Having -c(=x)-, Wherein X Is Chalcogen, Bonded Directly To The Tropane Ring System Patents (Class 546/132)
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Publication number: 20040116703Abstract: The present invention relates to novel 8-azabicyclo[3.2.1]oct-2-ene and -octane derivatives which are found to be cholinergic ligands at the nicotinic Acetyl Choline Receptors.Type: ApplicationFiled: December 4, 2003Publication date: June 17, 2004Applicant: NEUROSEARCH A/SInventors: Dan Peters, Gunnar M. Olsen, Simon Feldbaek Nielsen, Elsebet Ostergaard Nielsen
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Patent number: 6706880Abstract: The invention relates to novel compounds which show high affinity for cocaine receptors in the brain, particularly dopamine and serotonin transporter sites. The compounds may be used as imaging or pharmaceutical agents, in the diagnosis and treatment of drug addiction, depression, anorexia and neurodegenerative diseases or in determining the doses of therapeutic agents that occupy significant numbers of receptors.Type: GrantFiled: September 20, 2001Date of Patent: March 16, 2004Assignee: Research Triangle InstituteInventors: Frank I. Carroll, Michael J. Kuhar, John W. Boja, Anita H. Lewin, Philip Abraham
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Publication number: 20040030134Abstract: A novel process is provided for the preparation of chiral intermediates useful in the asymmetric syntheses of &agr;v&bgr;3 integrin receptor antagonists. Also provided are the enantiomerically enriched intermediates that are obtained from the process.Type: ApplicationFiled: September 11, 2003Publication date: February 12, 2004Inventors: James Christopher McWilliams, Elizabeth Buck, Kan K. Eng, Guy R. Humphrey, Peter E. Maligres, Jess W. Sager, Marjorie See Waters
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Patent number: 6670375Abstract: New tropane analogs that bind to monoamine transporters are described, particularly, 8-aza, 8carbo and 8-oxo tropanes having 6- or 7-substituents. The compounds of the present invention can be racemic, pure R-enantiomers, or pure S-enantiomers. Certain preferred compounds of the present invention have a high selectivity for the DAT versus the SERT. Also described are pharmaceutical therapeutic compositions comprising the compounds formulated in a pharmaceutically acceptable carrier and a method for inhibiting 5-hydroxy-tryptamine reuptake of a monoamine transporter by contacting the monoamine transporter with a 5-hydroxytryptamine reuptake inhibiting amount of a compound of the present invention. Preferred monoamine transporters for the practice of the present invention include the dopamine transporter, the serotonin transporter and the norepinephrine transporter.Type: GrantFiled: June 6, 2001Date of Patent: December 30, 2003Assignees: Organix, Inc., President and Fellows of Harvard CollegeInventors: Peter C. Meltzer, Bertha K. Madras, Paul Blundell, Zhengming Chen
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Patent number: 6645977Abstract: The present invention discloses compounds of formula (1) any of its enantiomers or any mixture thereof, or a pharmaceutically acceptable salt thereof; wherein - - - - is a single or a double bond; R is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; and R1 is (a), wherein R2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, amino; or aryl which may be substituted one or more times with substituents selected from the group consisting of alkyl, cycloalklyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, thioalkoxy, thiocycloalkoxy, methylenedioxy, aryloxy, halogen, CF3, OCF3, CN, amino, aminoacyl, nitro, aryl and a monocyclic 5 to 6-membered heteroaryl group; a monocyclic 5 to 6-membered heteroaryl group which may be substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, thioalkoxy, thiocycloalkoxy, methylenedioxy, aryloxy, halogen,Type: GrantFiled: November 29, 1999Date of Patent: November 11, 2003Assignee: NeuroSearch A/SInventors: Dan Peters, Gunnar M. Olsen, Simon Feldbaek Nielsen, Elsebet Ostergaard Nielsen
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Publication number: 20030203934Abstract: A class of binding ligands for cocaine receptors and other receptors in the brain. Specifically, a novel family of compounds shows high binding specificity and activity, and, in a radiolabeled form, can be used to bind to these receptors, for biochemical assays and imaging techniques. Such imaging is useful for determining effective doses of new drug candidates in human populations. In addition, the high specificity, slow onset and long duration of the action of these compounds at the receptors makes them particularly well suited for therapeutic uses, for example as substitute medication for psychostimulant abuse. Some of these compounds may be useful in treating Parkinson's Disease or depression, by virtue of their inhibitory properties at monoamine transporters.Type: ApplicationFiled: October 25, 2002Publication date: October 30, 2003Applicant: Research Triangle InstituteInventors: Michael J. Kuhar, Frank I. Carroll, John W. Boja, Anita H. Lewin, Philip Abraham
