Abstract: The invention relates to the use of betulinic acid and its derivatives for the inhibition and/or prevention or cancer growth. The invention also relates to novel betulinic acid derivatives useful for the inhibition of tumor/cancer cells and a process for the preparation of the derivatives. The invention also relates to the antileukemic, and anti-lymphoma activity of the betulinic acid derivatives, and the use of the derivatives for the treatment of prostate, ovarian and lung cancer.
Type:
Grant
Filed:
February 17, 1999
Date of Patent:
April 10, 2001
Assignee:
Dabur Research Foundation
Inventors:
Sunder Ramadoss, Manu Jaggi, Mohammad Jamshed Ahmed Siddiqui, Achla B. Khanna
Abstract: The invention is directed to compounds, compositions and method of preparation of compounds of formulae I and II:
wherein X, Q1, Q2, R1 and R2 are as defined by the specification. The compounds are disclosed as useful cholesterol-lowering and anti-atherosclerosis agents.
Abstract: Steroid esters of formula I ##STR1## are described, wherein m, n and x are as defined by the specification. The compounds are distinguished from the basic hydroxy compounds by considerably improved solubility as well by increased biological activity and selectivity.The compounds are suitable for the production of pharmaceutical agents.
Type:
Grant
Filed:
December 8, 1997
Date of Patent:
August 1, 2000
Assignee:
Schering AG
Inventors:
Ulrich Klar, Arwed Cleve, Wolfgang Schwede, Gunter Neef, Eckhard Ottow, Kristof Chwalisz, Martin Schneider
Abstract: This invention is relating to new estra-1,3,5(10)-trien-sulfamates carrying at the 3-position an R--SO.sub.2 --O--group, with R being an R.sup.1 R.sup.2 N--group in which R.sup.1 and R.sup.2, independently of each other, represent a hydrogen atom, an alkyl residue with 1-5 C atoms or, together with the N atom, a polymethylene-imino residue with 4-6 C atoms or a morpholino residue.The compounds, according to this invention, are suitable for hormonal contraception and climacteric hormone replacement therapy (HRT) as well as for treatment of gynecological and andrological diseases. Hence, only low hepatic estrogenicity is exhibited by the compounds according to this invention.Also described are processes for preparation of the compounds according to this invention and for preparation of pharmaceutical compositions.
Type:
Grant
Filed:
February 2, 1998
Date of Patent:
June 27, 2000
Assignee:
Jenapharm GmbH & Co. KG
Inventors:
Sigfrid Schwarz, Walter Elger, Hans-Joachim Siemann, deceased, by Margit Lucas, heir, by Frank Siemann, heir, Gudrun Reddersen, Birgitt Schneider
Abstract: Asiatic acid derivatives having a modified A-ring, as represented by formula 1 are disclosed. ##STR1## Pharmaceutical compositions and methods of treating cancer and hepatotoxicity utilizing compounds of formula 1 are also disclosed.
Type:
Grant
Filed:
May 25, 1999
Date of Patent:
June 6, 2000
Assignee:
Dong Kook Pharmaceutical Co., Ltd.
Inventors:
Sang Sup Jew, Hyeung Geun Park, Hee Doo Kim, Young Hoon Jung, Young Choong Kim, Hong Pyo Kim, Mi Kyeong Lee, Hee Sung Choi, Eung Seok Lee, Chi Hyoung Yoo, Doo Yeon Lim, Jeong Hoon Kim, Hee Man Kim, Sung Ki Seo, Tae Gyu Nam, Ducky Han, Pil Jong Shim, Ju Eun Jung, Hee Young Beom
Abstract: The invention relates to use of betulinic acid and/or its derivatives for treating, inhibiting, and/or preventing tumors or cancer growth more particularly, to treating leukemia, lymphomas, lung, prostate and ovarian cancer. This invention also relates to novel betulinic acid derivatives and a composition containing betulinic acid derivatives with or without betulinic acid.
