 1&agr;-hydroxyl in the axial orientation. This is accomplished by either locking the A-ring chair conformation in a geometry having an axially orientated 1&agr;-hydroxyl, or by the addition of one or more substituents to the A-ring which interact with other substituents in the molecule or on the A-ring to provide a driving force to the A-ring to adopt a chair conformation which presents the 1&agr;-hydroxyl in the axial orientation.Type: GrantFiled: April 16, 2001Date of Patent: November 19, 2002Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Rafal R. Sicinski
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Patent number: 6462031Abstract: A method of purifying 1&agr;-hydroxyvitamin D2 to obtain 1&agr;-hydroxyvitamin D2 in crystalline form. The method includes the steps of boiling a solvent selected from the group consisting of ethyl formate, ethyl acetate and a 2-propanol-hexane mixture under inert atmosphere, dissolving a product containing 1&agr;-hydroxyvitamin D2 to be purified in the solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of 1&agr;-hydroxyvitamin D2 crystals, and recovering the 1&agr;-hydroxyvitamin D2 crystals. Petroleum ether is also added to the solvent after dissolving the product to be purified in the solvent.Type: GrantFiled: December 15, 2000Date of Patent: October 8, 2002Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Rafal R. Sicinski, Hazel Holden, James Brian Thoden
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Patent number: 6455714Abstract: Biotin, fluorescent and chemiluminescent labeled vitamin D compounds are disclosed as well as their use in assays for the presence of vitamin D, its metabolites and vitamin D analogs in biological fluids.Type: GrantFiled: March 19, 2001Date of Patent: September 24, 2002Assignee: A & D BioScience, Inc.Inventors: Michael F. Holick, Rahul Ray
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Publication number: 20020132799Abstract: Compounds expressed by the following general formula (1), 1Type: ApplicationFiled: January 4, 2002Publication date: September 19, 2002Applicant: TEIJIN LIMITEDInventors: Kazuya Takenouchi, Qingzhi Gao, Kenji Manabe, Ryo Sogawa, Yasuhiro Takano, Seiichi Ishizuka
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Patent number: 6452028Abstract: A compound of the formula wherein R is hydrogen or hydroxy, each R1 is ethyl, propyl, butyl, isopropyl or t-butyl, X is ═CH2, or when R is hydroxy, X is hydrogen or ═CH2, and A is —C≡C—, or —CH2—CH2—. These compounds are useful for the treatment of hyperproliferative disorders, skin diseases, and sebaceous gland diseases.Type: GrantFiled: August 25, 2000Date of Patent: September 17, 2002Assignee: Hoffmann-La Roche Inc.Inventors: Andrew David Batcho, Bernard Michael Hennessy, Jerome Anthony Iacobelli, Milan Radoje Uskokovic
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Patent number: 6448421Abstract: The present invention provides crystals of the compound represented by formula (I): crystals of a vitamin D derivative which are obtained by purifying a crude or preliminarily purified product of the vitamin D derivative through a reverse phase chromatography and then crystallizing the purified derivative from an organic solvent; novel compounds which are formed during the synthesis of a vitamin D derivative as by-product; and a method for purifying a vitamin D derivative or the precursor thereof. The method of the present invention makes it possible to supply a highly purified vitamin D derivative, especially ED-71, in bulk and steadily.Type: GrantFiled: December 9, 1998Date of Patent: September 10, 2002Assignee: Chugai Seiyaku Kabushiki KaishaInventor: Tsuyoshi Yamauchi
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Publication number: 20020123638Abstract: This invention provides a novel class of vitamin D related compounds, namely, the 2-alkyl-19-nor-vitamin D derivatives, as well as a general method for their chemical synthesis.Type: ApplicationFiled: October 31, 2001Publication date: September 5, 2002Applicant: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Rafal R. Sicinski