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Publication number: 20030144317Abstract: This invention provides a method for preparing a benzoylecgonine composition comprising the steps of:Type: ApplicationFiled: November 13, 2002Publication date: July 31, 2003Inventor: Nicholas James Archer
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Publication number: 20030109708Abstract: The present invention relates to a process for synthesizing an anhydroecgonine derivative without using cocaine as a starting material, and a process for synthesizing a phenyltropane derivative by using said anhydroecgonine derivative as an intermediate for the synthesis.Type: ApplicationFiled: August 2, 2002Publication date: June 12, 2003Applicant: NIHON MEDI-PHYSICS CO., LTD.Inventors: Kyoko Okano, Osamu Itoh
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Publication number: 20030065183Abstract: An optically active tropinonemonocarboxylic acid ester derivative useful as an intermediate for synthesis of optically active tropane derivatives was obtained by reacting succindialdehyde with an organic amine and acetonedicarboxylic acid ester to obtain a tropinonedicarboxylic acid ester derivative, and then subjecting this derivative to enzyme-catalyzed asymmetric dealkoxy-carbonylation. Since anhydroecgonine methyl ester derived from the optically active tropinone-monocarboxylic acid ester derivative by reduction and dehydration had the same direction of optical rotation as in the case of anhydroecgonine methyl ester obtained from natural cocaine, it was proved that the obtained optically active tropinonemonocarboxylic acid ester derivative had the same absolute configuration as that of natural cocaine. The yield of the optically active tropinonemonocarboxylic acid ester derivative from the asymmetric dealkoxycarbonylation was 30 to 50 mol %, and its optical purity was 70 to 97% ee.Type: ApplicationFiled: September 26, 2002Publication date: April 3, 2003Applicant: NIHON MEDI-PHYSICS CO., LTD.Inventors: Manabu Node, Soichi Nakamura, Daisaku Nakamura
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Patent number: 6537522Abstract: Iodinated neuroprobes for mapping monoamine reuptake sites in the brain, and particularly iodinated neuroprobes that can also serve as radiotracers for use in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) for imaging of such reuptake sites, are disclosed. Precursors of radiolabeled iodinated neuroprobes, both with and without a radiotracer atom, and kits for preparing the radiolabeled iodinated neuroprobes are also disclosed.Type: GrantFiled: May 12, 1998Date of Patent: March 25, 2003Assignee: Amersham PLCInventors: John L. Neumeyer, Richard A. Milius, Robert B. Innis, Gilles Tamagnan, Shaoyin Wang
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Patent number: 6531483Abstract: The invention relates to novel compounds which show high affinity for cocaine receptors in the brain, particularly dopamine and serotonin transporter sites. The compounds may be used as imaging or pharmaceutical agents, in the diagnosis and treatment of drug addiction, depression, anorexia and neurodegenerative diseases.Type: GrantFiled: September 4, 1996Date of Patent: March 11, 2003Assignee: Research Triangle InstituteInventors: Michael J. Kuhar, Frank I. Carroll, John W. Boja, Anita H. Lewin, Philip Abraham
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Publication number: 20020188003Abstract: Tropane derivatives having a high binding affinity and selectivity for dopamine transporters bear, on the tropane backbone either a carboxylic ester or isoxazole moiety, as well as a substituted phenyl moiety. The compounds have utility both as pharmaceutical and as imaging agents, when one or more atoms are radioactive.Type: ApplicationFiled: May 28, 2002Publication date: December 12, 2002Applicant: Research Triangle InstituteInventors: Michael J. Kuhar, Frank Ivy Carroll, John W. Boja, Anita H. Lewin, Philip Abraham
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Patent number: 6399042Abstract: A series of compounds in the 4-fluoroalkyl-3-halophenyl nortropanes family are described as diagnostic and therapeutic agents for diseases associated with serotonin transporter dysfunction. These compounds bind to serotonin transporter protein with high affinity and selectivity. The invention provides methods of synthesis which incorporate radioisotopic halogens at a last step which permit high radiochemical yield and maximum usable product life. The radiolabeled compounds of the invention are useful as imaging agents for visualizing the location and density of serotonin transporter by PET and SPECT imaging.Type: GrantFiled: April 26, 2000Date of Patent: June 4, 2002Assignee: Emory UniversityInventors: Mark M. Goodman, Ping Chen