Type:
Grant
Filed:
March 18, 1998
Date of Patent:
April 11, 2000
Assignee:
Dabur Research Foundation
Inventors:
Sunder Ramadoss, Manu Jaggi, Mohammad Jamshed Ahmad Siddiqui
Abstract: This invention describes new, substituted 7.alpha.-(.xi.-aminoalkyl)-estratrienes of general formula I ##STR1## in which side chain SK is a radical of partial formula ##STR2## as well as their physiologically compatible addition salts with organic and inorganic acids.The new compounds represent compounds with very strong antiestrogenic action.The compounds according to the invention are, on the one hand, pure antiestrogens, or, on the other hand, antiestrogens with estrogenic partial action. Based on this spectrum of action, the new compounds are highly suitable for the production of pharmaceutical agents for tumor therapy and hormone replacement treatment.
Type:
Grant
Filed:
January 28, 1999
Date of Patent:
November 16, 1999
Assignee:
Schering AG
Inventors:
Rolf Bohlmann, Dieter Bittler, Josef Heindl, Nikolaus Heinrich, Helmut Hofmeister, Hermann Kunzer, Gerhard Sauer, Christa Hegele-Hartung, Rosemarie Lichtner, Yukishige Nishino, Karsten Parczyk, Martin Schneider
Abstract: The invention describes 14,17-C.sub.2 -bridged steroids of general formula (I), ##STR1## wherein the various R groups are as defined in the specification, and wherein said steroids are in contrast, with the disclaimed compound, the new compounds are available even after peroral administration with high gestagenic action and are suitable for the production of pharmaceutical agents.
Type:
Grant
Filed:
August 18, 1998
Date of Patent:
October 26, 1999
Assignee:
Schering Akitengesellschaft
Inventors:
Klaus Schollkopf, Wolfgang Halfbrodt, Joachim Kuhnke, Wolfgang Schwede, Karl-Heinrich Fritzemeier, Rolf Krattenmacher, Hans-Peter Muhn
Abstract: A process for the production of a compound of formula (II), which comprises reacting an epoxy compound of formula (I) with an alcohol, wherein the reaction is carried out under a basic condition. ##STR1## R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are as defined in the specification. The compounds are useful intermediates for the production of vitamin D.sub.3 derivatives.
Abstract: A process for the isolation of oryzanols from crude dark acid oil (rice bran) which comprises (a) distilling the free fatty acids from crude dark acid oil by conventional methods, (b) hydrolyzing the resultant residue by conventional methods, (c) dissolving the hydrolyzed product in water to form oryzanol containing micellar aggregates and adding dropwise aqueous solution of calcium chloride to form precipitate, (d) extracting the oryzanols from dried precipitate with polar organic solvent and if desired (e) purifying the oryzanols from the organic extract by column chromatography.
Abstract: A Chrysosporium strain No. CBS 123.95, mutants and derivatives thereof, and a method for preparing non-peptide compounds using said strain, are disclosed. Novel compounds of general formula (I), pharmaceutical compositions containing same, and the use of said compounds in anticancer treatments, are also disclosed.
Type:
Grant
Filed:
August 8, 1997
Date of Patent:
December 15, 1998
Assignee:
Rhone-Poulenc Rorer S.A.
Inventors:
Jean Leboul, Didier Van der Pyl, Jean-Jacques Debernard
Abstract: The invention describes 14,17-C.sub.2 -bridged steroids of general formula (I), ##STR1## wherein the various R groups are as defined in the specification, and wherein said steroids are, in contrast with the disclaimed compound 14,17-ethano-19-norpregn-4-ene-3,20-dione bioavailable even after peroral administration with high gestagenic action and are suitable for the production of pharmaceutical agents.