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Patent number: 6440953Abstract: This invention discloses 1&agr;-hydroxy-2-methylene-19-nor-homopregnacalciferol and pharmaceutical uses therefor. This compound exhibits pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anticancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also has little, if any, calcemic activity and therefore may be used to treat immune disorders in humans as well as renal osteodystrophy.Type: GrantFiled: June 11, 2001Date of Patent: August 27, 2002Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Rafal R. Sicinski, Sumithra Gowlugari, Lori A. Plum, Margaret Clagett-Dame
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Patent number: 6441207Abstract: The present invention provides a method for preparing a novel class of vitamin D compounds in which the C-25 or equivalent position has a double bond. In addition, the side chain is optionally extended by one or two methylene or methyne groups. The compounds prepared by the method of the present invention are of value as prodrugs for active 1&agr;, 24-dihydroxylated vitamin D compounds.Type: GrantFiled: November 20, 2000Date of Patent: August 27, 2002Assignee: Bone Care International, Inc.Inventors: Hans Wynberg, Ton Vries, Kees Pouwer
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Publication number: 20020111503Abstract: The present invention provides crystals of the compound represented by formula (I): 1Type: ApplicationFiled: December 9, 1998Publication date: August 15, 2002Inventor: TSUYOSHI YAMAUCHI
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Patent number: 6432936Abstract: A method of purifying 1&agr;-hydroxyvitamin D2 to obtain 1&agr;-hydroxyvitamin D2 in crystalline form. The method includes the steps of boiling a solvent selected from the group consisting of ethyl formate, ethyl acetate and a 2-propanol-hexane mixture under inert atmosphere, dissolving a product containing 1&agr;-hydroxyvitamin D2 to be purified in the. solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of 1&agr;-hydroxyvitamin D2 crystals, and recovering the 1&agr;-hydroxyvitamin D2 crystals. Optionally, petroleum ether may be added to the solvent after dissolving the product to be purified in the solvent.Type: GrantFiled: January 20, 1999Date of Patent: August 13, 2002Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Rafal R. Sicinski, Hazel Holden, James Brian Thoden
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Publication number: 20020107411Abstract: Biotin, fluorescent and chemiluminescent labeled vitamin D compounds are disclosed as well as their use in assays for the presence of vitamin D, its metabolites and vitamin D analogs in biological fluids.Type: ApplicationFiled: March 19, 2001Publication date: August 8, 2002Inventors: Michael F. Holick, Rahul Ray
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Publication number: 20020103172Abstract: A compound of formula (I) in which formula Q is a C1-C6 hydrocarbylene diradical; Y is either a single bond, a carbonyl group or a methylene, ethylene, —CH(OH)—, —O—(C 6 H 4)— (ortho, meta, para) or —S—(C 6 H 4)—(ortho, meta, para) diradical; R 1 and R 2, which may be the same or different, stand for hydrogen or a C 1 -C 6 hydrocarbyl radical; or R 1 and R 2 , when taken together with the carbon atom (starred in formula 1) bearing the group Z, can form a C 3 -C 6 carbocyclic ring; and Z is hydrogen or hydroxy; with the proviso that when, at the same time, Q is ethylene Y is methylene, R 1 and R 2 stand for methyl or trifluoromethyl, and Z is hydroxy, or when, at the same time, Q is ethylene, Y stands for carbonyl or —CH(OH)—, R 1 and R 2 are methyl, and Z is hydroxy, then the configuration at C-20 cannot be E.Type: ApplicationFiled: June 4, 1999Publication date: August 1, 2002Inventor: WELF VON DAEHNE
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Publication number: 20020103173Abstract: Compounds expressed by the following general formula (1), 1Type: ApplicationFiled: January 4, 2002Publication date: August 1, 2002Applicant: TEIJIN LIMITEDInventors: Kazuya Takenouchi, Qingzhi Gao, Kenji Manabe, Ryo Sogawa, Yasuhiro Takano, Seiichi Ishizuka