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Patent number: 6383490Abstract: An anti-cocaine vaccine employs a cocaine hapten conjugated to a carrier protein. The anti-cocaine vaccine elicits an immune response which reduces the psychoactive effects of cocaine consumption by the production of anti-cocaine polyclonal antibodies. The antibodies may be employed in an ELISA test for assaying cocaine. The immune response elicited by the anti-cocaine vaccine produces antibody producing cells which may be isolated and cloned for producing anti-cocaine monoclonal antibodies.Type: GrantFiled: June 12, 1998Date of Patent: May 7, 2002Assignee: The Scripps Research InstituteInventors: Peter Wirsching, Kim D. Janda
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Patent number: 6358492Abstract: The 3&agr; isomer of RTI-55, RTI-352, is an effective in vivo binding ligand that reflects greater selectivity for the dopamine transporter than is observed with RTI-55. In addition, there is also a more rapid achievement of apparent equilibrium in the striatal-to-cerebellar ratio (compared to RTI-55) as the ratio peaks at about 30 min and is maintained for about 20 min thereafter. Such apparent equilibrium is useful in developing an approach to measuring the number of dopamine transporters present in tissues. Moreover, these results indicate that the utilization of 3&agr; isomers of a variety of 3&bgr;-(substituted phenyl)tropanes will result in greater selectivity for dopamine transporters and a more rapid of achievement of apparent equilibrium.Type: GrantFiled: October 7, 1997Date of Patent: March 19, 2002Assignee: Research Triangle InstituteInventors: Michael J. Kuhar, Frank I. Carroll, John W. Boja, Anita H. Lewin, Philip Abraham
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Patent number: 6350758Abstract: A compound of formula (I) wherein R1-R6 have any of the values defined in the specification are described, as well as pharmaceutical compositions comprising a compound of formula (I), and methods for preparing and using compounds of formula (I) are described.Type: GrantFiled: September 14, 1999Date of Patent: February 26, 2002Assignee: Georgetown UniversityInventors: Alan P. Kozikowski, Gian Luca Araldi
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Patent number: 6344179Abstract: Provided are compounds of the following formula: wherein R is C2-C6 mono- or multi-unsaturated hydrocarbon having one or more ethylene, acetylene or allene groups, A is 18 or 19, and X is H or halogen. The compounds of the invention bind to dopamine transporter with high affinity and selectivity and are thus useful as diagnostic and therapeutic agents for diseases associated with dopamine transporter dysfunction. The radiolabeled compounds are useful as imaging agents for visualizing the location and density of dopamine transporter by PET imaging.Type: GrantFiled: April 21, 2000Date of Patent: February 5, 2002Assignee: Emory UniversityInventors: Mark M. Goodman, Ping Chen
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Patent number: 6329520Abstract: The invention relates to novel compounds which show high affinity for cocaine receptors in the brain, particularly dopamine and serotonin transporter sites. The compounds may be used as imaging or pharmaceutical agents, in the diagnosis and treatment of drug addiction, depression, anorexia and neurodegenerative diseases or in determining the doses of therapeutic agents that occupy significant numbers of receptors.Type: GrantFiled: May 22, 1998Date of Patent: December 11, 2001Assignee: Research Triangle InstituteInventors: Frank I. Carroll, Michael J. Kuhar, John W. Boja, Anita H. Lewin, Philip Abraham
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Patent number: 6316624Abstract: A process for preparing a compound of formula (IV) wherein R1 is C1-4 alkyl, C1-4 haloalkyl, benzyl, C3-6 alkenyl or C3-6 alkyny, (provided that the &agr;-carbon atom of R1 is neither unsaturated nor substituted with halogen), which comprises reacting a compound of formula (III) with a source of hydroxylamine in the presence of an acid. Compounds of formula (IV) are agrochemical intermediates.Type: GrantFiled: May 30, 2000Date of Patent: November 13, 2001Assignee: Syngenta Ltd.Inventors: Martin Charles Bowden, Stephen Martin Brown
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Publication number: 20010020096Abstract: The present invention relates to a process for synthesizing an anhydroecgonine derivative without using cocaine as a starting material, and a process for synthesizing a phenyltropane derivative by using said anhydroecgonine derivative as an intermediate for the synthesis.Type: ApplicationFiled: February 2, 2001Publication date: September 6, 2001Inventors: Kyoko Okano, Osamu Itoh
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Patent number: 6241963Abstract: This invention presents a series novel tropane-based derivatives complexed with either technetium or rhenium that are specific for central nervous system receptors, in particular, dopamine or serotonin receptors. The compounds of the invention have utility, inter alia, as imaging agents for CNS receptors. Methods of using these novel compounds as imaging agents are presented, as are intermediates and methods for making these novel compounds.Type: GrantFiled: May 17, 1996Date of Patent: June 5, 2001Assignee: The Trustees of the University of PennsylvaniaInventors: Hank Kung, Sanath Meegalla, Mei-Ping Kung, Karl Plossl