Type:
Grant
Filed:
December 26, 1995
Date of Patent:
October 27, 1998
Assignee:
Schering Aktiengesellschaft
Inventors:
Klaus Schollkopf, Wolfgang Halfbrodt, Joachim Kuhnke, Wolfgang Schwede, Karl-Heinrich Fritzemeier, Rolf Krattenmacher, Hans-Peter Muhn
Abstract: The invention relates to new sulfamate derivatives of 1,3,5(10)-estratriene derivatives of the general formula I ##STR1## wherein the 3-sulfamate moiety is acylated, sulfonated or amidosulfonated. Furthermore, methods for the production of the compound and pharmaceutical preparations containing this compound are described. The compounds according to the invention have an estrogenic effect.
Type:
Grant
Filed:
October 18, 1996
Date of Patent:
January 6, 1998
Assignee:
Jenapharm GmbH & Co. KG.
Inventors:
Sigfrid Schwarz, Walter Elger, Gudrun Reddersen, Birgitt Schneider, Ina Thieme, Margit Richter
Abstract: In this invention, the new etheno- and ethano-19,11-bridged 4-estrenes of general formula I ##STR1## are described, in whichW, R.sup.1, R.sup.2, R.sup.6a, R.sup.6b, R.sup.7, R.sup.14, R.sup.15, R.sup.16, R.sup.11, R.sup.11' and R.sup.19 have the meaning indicated in the description, as well as a process for their production.The new compounds have strong progestational activity and are suitable for the production of pharmaceutical agents.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
December 30, 1997
Assignee:
Schering Aktiengesellschaft
Inventors:
Eckhard Ottow, Wolfgang Schwede, Wolfgang Halfbrodt, Karl-Heinrich Fritzemeier, Rolf Krattenmacher
Abstract: In this invention, the new etheno- and ethano-19,11-bridged 4-estrenes of general formula I ##STR1## are described, in which W, R.sup.1, R.sup.2, R.sup.6a, R.sup.6b, R.sup.7, R.sup.14, R.sup.15, R.sup.16, R.sup.11, R.sup.11' and R.sup.19 have the meaning indicated in the description, as well as a process for their production.The new compounds have strong progestational activity and are suitable for the production of pharmaceutical agents.
Type:
Grant
Filed:
October 13, 1993
Date of Patent:
June 4, 1996
Assignee:
Schering Aktiengesellschaft
Inventors:
Eckhard Ottow, Wolfgang Schwede, Wolfgang Halfbrodt, Karl-Heinrich Fritzemeier, Rolf Krattenmacher
Abstract: 14.alpha.,17.alpha.-(Propano-and 17.sup.2 -propeno)-estratrienes of general formula I ##STR1## in which R.sup.1 means a hydrogen atom, a methyl or an acyl group with 1-12 carbon atoms,R.sup.2 means a hydrogen atom or an acyl group with 1-12 carbon atoms and ##STR2## a C--C single or double bond. The new compounds of general formula I are estrogen effective just as ethinyl estradiol.
Type:
Grant
Filed:
October 29, 1993
Date of Patent:
February 13, 1996
Assignee:
Schering Aktiengesellschaft
Inventors:
James R. Bull, Walter Elger, Karl-Heinrich Fritzemeier, Rolf Krattenmacher
Abstract: 8-En-19,11.beta.-bridged steroids of general formula I ##STR1## that have the 8,9-double bond as a new structural feature, and a process for their production are described. The substituents R.sup.1 R.sup.4 -Y, R.sup.4' -Y.sup.', X and Z have the meaning indicated in the description. The new compounds especially have at their disposal pronounced antigestagen effectivenss and are suitable for the production of pharmaceutical preparations.
Type:
Grant
Filed:
September 28, 1993
Date of Patent:
December 26, 1995
Assignee:
Schering Aktiengesellschaft
Inventors:
Eckhardt Ottow, Gunter Neef, Walter Elger, Martin Schneider, Karl Fritzemeier
Abstract: A process of cyclizing compounds of formula II ##STR1## wherein K, V', R.sup.1 and 1 are as herein defined, is described whereby a compound of formula IVa is produced ##STR2## wherein K, V', R.sup.1, Q, S and 1 are as herein defined. The compounds of formula IVa are useful intermediates in the production of compounds of formula I ##STR3## wherein ring A, B, G, V, Z, R.sup.1 and R.sup.2 are as herein defined.