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Publication number: 20020099039Abstract: Compounds expressed by the following general formula (1), 1Type: ApplicationFiled: January 4, 2002Publication date: July 25, 2002Applicant: TEIJIN LIMITEDInventors: Kazuya Takenouchi, Qingzhi Gao, Kenji Manabe, Ryo Sogawa, Yasuhiro Takano, Seiichi Ishizuka
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Publication number: 20020094972Abstract: A process for preparing vitamin D derivatives having the following formula: 1Type: ApplicationFiled: March 19, 2002Publication date: July 18, 2002Applicant: CHUGAI SEIYAKU KABUSHIKI KAISHAInventors: Susumi Hatakeyama, Hiroyoshi Watanabe, Akira Kawase
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Publication number: 20020091109Abstract: Compounds expressed by the following general formula (1), 1Type: ApplicationFiled: January 4, 2002Publication date: July 11, 2002Applicant: TEIJIN LIMITEDInventors: Kazuya Takenouchi, Qingzhi Gao, Kenji Manabe, Ryo Sogawa, Yasuhiro Takano, Seiichi Ishizuka
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Publication number: 20020087015Abstract: This invention provides a novel class of vitamin D related compounds, namely, the 2-alkylidene-19-nor-vitamin D derivatives, as well as a general method for their chemical synthesis.Type: ApplicationFiled: October 31, 2001Publication date: July 4, 2002Applicant: Wisconsin Alumni Research Foundation of MadisonInventors: Hector F. DeLuca, Rafal R. Sicinski
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Patent number: 6410523Abstract: The present invention provides a vitamin D derivative of the general formula (I): wherein A denotes a straight chain or branched chain alkylene group with 2 to 10 carbon atoms and R denotes SO3R1 in which R1 represents a hydrogen atom or a straight chain or branched chain alkyl group with 1 to 3 carbon atoms or COOR2 in which R2 represents a hydrogen atom or a straight chain or branched chain alkyl group with 1 to 3 carbon atoms; an intermediate compound for synthesis of the vitamin D derivative; and a pharmaceutical composition containing the vitamin D derivative as an active ingredient. The compound of the invention has affinity for a vitamin D receptor and a vitamin D binding protein, and is useful as a drug, such as a drug for treatment of diseases due to abnormal of calcium metabolism. The compound is considered to be a metabolite of a vitamin D derivative having a substituent at the 2&bgr;-position, especially, 2&bgr;-(3-hydroxypropoxy)-1&agr;,25-dihydroxyvitamin D3.Type: GrantFiled: October 6, 2000Date of Patent: June 25, 2002Assignee: Chugai Seiyaku Kabushiki KaishaInventor: Hiroyoshi Watanabe
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Publication number: 20020068723Abstract: A method of modifying or altering the structure of a 1&agr;-hydroxylated vitamin D compound to increase its biological activity by altering the conformational equilibrium of the A-ring to favor a chair conformation that presents the 1&agr;-hydroxyl in the axial orientation. This is accomplished by either locking the A-ring chair conformation in a geometry having an axially orientated 1&agr;-hydroxyl, or by the addition of one or more substituents to the A-ring which interact with other substituents in the molecule or on the A-ring to provide a driving force to the A-ring to adopt a chair conformation which presents the 1&agr;-hydroxyl in the axial orientation.Type: ApplicationFiled: October 31, 2001Publication date: June 6, 2002Applicant: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Rafal R. Sicinski
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Patent number: 6399767Abstract: A process for preparing a compound having structure (I) wherein n is an integer from 1-5; each of R1 and R2 independently is optionally substituted C1-C6 alkyl; each of W and X is independently hydrogen or C1-C6 alkyl; Y is O, S or NR3 where R3 is hydrogen, C1-C6 alkyl or a protective group; and Z is a CD ring structure, a steroid structure, or a vitamin D structure, each of which optionally having structure (IV) wherein W, X, Y and Z are defined above, in the presence of a base, with a compound having structure (V) or (v′) wherein n, R1 and R2 are as defined above, and E is an eliminating group.Type: GrantFiled: May 22, 2000Date of Patent: June 4, 2002Assignees: The Trustees of Columbia University in the City of New York, Chugai Seiyaku Kabushiki KaishaInventors: David A. Horne, Noboru Kubodera, Hiroshi Suzuki, Hitoshi Shimizu
