The Three Cyclos Consist Of Two Carbocyclic Rings And A Five-membered Hetero Ring Which Includes A Ring Nitrogen (e.g., Ergolines, Etc.) Patents (Class 546/67)
  • Patent number: 9193728
    Abstract: This disclosure is directed to fused tetracyclic pyrido[4,3-b]indoles and pyrido[3,4-b]indoles. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.
    Type: Grant
    Filed: February 18, 2011
    Date of Patent: November 24, 2015
    Assignee: Medivation Technologies, Inc.
    Inventors: Sarvajit Chakravarty, Barry Patrick Hart
  • Patent number: 8895743
    Abstract: Provided herein are novel methysergide derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders or symptoms thereof, such as, migraine and Parkinson's disease using the compounds and compositions disclosed herein. In still other embodiments, provided herein, such as, for example, are methods for antagonizing the 5-HT2B receptor without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein such as, for example, are methods of agonizing the 5-HT1A receptor using the compounds and compositions disclosed herein.
    Type: Grant
    Filed: December 19, 2013
    Date of Patent: November 25, 2014
    Assignee: Map Pharmaceuticals, Inc.
    Inventors: Libo Wu, Jian Zhang
  • Publication number: 20140045879
    Abstract: The present invention relates to the use of ergot derivatives or ergolines, and in particular of lisuride and terguride for the prophylaxis and treatment of constrictive capillary arteriopathy. Constrictive capillary arteriopathy refers to the diseases pulmonary arterial hypertension, endogenously induced or exogenously induced glomeruloscleroses as well as secondary Raynaud's syndrome.
    Type: Application
    Filed: January 20, 2012
    Publication date: February 13, 2014
    Inventors: Rudolf Reiter, Johannes Tack, Reinhard Horowski
  • Patent number: 8324386
    Abstract: Disclosed is a series of somatostatin-dopamine chimeric analogs which retain both somatostatin and dopamine activity in vivo. An example is: 6-n-propyl-8?-ergolinglmethylthioacetyl-D-Phe-c(Cys-Tyr-D-Trp-Lys-Abu-Cys)-Thr-NH2.
    Type: Grant
    Filed: October 7, 2009
    Date of Patent: December 4, 2012
    Assignee: IPSEN Pharma S.A.S.
    Inventors: Michael D. Culler, Zheng Xin Dong, Sun H. Kim, Jacques-Pierre Moreau
  • Publication number: 20110124600
    Abstract: Disclosed is the oral use of dopamine partial agonists and the physiologically acceptable salts thereof in order to create a pharmaceutical preparation for treating the restless legs syndrome, which effectively controls the symptoms while having a significantly smaller undesired effect of a medicament than medicaments known in prior art.
    Type: Application
    Filed: June 13, 2003
    Publication date: May 26, 2011
    Inventors: Karel Kranda, Reinhard Horwski, Karel Sonka, Johannes Tack
  • Patent number: 7939665
    Abstract: This invention relates to a new and efficient process for the production of dopamine agonists such as Cabergoline and the intermediates thereof.
    Type: Grant
    Filed: May 4, 2007
    Date of Patent: May 10, 2011
    Assignee: Apotex Pharmachem Inc.
    Inventors: Zhi-Xian Wang, YuanQiang Li, Murali Kondamreddy, Xiongwei Cai
  • Patent number: 7858791
    Abstract: A process for preparing cabergoline (I) from ergoline-8?-carboxylic acid ester (XIII) comprising the following steps. (XIII), (XVI), (XVII), (XVIII), (XIX), (I). The present case also relates to the intermediates (XVI), (XVII), (XVIII) and (XIX) as well as the polymorphic amorphous form of Cabergoline (I) and the production thereof.
    Type: Grant
    Filed: March 2, 2005
    Date of Patent: December 28, 2010
    Assignee: Richter Gedeon Vegyeszeti Gyar RT
    Inventors: Janos Galambos, Laszlo Czibula, Ferenc Sebök, Sandorné Balint, Ferencné Kassai, Gyorgyi Ignaczné Szendrei, Adam Demeter
  • Publication number: 20100179304
    Abstract: Disclosed is a series of somatostatin-dopamine chimeric analogs which retain both somatostatin and dopamine activity in vivo.
    Type: Application
    Filed: October 7, 2009
    Publication date: July 15, 2010
    Inventors: Michael D. Culler, Zheng Xin Dong, Sun H. Kim, Jacques-Pierre Moreau
  • Patent number: 7622476
    Abstract: This invention relates to 1-allyl ergot alkaloids and their derivatives with selective antagonistic properties to 5-HT2 receptors for the prevention of, and relief from, migraine-related headache, Parkinson's disease, disorders of the thrombocyte function, etc.