Type:
Grant
Filed:
August 2, 1993
Date of Patent:
August 29, 1995
Assignee:
Schering Aktiengesellschaft
Inventors:
Eckhard Ottow, Rudolf Wiechert, Gunter Neef, Sybille Beier, Walter Elger, David A. Henderson
Abstract: The new 14.alpha.,16.alpha.-ethano- and 14.alpha.,16.alpha.-etheno-estratrienes of general formula I, ##STR1## are described, in which A-B means a C-C single bond or C-C double bond,R.sub.1 means a hydrogen atom, a methyl or acyl group with 1-12 carbon atoms andX means oxygen or ##STR2## in which R.sub.2 represents a hydrogen atom or an acyl group with 1-12 carbon atoms,and a process for their production. The new compounds are very strong estrogens and are suitable for the production of pharmaceutical agents.
Type:
Grant
Filed:
March 18, 1994
Date of Patent:
August 8, 1995
Assignee:
Schering Aktiengesellschaft
Inventors:
Henry Laurent, Peter Esperling, Walter Elger, Rolf Krattenmacher
Abstract: A process for the production of medrogestone, in which, in an intermediate step, the solvate 3.beta.,5.alpha.,6.beta.-trihydroxy-6.alpha.,17.alpha.-dimethylpregnan-20- one monomethanolate is obtained as a solid, stable compound by displacing the organic solvent from a solution of of 3.beta.,5.alpha.,6.beta.-trihydroxy-6.alpha.,17.alpha.-dimethylpregnan-20- one with a lower alkanol, and a Diels-Alder adduct of 6-methylene-17.alpha.-methylpregn-4-ene-3,20-dione with maleic anhydride is used as an intermediate for production of the corresponding dicarboxylic acid salt for removal of 6-methylene-17.alpha.-methylpregn-4-ene-3,20-dione contamination of the desired product. Another intermediate, 6.beta.-hydroxy-6.alpha.,17.alpha.-dimethylpregn-4-ene-3,20-dione, has been found to prevent smooth muscle proliferation and is useful in the treatment of atherosclerosis and restinosis.
Abstract: 14,16.beta.-Ethano-15.beta.,16.sup.1 -cyclo-14.beta.-estra-1,3,5(10)-trienes of general formula I ##STR1## in which R.sup.1 means a hydrogen atom, a C.sub.1 to C.sub.9 alkyl or C.sub.1 to C.sub.9 acyl radical,R.sup.2 means a hydrogen atom, a C.sub.1 to C.sub.9 alkyl radical, a C.sub.2 to C.sub.9 alkenyl or alkinyl radical andR.sup.3 means a hydroxy group or a C.sub.1 to C.sub.9 acyloxy radical, as well as a process for their production are described. The new compounds have high (peroral) effectiveness and are suitable for the production of pharmaceutical agents.
Type:
Grant
Filed:
November 15, 1993
Date of Patent:
May 23, 1995
Assignee:
Schering Aktiengesellschaft
Inventors:
James R. Bull, Walter Elger, Krzysztof Chwalisz, Karl-Heinrich Fritzemeier
Abstract: The present invention provides a method for producing (+)-estrone derivatives, characterized in that it comprises starting from a certain cyclopentadiene derivative, reacting the derivative with a certain diene compound by an asymmetric Diels-Alder reaction, and via intermediates obtaining a (+)-estron derivative represented by the following formula: ##STR1## wherein R is alkyl of 1-20 carbon atoms. According to the present invention, (+)-estron derivatives can be obtained by limited steps from the starting materials of dicyclopentadiene derivatives.