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Patent number: 6399797Abstract: The present invention relates to compounds of formula (I), in which formula X is hydrogen or hydroxy or protected hydroxy; R1 an R2 stand for hydrogen, methyl or ethyl, or, when taken together with the carbon atom bearing the group X, R1 and R2 can form a C3-C5 carbocyclic ring; Q is a C3-C6 hydrocarbylene, hydrocarbylene indicating the diradical obtained after removal of 2 hydrogen atoms for a straight or banched, saturated or unsaturated hydrocarbon, in which one of any CH2 groups may optionally be replaced by an oxygen atom or a carbonyl group, such that the carbon atom (C-22) directly bonded to C-20 is an sp2 or sp3 hybridized carbon atom, i.e. bonded to 2 or 3 other atoms; and in which another of the CH2 groups may be replaced by phenylene, and where Q may optionally be substituted with one or more hydroxy or C1-C4-alkoxy groups.Type: GrantFiled: April 5, 2000Date of Patent: June 4, 2002Assignee: Leo Pharmaceutical Products Ltd. A/S (Løvens kemiske Fabrik Produktionsaktiesel skab)Inventors: Welf von Daehne, Gunnar Grue-Sørensen, Martin John Calverley, Claus Aage Svensgaard Bretting
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Patent number: 6392071Abstract: This invention provides a novel class of vitamin D related compounds, namely, the 2-alkylidene-19-nor-vitamin D derivatives, as well as a general method for their chemical synthesis. The compounds have the formula: where Y1 and Y2, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, R6 and R8, which may be the same or different, are each selected from hydrogen, alkyl, hydroxyalkyl and fluoroalkyl, or when taken together represent the group —(CH2)x— where x is an integer from 2 to 5, and where the group R represents any of the typical side chains known for vitamin D type compounds. These 2-substituted compounds are characterized by relatively high intestinal calcium transport activity and relatively high bone calcium mobilization activity resulting in novel therapeutic agents for the treatment of diseases where bone formation is desired, particularly low bone turnover osteoporosis.Type: GrantFiled: March 31, 2000Date of Patent: May 21, 2002Assignee: Wisconsin Alumni: Research FoundationInventors: Hector F. DeLuca, Rafal R. Sicinski
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Patent number: 6387673Abstract: In accordance with the present invention, it has been discovered that histone deacetylase associates with hormone receptor complexes and contributes to the repression thereof. It has further been discovered that exposure of a repressed system to histone deacetylase inhibitors relieves this repression. Thus, histone deacetylase inhibitors have been found to be useful for the activation of genes responsive to hormone receptors. In accordance with another aspect of the invention, formulations useful for modulation of hormone-mediated processes have been developed. In addition, assays have been developed for the identification of compounds useful to modulate the above-described processes.Type: GrantFiled: May 1, 1997Date of Patent: May 14, 2002Assignee: The Salk Institute for Biological StudiesInventors: Ronald M. Evans, Laszlo Nagy
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Patent number: 6380408Abstract: Novel sulfur-containing analogs of 1&agr;,25-dihydroxy vitamin D3 are provided. These analogs are synthesized in a convergent manner by joining A-ring and C,D ring fragments. Each analog with 1&agr;,3&bgr;-substituent stereochemistry shows a pharmacologically desirable combination of high antiproliferative and high transcriptional activities in vitro and also low calcemic activity in vivo.Type: GrantFiled: March 31, 2000Date of Patent: April 30, 2002Assignee: The Johns Hopkins UniversityInventors: Gary H. Posner, Jae-Kyoo Lee, Qiang Wang, Kenneth R. Crawford, Gyoonhee Han