    Type: Grant
    Filed: December 21, 2002
    Date of Patent: November 24, 2009
    Assignee: Axxonis Pharma AG
    Inventors: Miroslav Flieger, Heinz Pertz, Karel Kranda, Jan Cvak, Sven Jaenichen, Erika Glusa
  • Patent number: 7541463
    Abstract: The invention discloses novel sulfur-containing naphthalimide derivatives, and the preparation and uses thereof. The conjugated plane of naphthalimide derivatives of the invention is enlarged by incorporating 5-or 6-membered heteroaromatic ring and/or introducing S heteroatom, thus increasing the anti-tumor activity of naphthalimide. The compounds of the invention displays significant inhibiting activities to the proliferation of various tumor cells such as human lung cancer, gastric cancer, liver cancer, leucocythemia and the like. The inhibition of cell proliferation is dose-dependent.
    Type: Grant
    Filed: October 31, 2005
    Date of Patent: June 2, 2009
    Assignees: East China University of Science and Technology, Shanghai Institute of Materia Medica, Chinese Academy of Science, Dalian University of Technology
    Inventors: Xuhong Qian, Yonggang Li, Yufang Xu, Jian Ding, Liping Lin, Zehong Miao, Hong Zhu, Baoyuan Qu
  • Patent number: 7531551
    Abstract: Provided are new crystalline Forms VIII, IX, XI, XII, XIV, XV, XVI, XVII, and XVIII of cabergoline. Also provided are novel processes for preparation of cabergoline Form I, Form II, Form VII, and amorphous cabergoline.
    Type: Grant
    Filed: May 7, 2004
    Date of Patent: May 12, 2009
    Assignee: IVAX Pharmaceuticals s.r.o.
    Inventors: Roman Bedná{hacek over (r)}, Ladislav Cvak, Alexandr Jegorov, Roman Sobotik
  • Patent number: 7339060
    Abstract: A method of preparing cabergoline Form I, comprising forming a solvate including cabergoline and a p-disubstituted benzene of formula (A) or 1,3,5-trimethylbenzene and obtaining cabergoline Form I from the solvate. Another aspect of the present invention provides a method for preparing cabergoline Form I comprising dissolving cabergoline in p-disubstituted benzene or 1,3,5-trimethylbenzene and recovering the cabergoline Form I polymorph, suitably by direct crystallization of Form I or by recovery of a solvate which can be converted to Form I. Another aspect of the present invention provides a novel cabergoline polymorph designated cabergoline Form FB and a method of preparing said polymorph by dissolving or forming a solvate of cabergoline in fluorobenzene and recovering cabergoline Form FB.
    Type: Grant
    Filed: November 7, 2005
    Date of Patent: March 4, 2008
    Assignee: Resolution Chemicals, Ltd.
    Inventors: Alan Kenneth Greenwood, Derek McHattie, Parveen Bhatarah, Mahmoud Aloui
  • Patent number: 7238810
    Abstract: A method of preparing cabergoline Form I, comprising forming a solvate including cabergoline and 4-fluorotoluene or 1,3,5-trimethylbenzene and obtaining cabergoline Form I from the solvate. Another aspect of the present invention provides a method for preparing cabergoline Form I comprising dissolving cabergoline in 4-fluorotoluene or 1,3,5-trimethylbenzene and recovering the cabergoline Form 1 polymorph. Cabergoline Form I can then be obtained from the solution, suitably by direct crystallization of Form I or by recovery of a solvate which can be converted to Form I.
    Type: Grant
    Filed: April 7, 2005
    Date of Patent: July 3, 2007
    Inventors: Parveen Bhatarah, Derek McHattie, Alan Greenwood, Paul Christopher Marcus Hedger
  • Patent number: 7186837
    Abstract: The present invention discloses a method for preparing cabergoline form I by combining cabergoline and a solvent comprising ethylbenzene to form a solvate and obtaining form I from the solvate. Also disclosed in a method for preparing cabergoline form I by combining cabergoline and a first solvent to form a solution and additionally including a second solvent to the solution, followed by crystallization to form cabergoline form I. Further disclosed is a solvate form of cabergoline comprising cabergoline and ethylbenzene and, optionally, n-heptane.
    Type: Grant
    Filed: February 18, 2005
    Date of Patent: March 6, 2007
    Assignee: Resolution Chemicals
    Inventors: Alan Greenwood, Derek McHattie, Parveen Bhatarah, Mark Philip Gamble
  • Patent number: 7026483
    Abstract: The invention provides methods for preparing amorphous physical form of cabergoline, and solvate form A of cabergoline useful in the preparation of the first mentioned physical form. A method for treating a prolactin disorder with medicaments prepared from amorphous physical form of cabergoline and solvate form A of cabergoline is also disclosed.
    Type: Grant
    Filed: April 20, 2004
    Date of Patent: April 11, 2006
    Assignee: Finetech Laboratories, Ltd.