Abstract: New 11.beta.-phenyl-14.beta.H-steroids of general formula (I), where Z is an oxygen atom or the hydroxyimino-grouping N.about.OH, and M and N are either jointly a second compound or L is a hydrogen atom and M is an .alpha.-permanent hydroxy group and either A and B together are a second compound and D is a hydrogen atom, where R.sup.1 is a five or six-part heteroalkyl residue or a cycloalkyl, cycloalkenyl or aryl residue or A is a hydrogen atom and B and D together are a methylene bridge, where R.sup.1 besides the aforementioned residues may be a possibly substituted hydrocarbon residue with up to 10 C atoms, a possibly substituted amino group, a hydroxy or C.sub.1-8 alkoxy, mercapto or thioalkyl group, R.sup.2 is a methyl or ethyl residue, and R.sup.3 /R.sup.4 represents the usual combination of substituents on the C17 atom in steroid chemistry, having antigestagenic and other properties.
Type:
Grant
Filed:
March 20, 1991
Date of Patent:
September 14, 1993
Assignee:
Schering Aktiengesellschaft
Inventors:
Stefan Scholz, Gunter Neef, Eckhard Ottow, Walter Elger, Sybille Beier, Krzysztof Chwalisz
Abstract: 9.alpha.-Hydroxy-19,11.beta.-bridged steroids of general formula I ##STR1## are described. The more detailed meaning of A, B, R.sup.1, R.sup.2, G, Z, R.sup.4 --Y and R.sup.4' --Y' follows from the description. The steroids of general formula I have antigestagen and/or antiglucocorticoidal action and can be used for the production of pharmaceutical agents.
Type:
Grant
Filed:
January 14, 1992
Date of Patent:
August 3, 1993
Assignee:
Schering Aktiengesellschaft
Inventors:
Eckhard Ottow, Gunter Neef, Rudolf Wiechert, Walter Elger, Sybille Beier, Karl-Heinrich Fritzemeier
Abstract: Novel compounds for the inhibition of sex steroid activity for the treatment of both androgen-related and estrogen-related diseases include for example 15- and 16-halo substituted compounds such as: ##STR1## The compounds are characterized by an estrogenic nucleus substituted with a substituent of the formula --R.sup.1 [B--R.sup.2 --].sub.x L--G whereinat least one of L and G is a polar moiety distanced from a ring carbon of the estrogenic nucleus by a least three intervening atoms:x is an integer from 0-6;R.sup.1 and R.sup.2 are independently either absent or selected from the group consisting of straight- or branched-chain alkylene, straight- or branched-chain alkynylene, straight- or branched-chain alkenylene, phenylene, and fluoro-substituted analogs of the foregoing; andB is either absent or selected from the group consisting of --O--, --Se--, --SO--, --SO.sub.2 --, --NR.sup.3 --, --SiR.sup.3.sub.2, --CR.sup.3 OR.sup.3 --, NR.sup.3 CO--, NR.sup.3 CS--, --CONR.sup.3 --, CSNR.sup.
Abstract: New 9.alpha.-hydroxy-17-methylene steroids are prepared by the introduction of a substituted 17-methylene group in 9.alpha.-hydroxyandrost-4-ene-3, 17-dione.The resulting compounds are useful starting compounds in the synthesis of corticosteroids.
Abstract: The present invention is directed to a group of androstane compounds which contain an ethylene radical bridging the 2- and 19-positions. These compounds are useful as aromatase inhibitors and they are prepared by the cyclization of a 19-[2-(4-toluenesulfonyloxy)ethyl]androst-4-ene-3,17-dione using a strong base.
Type:
Grant
Filed:
November 30, 1990
Date of Patent:
November 24, 1992
Assignee:
Merrell Dow Pharmaceuticals Inc.