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Publication number: 20020049344Abstract: The invention concerns new vitamin D derivatives of general formula (I) a process for their production, their use for production of medicaments, and intermediate products used in the process.Type: ApplicationFiled: December 11, 1998Publication date: April 25, 2002Inventors: ANDREAS STEINMEYER, GERALD KIRSCH, GUNTER NEFF, KATICA SCHWARZ, RUTH THIEROFF-EKERDT, HERBERT WIESINGER, MARTIN HABEREY, MARIANNE FAHNRICH
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Patent number: 6376480Abstract: A method of preparing a pharmaceutical composition, comprising combining a pharmaceutically compatible vehicle with a compound according to formula (I)Type: GrantFiled: December 18, 2000Date of Patent: April 23, 2002Assignee: Schering AktiengesellschaftInventors: Gerald Kirsch, Andreas Steinmeyer, Günter Neef, Katica Schwarz, Ruth Thieroff-Ekerdt, Herbert Wiesinger, Andreas Menrad, Martin Haberey
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Publication number: 20020045606Abstract: Analogs of vitamin D3, in particular esters of vitamin D3 and uses thereof, are described. The compounds of the present invention can be used as substitutes for natural and synthetic vitamin D3 compounds.Type: ApplicationFiled: December 1, 2000Publication date: April 18, 2002Inventors: Satyanarayana G. Reddy, Gino John Sasso
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Patent number: 6372731Abstract: A vitamin D derivative and its uses with substituents at C-25 of general formula IType: GrantFiled: March 31, 1998Date of Patent: April 16, 2002Assignee: Schering AktiengesellschaftInventors: Gerald Kirsch, Andreas Steinmeyer, Günter Neef, Katica Schwarz, Ruth Thieroff-Ekerdt, Herbert Wiesinger, Andreas Menrad, Martin Haberey
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Patent number: 6372926Abstract: 1-Hydroxy pregnacalciferol derivatives of formula (I) and their corresponding 5,6-trans isomers wherein R1 is hydroxyl or lower alkoxy and R2 is optionally hydroxylated or lower alkoxylated lower alkynyl or R1 is C(RA) (RB)CH3 where RA is optionally hydroxylated or lower alkoxylated lower alkynyl and RB is hydroxyl or lower alkoxy or RA and RB together represent oxo and R2 is hydrogen, hydroxyl or lower alkoxy, and R3 and R4 represent hydrogen atoms, exhibit anti-progesterone activity and may be useful as antineoplastic, antifertility, antiproliferative, immunosuppressive and/or antiinflammatory agents.Type: GrantFiled: February 19, 1999Date of Patent: April 16, 2002Assignee: Research Institute for Medicine and ChemistryInventors: Robert Henry Hesse, Maurice Murdoch Pechet, Sundara Katugam Srinivasasetty Setty
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Patent number: 6362350Abstract: A method of purifying 1&agr;,24(S)-dihydroxyvitamin D2 to obtain 1&agr;,24(S)-dihydroxyvitamin D2 in crystalline form. The method includes the steps of boiling a solvent under inert atmosphere, dissolving a product containing 1&agr;,24(S)-dihydroxyvitamin D2 to be purified in the solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of 1&agr;,24(S)-dihydroxyvitamin D2 crystals, and recovering the 1&agr;,24(S)-dihydroxyvitamin D2 crystals. The purification technique involves using one of several binary solvent systems, namely, acetone and hexane, 2-propanol and hexane, or ethyl formate and petroleum ether.Type: GrantFiled: November 10, 1999Date of Patent: March 26, 2002Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Rafal R. Sicinski, Hazel Holden, James Brian Thoden
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Patent number: 6358939Abstract: Methods of treating inflammatory bowel disease are described, and in particular the prevention and treatment of inflammatory bowel disease in humans as well as other animals. These methods involve the administration of biologically active vitamin D compounds, and therapeutic compositions thereof, so that the symptoms of Inflammatory Bowel Disease are reduced or relieved.Type: GrantFiled: December 21, 1999Date of Patent: March 19, 2002Assignee: Northern Lights Pharmaceuticals, LLCInventors: Colleen E. Hayes, Faye E. Nashold