    Inventors: Arie Gutman, Boris Tishin, Alex Vilenski, Albay Agazade, Boris Pertzikov, Gennady Nisnevich
  • Patent number: 7019140
    Abstract: A process for the synthesis of pergolide (Formula (I)) (D-6-n-propyl-8?methylmercaptomethylergo line) from acid 9,10-dihydrolysergic is herein disclosed. The process can be carried out without isolating most intermediates and is particularly convenient both from the yield and safety standpoint.
    Type: Grant
    Filed: March 10, 2003
    Date of Patent: March 28, 2006
    Assignee: Antibioticos S.p.A.
    Inventors: Walter Cabri, Paolo Paissoni, Jacopo Roletto, Piera Fonte, Sara Olmo
  • Patent number: 6953854
    Abstract: A process for producing crystalline form I of cabergoline, which process comprises crystallization of the desired form from a toluene/diethyl ether mixture comprising raw cabergoline, followed by recovery and drying of the resulting crystals. A new solvate form V of cabergoline, useful as an intermediate, is also provided.
    Type: Grant
    Filed: October 31, 2003
    Date of Patent: October 11, 2005
    Assignee: Pharmacia
    Inventors: Attilio Tomasi, Stefania Magenes, Mario Ungari, Giuliano Ramella, Gianfranco Pallanza
  • Publication number: 20040209910
    Abstract: The invention provides methods for preparing amorphous physical form of cabergoline, and solvate form A of cabergoline useful in the preparation of the first mentioned physical form. A method for treating a prolactin disorder with medicaments prepared from amorphous physical form of cabergoline and solvate form A of cabergoline is also disclosed.
    Type: Application
    Filed: April 20, 2004
    Publication date: October 21, 2004
    Inventors: Arie Gutman, Boris Tishin, Alex Vilenski, Albay Agazade, Boris Pertzikov, Gennady Nisnevich
  • Publication number: 20040092744
    Abstract: A process for producing crystalline form I of cabergoline, which process comprises crystallization of the desired form from a toluene/diethyl ether mixture comprising raw cabergoline, followed by recovery and drying of the resulting crystals.
    Type: Application
    Filed: October 31, 2003
    Publication date: May 13, 2004
    Applicant: Pharmacia Italia, S.p. A.
    Inventors: Attilio Tomasi, Stefania Magenes, Mario Ungari, Giuliano Ramella, Gianfranco Pallanza
  • Patent number: 6727363
    Abstract: A process for producing crystalline form I of cabergoline, which process comprises crystallization of the desired form from a toluene/diethyl ether mixture comprising raw cabergoline, followed by recovery and drying of the resulting crystals. A new solvate form V of cabergoline, useful as an intermediate, is also provided.
    Type: Grant
    Filed: February 3, 2003
    Date of Patent: April 27, 2004
    Assignee: Pharmacia Italia SPA
    Inventors: Attilio Tomasi, Stefania Magenes, Mario Ungari, Giuliano Ramella, Gianfranco Pallanza
  • Publication number: 20040072855
    Abstract: Crystalline form II of cabergoline, a pharmaceutical composition containing it and a process for its preparation are disclosed. The process may comprise crystallization from s solution of raw cabergoline in an organic solvent at low temperatures or submitting to a slurry procedure a mixture of cabergoline forms I and II in a solvent at a temperature below 30° C.
    Type: Application
    Filed: October 31, 2003
    Publication date: April 15, 2004
    Applicant: Pharmacia Italia, S.p.A.
    Inventors: Attilio Tomasi, Stefania Magenes, Giuliano Ramella, Mario Ungari, Marco Pandolfi
  • Patent number: 6680327
    Abstract: Crystalline form VII of cabergoline, a pharmaceutical composition containing it and a process for its preparation are disclosed. The process may comprise a slurry procedure using form I or mixture of forms I and VII of cabergoline in a solvent at a temperature above 30° C.
    Type: Grant
    Filed: September 18, 2002
    Date of Patent: January 20, 2004
    Assignee: Pharmacia Italia SpA
    Inventors: Ilaria Candiani, Raffaella Budelli, Marco Pandolfi, Mario Ungari
  • Publication number: 20030187013
    Abstract: Crystalline form II of cabergoline, a pharmaceutical composition containing it and a process for its preparation are disclosed. The process may comprise crystallization from a solution of raw cabergoline in an organic solvent at low temperatures or submitting to a slurry procedure a mixture of cabergoline Forms I and II in a solvent at a temperature below about 30° C.