Inventors:
J. O'Neal Johnston, Norton P. Peet, Joseph P. Burkhart
Abstract: Disclosed are novel 14,17.alpha.-etheno- and -ethanoestratrienes according to general Formula I ##STR1## wherein X is a --CH.sub.2 --CH.sub.2 or ##STR2## R.sup.1 is a hydrogen atom, a C.sub.1 - to C.sub.15 -acyl, benzoyl, C.sub.1 - to C.sub.15 -alkyl, C.sub.3 - to C.sub.9 -cycloalkyl or alkylcycloalkyl group, andR.sup.2 is the grouping ##STR3## wherein R.sup.3 and R.sup.4 independently of each other mean a hydrogen atom or a straight-chain or branched, optionally partially or completely fluorinated C.sub.1 -C.sub.8 -alkyl group,a process for their preparation, pharmaceutical preparations containing these compounds, as well as their use for the production of medicinal agents.The novel compounds exhibit strong antiestrogenic efficacy.
Type:
Grant
Filed:
July 27, 1990
Date of Patent:
September 8, 1992
Assignee:
Schering Aktiengesellschaft
Inventors:
Rolf Bohlmann, Hermann Kunzer, Rudolf Wiechert, David Henderson, Martin Schneider, Yukishige Nishino
Abstract: New 19,11.beta.-bridged steroids of the general formula I ##STR1## where R.sup.1 stands for a methyl or ethyl radical,R.sup.2 for a hydrogen or chlorine atom or a C.sub.1 -C.sub.4 -alkyl radical,B and G, which are the same or different, respectively for a hydrogen atom, a C.sub.1 -C.sub.4 -alkyl radical or, together, for a second bond between the carbon atoms 6 and 7,B and R.sup.2 together for a methylene or an ethylene group,Z for the radical of a pentagonal or hexagonal ring, which is possibly substituted and possibly unsaturated,V stands for a possibly substituted carbocyclic or heterocyclic aryl radical,the ring A for ##STR2## M and N together meaning a second bond or M a hydrogen atom and N a hydroxy group,X means an oxygen atom, two hydrogen atoms or a hydroxyimino grouping N.about.OH,R.sup.3 and D, which are the same or different, respectively a hydrogen atom, a nitrile radical or a C.sub.1 -C.sub.4 -alkyl radical or, together, a methylene or ethylene group,E a hydrogen atom or a C.sub.1 -C.sub.
Type:
Grant
Filed:
December 9, 1988
Date of Patent:
March 10, 1992
Assignee:
Schering Aktiengesellschaft
Inventors:
Eckhard Ottow, Rudolf Wiechert, Gunter Neef, Sybille Beier, Walter Elger, David A. Henderson
Abstract: Estrane and androstane derivatives of formula I ##STR1## wherein X is bromine, iodine, triphenyltin or trialkyltin of 1 to 6 carbon atoms per alkyl radical,Y represents two hydrogen atoms or methylene,Z represents two hydrogen atoms, oxo or alkylenedioxy of 2 to 6 carbon atoms andV is ethylene, vinylene, 1,3-propylene or cyclopropylene,R.sub.1 is hydrogen or a hydrocarbon radical of up to 8 hydrocarbon atoms, optionally interrupted by an oxa group or substituted by an oxo group,R.sub.2 is methyl or ethyl,R.sub.3 and R.sub.4 represent a carbon-carbon bond or R.sub.3 is hydrogen and R.sub.4 is hydrogen or methyl,.DELTA.symbolizes a 4(5)-double bond if Z signifies two hydrogen atoms or an oxo group; or a 5(6)-double bond or, for the estrane derivatives of formula I, also a 5(10)-double bond, if Z is alkylenedioxy,are pharmacologically effective substances or intermediates for preparation thereof.
Type:
Grant
Filed:
January 19, 1988
Date of Patent:
July 31, 1990
Assignee:
Schering Aktiengesellschaft
Inventors:
Helmut Hofmeister, Henry Laurent, Paul E. Schulze, Klaus Annen, Rudolf Wiechert, Kunhard Pollow, Bernhard Manz, Hans-Joerg Grill