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Patent number: 6359012Abstract: The invention provides a method for making 24(S)-hydroxyvitamin D2 which is a stereospecific synthesis.Type: GrantFiled: December 22, 1999Date of Patent: March 19, 2002Assignee: Bone Care International, Inc.Inventors: Harold Meckler, Mark A. Helle, William B. Geiss, Brian T. Gregg
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Patent number: 6359152Abstract: This invention provides a novel class of vitamin D compounds, namely, 13-ethyl and 13-vinyl-18,19-dinor-vitamin D derivatives, as well as a general method for their chemical synthesis. The compounds have the formula: where Y1 and Y2, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, R6 is selected from the group consisting of an ethyl or vinyl radical, and where the group R represents any of the typical side chains known for vitamin D type compounds. These 18-substituted compounds are characterized by minimal intestinal calcium transport activity and minimal bone calcium mobilization activity resulting in novel therapeutic agents for the treatment of secondary hyperparathyroidism.Type: GrantFiled: May 15, 2001Date of Patent: March 19, 2002Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Zu Y. Cai
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Publication number: 20020032340Abstract: A compound having the formula (4):Type: ApplicationFiled: October 3, 2001Publication date: March 14, 2002Applicant: CHUGAI SEIYAKU KABUSHIKI KAISHAInventor: Akira Kawase
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Patent number: 6344437Abstract: The present invention is to provide a novel medicine, drink, food or feed having an action of strengthening bone. More specifically, the present invention is to provide a medicine, drink, food or feed combined with collagen, fraction containing collagen or degradation product thereof. Fraction containing collagen was prepared by mincing skin corium layer into pieces, defatting it and lyophylization or by pulverizing bone, decalcifying it and lyophylization. Oral administration of these can stimulate proliferation of osteoblast, inhibit bone resorption and strengthen bone. They can be useful for improvement of osteoporosis, bone fracture, bone pain, etc.Type: GrantFiled: March 17, 1997Date of Patent: February 5, 2002Assignee: Snow Brand Milk Products Co., Ltd.Inventors: Yukihiro Takada, Seiichiro Aoe, Ken Kato, Yasuhiro Toba, Junichi Yamamura
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Publication number: 20020012710Abstract: A mixture of a pomegranate seed oil product and a pomegranate juice product and a pharmaceutical composition containing same. The mixture, which is a cancer chemopreventive, includes a pomegranate seed oil product and pomegranate juice product. The pharmaceutical composition includes physiologically active amounts of pomegranate seed oil product, a pomegranate juice product and a pharmaceutically acceptable carrier. According to some disclosed embodiments, a pomegranate peel product is further included. Further disclosed is a selective estrogen receptor modulator and other biologically active compounds derived from pomegranates as well as methods of use thereof.Type: ApplicationFiled: May 18, 2001Publication date: January 31, 2002Applicant: RIMONEST LTD.Inventor: Ephraim Philip Lansky
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Publication number: 20020010163Abstract: 1-Hydroxy pregnacalciferol derivatives of formula (I) and their corresponding 5,6-trans isomers wherein R1 is hydroxyl or lower alkoxy and R2 is optionally hydroxylated or lower alkoxylated lower alkynyl or R1 is C(RA) (RB)CH3 where RA is optionally hydroxylated or lower alkoxylated lower alkynyl and RB is hydroxyl or lower alkoxy or RA and RB together represent oxo and R2 is hydrogen, hydroxyl or lower alkoxy, and R3 and R4 represent hydrogen atoms, exhibit anti-progesterone activity and may be useful as antineoplastic, antifertility, antiproliferative, immunosuppressive and/or antiinflammatory agents.Type: ApplicationFiled: February 19, 1999Publication date: January 24, 2002Inventors: ROBERT HENRY HESSE, MAURICE MURDOCH PECHET, SUNDARA KATUGAM S SETTY