    Type: Application
    Filed: January 16, 2003
    Publication date: October 2, 2003
    Inventors: Attilio Tomasi, Stefania Magenes, Giuliano Ramella, Mario Ungari, Marco Pandolfi
  • Publication number: 20020177709
    Abstract: A process for preparation of N-(ergoline-8&bgr;-carbonyl)ureas of the formula [I] their stereoisomers as well as acid addition salts thereof which process comprises silylating an ergoline-8&bgr;-carboxamide of the formula [2], 1
    Type: Application
    Filed: April 16, 2001
    Publication date: November 28, 2002
    Inventors: Arie L. Gutman, Gennadiy Nisnevich, Igor Rukhman, Boris Tishin, Alex Vilensky, Boris Pertsikov
  • Patent number: 6395901
    Abstract: Process for the preparation of compounds active in the treatment of Parkinson's disease, and such compounds, having general formula (VI) wherein R4 may be, independently, a linear, branched or cyclic, saturated or unsaturated C1-8 alkyl radical, such as, for example, the radicals methyl, ethyl, propyl, butyl, isobutyl, tert-butyl, pentyl, cyclopentyl, hexyl, cyclohexyl and octyl. The process utilizes as starting materials the compound of formula (I) wherein R1 represents a linear, branched or cyclic, saturated or unsaturated C1-8 alkyl residue.
    Type: Grant
    Filed: March 21, 2001
    Date of Patent: May 28, 2002
    Assignee: Poli Industria Chimica S.p A.
    Inventors: Alberto Mangia, Paride Grisenti
  • Patent number: 6388079
    Abstract: This invention relates to a process for preparing pergolide, which comprises the steps of reacting 9,10-dihydrolysergol with an acid anhydride at an elevated temperature in the presence of a catalyst to form a triacylated product intermediate; reducing the triacylated product intermediate with a reducing agent in a solvent to form a primary amino alcohol intermediate; and reacting the amino alcohol intermediate with dimethyl disulfide and trialkyl phosphine, aryl phosphine or the polymeric derivatives of phosphine analogs thereof in a polar solvent to obtain pergolide; or the steps of reacting 9,10-dihydrolysergol with dimethyl disulfide and trialkyl phosphine, aryl phosphine or the polymeric derivatives of phosphine analogs thereof in a polar solvent to form a methylsulfide intermediate; reacting the methylsulfide intermediate with an acid anhydride at an elevated temperature in the presence of a catalyst to form a diacylated amide intermediate; and reducing the diacylated amide intermediate with a reducing
    Type: Grant
    Filed: August 29, 2000
    Date of Patent: May 14, 2002
    Assignee: Scinopharm Singapore Pte Ltd.
    Inventors: Edwin S. C. Wu, Mark Wu
  • Patent number: 6358967
    Abstract: The invention relates to novel derivatives of ergoline of the general formula 1 in which R1 together with the two adjacent N atoms is the residue of a diamine and R4 together with the two adjacent carbonyl groups is the residue of a dicarboxylic acid. R2, R3, R6, R7, R8 can be H or an organic radical. R7 and R8 are H or together are a bond. The compounds show a strong antihypertensive effect. These effects moreover occur after intravenous and enteral administration even at dosages in the region of a few &mgr;g/kg (body weight). The compounds can accordingly be used as pharmaceuticals for hypertensive diseases in human medicine.
    Type: Grant
    Filed: April 19, 2001
    Date of Patent: March 19, 2002
    Assignee: CyBio Screening GmbH
    Inventors: Ralf Wyrwa, Albert Haertl, Erika Glusa, Susanne Grabley, Ralf Thiericke
  • Publication number: 20020002170
    Abstract: The invention provides a compound of formula I 1
    Type: Application
    Filed: July 16, 2001
    Publication date: January 3, 2002
    Inventors: Rainer M. Luond, Markus Banziger, Peter Frey
  • Publication number: 20010044118
    Abstract: The present invention provides hapten derivatives useful for the preparation of antigens, antibodies and reagents for use in immunoassays for the detection of LSD and 2-oxo-3-hydroxy LSD. In the present invention, the 2-oxy LSD nucleus is derivatized out of the indole nitrogen to form an aminoalkyl derivative. The resulting haptens can then be further modified at this functionalized position for linking to appropriate immunogenic or labeling groups to provide reagents for immunoassays having substantially equal specificity for both LSD and 2-oxo-3-hydroxy-LSD.
    Type: Application
    Filed: December 8, 2000
    Publication date: November 22, 2001
    Inventors: Mitali Ghoshal, Stephen Vitone, Gerald F. Sigler, Alan J. McNally
  • Patent number: 6242603
    Abstract: The present invention relates to a novel process for preparing lysergic acid by isomerizing paspalic acid, using a tetraalkylammonium hydroxide.
    Type: Grant
    Filed: June 21, 2000
    Date of Patent: June 5, 2001
    Assignee: Aventis Pharma S.A.
    Inventor: Jean-Claude Gaullier
  • Patent number: 6087371
    Abstract: Ergoline derivative having formula (I) wherein R.sub.1 is hydrogen atom or C.sub.1-4 alkyl group; R.sub.2 is hydrogen, chlorine, or bromine atom, methyl or C.sub.1-4 alkylthio group; n is 0, 1 or 2; the substituent at position 8 is in .alpha. or .beta. configuration; Het represents an aromatic 5-membered heterocyclic ring, said ring having three heteroatoms which are the same or different and which are selected from the group consisting of sulfur, oxygen and nitrogen atom and X is hydrogen, chlorine or bromine or fluorine atom, or a pharmaceutically acceptable acid addition salt thereof are active at the Central Nervous System level. A process for their preparation is also described, as are pharmaceutical compositions containing them.
    Type: Grant
    Filed: August 17, 1998
    Date of Patent: July 11, 2000
    Assignee: Pharmacia & Upjohn S.p.A.
    Inventors: Sergio Mantegani, Tiziano Bandiera, Maurizio Meroni, Mario Varasi, Carla Caccia
  • Patent number: 6060483
    Abstract: The present invention provides the new use in the treatment of neurodegenerative diseases with ergoline derivatives of formula (I) ##STR1## wherein R.sub.1 represents a hydrogen atom or a linear or branched C.sub.1 -C.sub.5 alkyl or C.sub.2 -C.sub.5 alkenyl group optionally substituted with a C.sub.3 -C.sub.7 cycloalkyl, a hydroxy group or a R.sub.3 -substituted phenyl group wherein R.sub.3 is a hydroxy or a hydroxymethyl group; R.sub.2 represents a hydrogen atom or a linear or branched C.sub.1 -C.sub.5 alkyl or a C.sub.2 -C.sub.5 alkenyl group optionally substituted with a hydroxy group, or a R.sub.3 -substituted phenyl group wherein R.sub.3 is as above defined, or with a C.sub.1 -C.sub.5 alkoxy group; the symbols--at positions 2,3 and 8, 9 independently denote a single or double chemical bond and Z represents a group (CH.sub.2).sub.n OH, wherein n is 0 or an integer from 1 to 3, or a group C(R.sub.4).sub.2 OH wherein R.sub.4 is a C.sub.1 -C.sub.
    Type: Grant
    Filed: December 28, 1998
    Date of Patent: May 9, 2000
    Assignee: Pharmacia & Upjohn S.p.A.
    Inventors: Sergio Mantegani, Enzo Brambilla, Nicola Carfagna, Mario Varasi
  • Patent number: 5480885
    Abstract: A method of treating psychosis including administering an antipsychotically effective amount of an ergolinyl derivative of 2-propinylamine of the formula I ##STR1## wherein, R.sub.1, R.sub.2, and R.sub.3 independently represent a hydrogen atom or a straight-chain or branched-chain C.sub.1 -C.sub.6 alkyl group, X represents a hydrogen or a halogen atom, Z represents a carbonyl or methylene group, and C.sub.9 - - - -C.sub.10 represents a single or a double, diastereomeric forms, racemates and acid addition salts thereof.
    Type: Grant
    Filed: December 2, 1993
    Date of Patent: January 2, 1996
    Assignee: Lek, Tovarna Farmacevtskih in Kemicnih
    Inventors: Rudolf Rucman, Breda Bole-Vunduk, Magdalena Ocvirk, Bogomila Lavric, Igor Krisch
  • Patent number: 5430031
    Abstract: The present invention provides compounds of the formula (I) ##STR1## wherein A, R.sub.1, R.sub.2 and R.sub.3 are defined as in the specification, or a pharmaceutically acceptable salt thereof. A process for their preparation and the pharmacetical compositions comprising them are also provided.
    Type: Grant
    Filed: December 20, 1993
    Date of Patent: July 4, 1995
    Assignee: Farmitalia Carlo Erba S.r.l.
    Inventors: Sergio Mantegani, Enzo Brambilla, Carla Caccia, Nicola Carfagna
  • Patent number: 5401748
    Abstract: 2,14-Disubstituted ergolines of formula I ##STR1## in which R, R.sup.2, R.sup.6, R.sup.14 and X have the meaning named in the application, as well as their production and use in pharmaceutical agents, are described.
    Type: Grant
    Filed: March 12, 1993
    Date of Patent: March 28, 1995
    Assignee: Schering Aktiengesellschaft
    Inventors: Gerhard Sauer, Helmut Wachtel, Peter A. Loschmann
  • Patent number: 5288724
    Abstract: There are disclosed novel ergoline derivatives of 2-propinylamine of the general formula I ##STR1## wherein R.sub.1, R.sub.2 and R.sub.3 independently represent a hydrogen atom or a straight-chain or branched-chain C.sub.1 -C.sub.6 alkyl group,X represents a hydrogen or a halogen atom,Z represents a carbonyl or methylene group andC.sub.9 C.sub.10 represents a single or a double bond, diastereomeric forms, racemates and acid addition salts thereof.There are also described a process for the manufacture of the compounds of the general formula I and a pharmaceutical composition containing the same.The compounds of the general formula I can be used in the pharmaceutical industry as active substances for the manufacture of medicaments used in the treatment of hypertension, migraine, anxiety states, depressions, obesity etc.