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Publication number: 20020006917Abstract: A method of modifying or altering the structure of a 1&agr;-hydroxylated vitamin D compound to increase its biological activity by altering the conformational equilibrium of the A-ring to favor a chair conformation that presents the 1&agr;-hydroxyl in the axial orientation. This is accomplished by either locking the A-ring chair conformation in a geometry having an axially orientated 1&agr;-hydroxyl, or by the addition of one or more substituents to the A-ring which interact with other substituents in the molecule or on the A-ring to provide a driving force to the A-ring to adopt a chair conformation which presents the 1&agr;-hydroxyl in the axial orientation.Type: ApplicationFiled: July 20, 2001Publication date: January 17, 2002Applicant: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Rafal R. Sicinski
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Patent number: 6331642Abstract: Compounds of the formula wherein R1 is hydrogen or an alkyl group; R2 is hydrogen or an alkyl group; or R1, R2 and C20 together are cyclopropyl; R3 is alkyl, hydroxy-alkyl or fluoroalkyl; and R4 is alkyl, hydroxy-alkyl or fluoroalkyl which are useful in the treatment of breast cancer, prostate cancer, myeloid leukemia benign prostate growth, baldness and osteoporosis.Type: GrantFiled: May 24, 2000Date of Patent: December 18, 2001Assignee: Hoffmann-La Roche Inc.Inventors: Andrew David Batcho, Bernard Michael Hennessy, Milan Radoje Uskokovic
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Publication number: 20010051617Abstract: This invention provides a novel class of vitamin D compounds, namely, 13-ethyl and 13-vinyl-18,19-dinor-vitamin D derivatives, as well as a general method for their chemical synthesis.Type: ApplicationFiled: May 15, 2001Publication date: December 13, 2001Applicant: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Zu Y. Cai
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Publication number: 20010051738Abstract: A method of purifying 1&agr;,24(S)-dihydroxyvitamin D2 to obtain 1&agr;,24(S)-dihydroxyvitamin D2 in crystalline form. The method includes the steps of boiling a solvent under inert atmosphere, dissolving a product containing 1&agr;,24(S)-dihydroxyvitamin D2 to be purified in the solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of 1&agr;,24(S)-dihydroxyvitamin D2 crystals, and recovering the 1&agr;,24(S)-dihydroxyvitamin D2 crystals. The purification technique involves using one of several binary solvent systems, namely, acetone and hexane, 2-propanol and hexane, or ethyl formate and petroleum ether.Type: ApplicationFiled: June 22, 2001Publication date: December 13, 2001Applicant: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Rafal R. Sicinski, Hazel Holden, James Brian Thoden
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Patent number: 6329538Abstract: A compound of the formula wherein R is hydrogen or hydroxy, each R2 is independently H or halogen, X is ═CH2, or when R is hydroxy, X is hydrogen or ═CH2, and A is —C≡C—, or —CH2—CH2—, provided that when A is —CH2—CH2—, R2 is H.Type: GrantFiled: August 25, 2000Date of Patent: December 11, 2001Assignee: Hoffmann-La Roche Inc.Inventors: Andrew David Batcho, Bernard Michael Hennessy, Jerome Anthony Iacobelli, Milan Radoje Uskokovic
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Patent number: 6316642Abstract: This invention provides a novel class of vitamin D related compounds, namely, 2-alkyl-19-nor-vitamin D derivatives, as well as a general method for their chemical synthesis. The compounds have the formula: where Y1 and Y2, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, R6 is selected from the group consisting of alkyl, hydroxyalkyl and fluoroalkyl, and where the group R represents any of the typical side chains known for vitamin D type compounds. These 2-substituted compounds, especially the 2&agr;-methyl and the 2&agr;-methyl-20S derivatives, are characterized by relatively high intestinal calcium transport activity and relatively high bone calcium mobilization activity resulting in novel therapeutic agents for the treatment of diseases where bone formation is desired, particularly low bone turnover osteoporosis.Type: GrantFiled: March 31, 2000Date of Patent: November 13, 2001Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Rafal R. Sicinski