    Type: Grant
    Filed: June 22, 1992
    Date of Patent: February 22, 1994
    Assignee: LEK, tovarna farmacevtskih
    Inventors: Rudolf Rucman, Breda Bole-Vunduk, Magdalena Ocvirk, Bogomila Lavric, Igor Krisch
  • Patent number: 5219862
    Abstract: Compounds of formula I ##STR1## in which R.sup.2 means optionally substituted C.sub.1-7 alkyl, C.sub.2-7 alkenyl, CH.sub.2 --O--C.sub.1-4 alkyl or CH.sub.2 --S--C.sub.1-4 alkylR.sup.6 means C.sub.2-6 alkyl, C.sub.3-6 alkenyl or C.sub.3-5 -cycloalkyl-C.sub.1-2 alkyl andR.sup.8 means CH.sub.2 --X, ##STR2## in which X stands for CN, OCH.sub.3, SCH.sub.3 or CONH.sub.2 and R.sup.1 stands for hydrogen, halogen, methyl or methoxy, and R.sup.3 and R.sup.4 each mean C.sub.1-4 alkyl or (CH.sub.2).sub.n --N(CH.sub.3).sub.2, in which n=1-4, and their acid addition salts, the process for their production, their use as pharmaceutical agents as well as intermediate compounds are described.
    Type: Grant
    Filed: December 21, 1990
    Date of Patent: June 15, 1993
    Assignee: Schering Aktiengesellschaft
    Inventors: Gerhard Sauer, Thomas Brumby, Helmut Wachtel, Jonathan Turner, Peter A. Loschmann
  • Patent number: 5097031
    Abstract: The invention relates to a novel stereoselective process for the preparation of dihdyrolysergol from lysergol by hydrogenation in the presence of solvent and palladium catalyst applied on a carrier, which comprises hydrogenating lysergol in the presence of one or more aprotic solvent(s) containing tertiary nitrogen atom(s) and a palladium catalyst applied on activated carbon, and recovering the product obtained from the reaction mixture in a known manner.
    Type: Grant
    Filed: June 22, 1990
    Date of Patent: March 17, 1992
    Assignee: Richter Gedeon Vegyeszeti Gyar R.T.
    Inventors: Istvan Polgar, Jozsef Foldesi, Janos Kiss, Piroska Major nee Forstner, Karoly Molnar, Andras Sugar, Tamas Szen, Katalin Balogh nee Nemes
  • Patent number: 5063234
    Abstract: A method of inhibiting bone demineralization comprising administration of an effective amount of a compound having the formula ##STR1## where X is CH or N;Y is O or S;R.sup.1 is 2-propenyl, C.sub.1 -C.sub.3 alkyl, benzyl or substituted benzyl where the substitutents are one or two of the same or different and are selected from methyl, ethyl, methoxy, ethoxy, hydroxy, chloro, bromo, or fluoro;R.sup.2 is C.sub.2 -C.sub.3 alkyl, allyl or cyclopropylmethyl;R.sup.3 and R.sup.4 are both hydrogen or combine to form a carbon-carbon bond; and pharmaceutically acceptable acid addition salts thereof to a mammal requiring bone demineralization inhibition.
    Type: Grant
    Filed: April 11, 1991
    Date of Patent: November 5, 1991
    Assignee: Eli Lilly and Company
    Inventors: Henry U. Bryant, James A. Clemens
  • Patent number: 4980475
    Abstract: Processes for the preparation of esters of N.sub.1 -methyl-10.alpha.-methoxylumilysergol are described, in which lysergol esters are subjected to N-methylation and subsequently to photochemical reaction with methanol/H.sub.2 SO.sub.4. The esters of N.sub.1 -methyl-10-methoxylumilysergol obtained in this way can then be saponified or converted directly into other esters.
    Type: Grant
    Filed: March 26, 1985
    Date of Patent: December 25, 1990
    Assignee: I d B Holding S.P.A.
    Inventors: Ezio Bombardelli, Giuseppe Mustich
  • Patent number: 4968801
    Abstract: Ergoline derivatives of general Formula I ##STR1## wherein C.sub.8 C.sub.9 and C.sub.9 C.sub.10 are both CC-single bonds or one is a C.dbd.C-double bond,R.sup.6 is C.sub.1-4 alkyl,R.sup.8 is methyl, hydroxymethyl, carbonylmethoxy, ureido or N,N-diethylureido, each in the .alpha.- or .beta.-position, andR is hydrogen or nitro,are prepared by dehydrogenation of corresponding 2,3-dihydroergoline derivatives using an electrophilic reagent in an apolar solvent and a base.
    Type: Grant
    Filed: May 25, 1989
    Date of Patent: November 6, 1990
    Assignee: Schering Aktiengesellschaft
    Inventors: Gerhard Sauer, Helmut Biere, Gregor Haffer, Andreas Huth
  • Patent number: 4939258
    Abstract: Cycloalkyl or ketocycloalkyl esters of 1-substituted-6-C.sub.1-4 straight chain alkyl (or allyl)-ergoline-8.beta.-carboxylic acids, useful as 5HT receptor antagonists.
    Type: Grant
    Filed: January 10, 1990
    Date of Patent: July 3, 1990
    Assignee: Eli Lilly and Company
    Inventors: Kathleen R. Whitten, William L. Garbrecht, Gifford P. Marzoni, C. John Parli
  • Patent number: 4908449
    Abstract: A process for preparing 1-methyllysergol or 10.alpha.-methoxy-1-methyllumilysergol, which comprises adding a base, which is an alkali metal hydride or alcoholate, to a solution of lyergol or 10.alpha.-methoxylumilysergol in a polar aprotic solvent in such a way that the molecular ratio between the base and the lysergol or 10.alpha.-methoxylumilysergol remains less than 0.5:1, and then adding a methylating agent which is methyl iodide, methyl sulphate or trimethylsulphonium iodide.1-methyllysergol and 10.alpha.-methoxy-1-methyllysergol are useful intermediates in the synthesis of pharmacological compounds.
    Type: Grant
    Filed: March 27, 1989
    Date of Patent: March 13, 1990
    Assignee: Rhone-Poulenc Sante
    Inventor: Christian Gervais
  • Patent number: 4874768
    Abstract: The disclosure relates to 1,2-substituted ergoline derivatives of general Formula I ##STR1## wherein X is an oxygen or sulfur atom,R.sup.1 is a lower alkyl group,R.sup.2 is halogen, acyl, a saturated or unsaturated lower alkyl group which can optionally be substituted by OR.sup.4 wherein R.sup.4 is hydrogen, lower alkyl, tetrahydropyranyl or cycloalkyl, or by an optionally substituted aryl residue, an S-R.sup.5 -group wherein R.sup.5 means a lower alkyl group which can optionally be substituted by aryl or an optionally substituted aryl residue, a ##STR2## wherein n=2 o4 3, or a --CHO-group, R.sup.3 is lower alkyl or acyl, andC.sub.9 -C.sub.10 is a CC-single or a CC-double bond, and the hydrogen atom in the 10-position is in the .alpha.-location if C.sub.9 -C.sub.10 is a CC-single bond, as well as the acid addition salts thereof. The compounds exhibit valuable pharmacological properties.
    Type: Grant
    Filed: October 6, 1986
    Date of Patent: October 17, 1989
    Assignee: Schering Aktiengesellschaft
    Inventors: Andreas Huth, Gerhard Sauer, Helmut Wachtel
  • Patent number: 4870179
    Abstract: A method of preparing lysergol derivatives, particularly 10.alpha.-methoxy lumilysergol, 1-methyl-10.alpha.-methoxy-lumilysergol and C8 esters of 1-methyl-10.alpha.-methoxy-lumilysergol, is provided characterized in that lysergol esters are subjected to photo-chemical reaction in methanol/sulphuric acid to form esters of 10.alpha.-methoxy lumilysergol. The esters can be subsequently hydrolyzed to obtain 10.alpha.-methoxy-lumilysergol, or can be transesterified with salts of other acids and/or N-methylated.
    Type: Grant
    Filed: August 7, 1985
    Date of Patent: September 26, 1989
    Assignee: Inverni Della Beffa SpA
    Inventors: Ezio Bomardelli, Giuseppe Mustich
  • Patent number: 4859682
    Abstract: The invention relates to novel 2-halogenated 8- and 1,8-substituted ergolene derivatives of the formula (I) and the acid addition salts thereof, pharmaceutical compositions containing them and a process for their preparation. In the formula (I) ##STR1## wherein X stands for a halogen;R stands for a C.sub.1-4 alkyl group andR" means a hydroxyl group; orR stands for an acyl or substituted acyl group andR" represents a halogen or an --OR' group, whereinR' stands for an acyl or substituted acyl group; orR stands for hydrogen andR" means a halogen or an --OR' group, wherein R' stands for an acyl or substituted acyl group; and the dotted line means a double bond between the 8-9 or 9-10 positions.The compounds of the formula (I) possess an antipsychotic and antihypoxic action and a negligable extrapyramidal side-effect.
    Type: Grant
    Filed: April 21, 1987
    Date of Patent: August 22, 1989
    Assignee: Richter Gedeon Vegyeszeti Gyar Rt.