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Publication number: 20010039359Abstract: A method of purifying 1&agr;-hydroxyvitamin D2 to obtain 1&agr;-hydroxyvitamin D2 in crystalline form. The method includes the steps of boiling a solvent selected from the group consisting of ethyl formate, ethyl acetate and a 2-propanol-hexane mixture under inert atmosphere, dissolving a product containing 1&agr;-hydroxyvitamin D2 to be purified in the solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of 1&agr;-hydroxyvitamin D2 crystals, and recovering the 1&agr;-hydroxyvitamin D2 crystals. Petroleum ether is also added to the solvent after dissolving the product to be purified in the solvent.Type: ApplicationFiled: December 15, 2000Publication date: November 8, 2001Inventors: Hector F. DeLuca, Rafal R. Sicinski, Hazel Holden, James Brian Thoden
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Patent number: 6310226Abstract: The present invention relates to compounds of formula (I) in which formula X is hydrogen or hydroxy; R1 and R2 which may be the same or different, stand for hydrogen or C1-C5 hydrocarbyl; or R1 and R2, taken together with the carbon atom bearing the group X, can form a C3C8 carbocyclic ring; Q is methylene, ethylene, tri- or tetra-methylene and may optionally be substituted with an oxy group, —OR3, in which R3 is hydrogen, methyl or ethyl; Y is either a single bond or C1-C2 hydrocarbylene; and one or more carbons with in R1, R2, and/or Y may optionally be substituted with one or more fluorine atoms, or with a hydroxyl group. The compounds show anti-inflammatory and immunomodulating effects as well as strong activity in inducing differentiation and inhibiting undesirable proliferation of certain cells.Type: GrantFiled: April 30, 1999Date of Patent: October 30, 2001Assignee: Leo Pharmaceutical Products Ltd.Inventors: Martin John Calverley, Henrik Pedersen
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Patent number: 6307075Abstract: Novel analogs of 1&agr;,25-dihydroxyvitamin D3 which are selective agonists for the genomic responses or agonists or antagonists for the rapid cellular responses in a wide array of diseases in which 1&agr;,25-dihydroxyvitamin D3 or its prodrugs are involved. Novel analogs have general formulae represented by compounds of groups I-V. A method for treatment and prevention of diseases connected with the endocrine system.Type: GrantFiled: November 30, 1999Date of Patent: October 23, 2001Assignee: The Regents of the University of CaliforniaInventors: Anthony W. Norman, William H. Okamura
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Patent number: 6306844Abstract: This invention provides pharmaceutical uses for 2&agr;-methyl-19-nor-20(S)-1&agr;, 25-dihydroxyvitamin D3. This compound is characterized by high bone calcium mobilization activity demonstrating preferential activity on bone. This results in a novel therapeutic agent for the treatment of diseases where bone formation is desired, particularly osteoporosis. This compound also exhibits pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis. This compound also increases both breaking strength and crushing strength of bones evidencing use in conjunction with bone replacement surgery such as hip and knee replacements.Type: GrantFiled: July 14, 2000Date of Patent: October 23, 2001Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Connie M. Smith
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Patent number: 6291693Abstract: Kit comprising biotin, fluorescent and chemiluminescent labeled vitamin D compounds are disclosed. The disclosed kit may be used in assays for the presence of vitamin D, its metabolites and vitamin D analogs in biological fluids.Type: GrantFiled: July 1, 1999Date of Patent: September 18, 2001Assignee: A & D BioScience, Inc.Inventors: Michael F. Holick, Rahul Ray