    Inventors: Tibor Keve, Gabor Megyeri, Bela Stefko, Lajos Kovacs, Jr., Anna Kassai nee Zieger, Bela Kiss, Istvan Laszlovszky, Erzsebet Lapis, Eva Palosi, Dora Groo, Laszlo Szporny
  • Patent number: 4859678
    Abstract: An ergoline derivative of the formula I: ##STR1## wherein R.sub.1 represents hydrogen or a methyl group; R.sub.2 represents hydrogen or a halogen atom, a methyl, cyano or phenyl group or an alkylthio group having from 1 to about 4 carbon atoms; R.sub.3 represents a hydrocarbon group having from 1 to about 4 carbon atoms; R.sub.4 represents hydrogen, a phenyl group or a hydrocarbon group having from 1 to about 4 carbon atoms; wherein either (a) R.sub.6 and R.sub.7 represent a valence bond or hydrogen atoms and R.sub.8 represents a hydrogen atom or a methoxy group, or (b) R.sub.6 represents a hydrogen atom and R.sub.7 and R.sub.8 taken together represent a valence bond; W represents an oxygen atom or an imino group; A represents a group of the formula CHR.sub.5, CH.dbd.CR.sub.5 or CH.sub.2 CHR.sub.5 wherein R.sub.
    Type: Grant
    Filed: June 21, 1988
    Date of Patent: August 22, 1989
    Assignee: Farmitalia Carlo Erba
    Inventors: Sergio Mantegani, Enzo Brambilla, Aldemio Temperilli, Daniela Ruggieri, Patricia Salvati
  • Patent number: 4847262
    Abstract: Novel ergoline derivatives, substituted in the 2-position, of the formula ##STR1## wherein C.sub.8 ---C.sub.9 and C.sub.9 ---C.sub.10 each independently is a CC-single or a C.dbd.C-double bond, but not together a cumulated double bond, and the substituent in the 8-position is in the .alpha.- or .beta.-configuration where C.sub.8 ---C.sub.9 is a CC-single bond,R.sup.2 is a CN, SR, SOR, ##STR2## wherein n is 2 or 3, ##STR3## and --CH(OR)R whereinR has the meaning of H or C.sub.1-4 -alkyl,the grouping COR' and CSR'wherein R'=OH, OC.sub.1-4 -alkyl, benzyl, NH.sub.2 or NHR",the grouping CH.dbd.CH--CO.sub.2 R" and CH.sub.2 --CH.sub.2 --CO.sub.2 R'wherein R"=C.sub.1-4 -alkyl,the grouping C.tbd.C--R'" and HC.dbd.CH--R'"wherein R'"=hydrogen, C.sub.1-4 -alkyl, phenyl, CH.sub.2 OH, CR".sub.2 OH, ##STR4## CO.sub.2 R", CH.sub.2 NR".sub.2 or SiMe.sub.2 R"; C.sub.1-3 -alkyl, or C.sub.1-3 -alkyl substituted by OH or phenyl; or ##STR5## wherein R" is C.sub.1-4 alkyl, R.sup.6 is C.sub.1-4 -alkyl andR.sup.
    Type: Grant
    Filed: December 22, 1987
    Date of Patent: July 11, 1989
    Assignee: Schering Aktiengesellschaft
    Inventors: Gerhard Sauer, Andreas Huth, Helmut Wachtel, Herbert H. Schneider
  • Patent number: 4843073
    Abstract: t-Alkyl ergoline derivatives of formula I are produced ##STR1## wherein (R.sub.1 =H, OCH.sub.3 and R.sub.2 =H) or (R.sub.1 +R.sub.2 =a ring bond and R.sub.3 =H, optionally substituted nicotinoyl or 1-oxo-2-cyclopenten-3-yl); and their pharmaceutically acceptable salts.A process for the preparation of these derivatives from lysergol and a t-alkyl alcohol is also described, as are pharmaceutical compositions containing them.
    Type: Grant
    Filed: June 23, 1987
    Date of Patent: June 27, 1989
    Assignee: Farmitalia Carlo Erba S.p.A.
    Inventors: Aldemio Temperilli, Enzo Brambilla, Mauro Gobbini, Maria A. Cervini
  • Patent number: 4839363
    Abstract: Ergoline derivatives of the formula I ##STR1## wherein R.sub.1 represents a hydrogen atom or a methyl group; R.sub.2 represents a hydrogen atom or a methoxy group;R.sub.3 represents a hydrocarbon group having from 1 to 4 carbon atoms;X represents a nitrogen atom and Y represents an oxygen atom, a ##STR2## group wherein R.sub.4 represents a hydrogen atom, a C.sub.1 -C.sub.4 alkyl or a phenyl group, R.sub.5 represents a hydrogen atom, a C.sub.1 -C.sub.4 alkyl, a phenyl, an amino or di(C.sub.1 -C.sub.4 alkyl)amino group and the nitrogen atom of the group ##STR3## is not joined to the nitrogen atom represented by X, or Y represents a nitrogen atom and X represents an oxygen atom or a ##STR4## group wherein R.sub.4 is as above defined; and the pharmaceutically acceptable salt thereof; are useful for treatment of Parkinsonism and dyskinetic symptoms.
    Type: Grant
    Filed: January 27, 1988
    Date of Patent: June 13, 1989
    Assignee: Farmitalia Carlo Erba
    Inventors: Enzo Brambilla, Sergio Mantegani, Lorenzo Pegrassi, Alessandro Rossi, Aldemio Temperilli