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Patent number: 6221879Abstract: Compounds of general formula (I) in which U represents a group of general formula (A) or (B) in which formulae V represents a hydrogen or halogen atom, a (C1-C3)alkyl group or one or two (C1-C3)alkoxy groups, W and X each represent, respectively, either two oxygen atoms, or an oxygen atom and a CH2 group, or a CH2 group and an oxygen atom, or an oxygen atom and a CO group, n represents the number 0 or 1, R represents either a propyl group when U represents a group of general formula (A), or a hydrogen atom or a (C1-C3)alkyl group when U represents a group of general formula (B), Y represents one or more atoms or groups chosen from the following: hydrogen, halogen, (C1-C3)alkyl and (C1-C3)alkoxy, Z represents two hydrogen atoms or an oxygen atom.Type: GrantFiled: July 14, 2000Date of Patent: April 24, 2001Assignee: Sanofi-SynthelaboInventors: Benoit Marabout, Mireille Sevrin, Pascal George, Jean-Pierre Merly, Daniele De Peretti, Jocelyne Roy, David Machnik
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Patent number: 6180083Abstract: The present invention relates to tropane derivatives having particular use for the in vivo detection of dopamine transporters. These derivatives meet the formula in which R1 is I or Sn (R3)3, R2 is for example the methyl group, and X and Y are various substituents. The derivatives with X═CH3 and Y═H show strong specificity for the dopamine transporter compared with the serotonin transporter (74% inhibition when the transporter is previously saturated with GBR 12909).Type: GrantFiled: November 10, 1998Date of Patent: January 30, 2001Assignee: CIS bio InternationalInventors: Laurent Mauclaire, Patrick Emond, Denis Guilloteau, Jean-Claude Besnard, Yves Frangin
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Patent number: 6171576Abstract: Radiopharmaceutical compounds are disclosed. A tropane compound is linked through the N atom at the 8-position to a chelating ligand capable of complexing technetium or rhenium to produce a neutral labeled complex that selectively binds to the dopamine transporter. These compounds can be prepared as separate diastereoisomers as well as a mixture of diastereoisomers. Also disclosed are radiopharmaceutical kits for preparing the labeled radiopharmaceutical compounds.Type: GrantFiled: November 3, 1995Date of Patent: January 9, 2001Assignees: Organix Inc., President & Fellows of Harvard College, Massachusetts Institute of TechnologyInventors: Peter C. Meltzer, Bertha K. Madras, Alan Davison, Paul Blundell, Ashfaq Mahmood, Alun G. Jones
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Patent number: 6123917Abstract: An improved method for preparation of cocaine receptor binding ligands is provided. The method calls for the preparation of the silylaryl intermediate prepared from phenyl trimethylsilane and a anhydroecgonine methyl ester appropriately substituted. The intermediate is prepared in high purity and can be directly converted to the binding ligand by iodine substitution.Type: GrantFiled: July 31, 1995Date of Patent: September 26, 2000Assignee: Research Triangle InstituteInventor: Frank Ivy Carroll
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Patent number: 6054127Abstract: Hapten-carrier conjugates capable of eliciting anti-hapten antibodies in vivo are disclosed. Methods of preparing the hapten-carrier conjugates and therapeutic compositions are also disclosed. Where the hapten is a drug of abuse, a therapeutic composition containing the hapten-carrier conjugate is particularly useful in the treatment of drug addiction, more particularly, cocaine addiction. Passive immunization using antibodies raised against conjugates of the instant invention is also disclosed. The therapeutic composition is suitable for co-therapy with other conventional drugs.Type: GrantFiled: June 27, 1997Date of Patent: April 25, 2000Assignee: Immulogic Pharmaceutical CorporationInventors: Philip A. Swain, Victoria C. Schad, Julia L. Greenstein, Mark A. Exley, Barbara S. Fox, Stephen P. Powers, Malcolm L. Gefter, Thomas J. Briner
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Patent number: 6054465Abstract: The present invention relates to novel compounds of the Formula I which have hemoregulatory activities and can be used to stimulate hematopoiesis and for the treatment of viral fungal and bacterial infectious diseases.Type: GrantFiled: May 12, 1998Date of Patent: April 25, 2000Assignee: SmithKline Beecham CorporationInventors: Pradip Kumar Bhatnagar, Dirk Andries Heerding
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Patent number: 6013242Abstract: Biologically active derivatives of the tropane ring system are provided which selectively bind either to the 5-HT or DA reuptake site, leading to compounds which have use for the treatment of clinical depression, attention deficit disorder, obesity and cocaine addiction.Type: GrantFiled: January 13, 1998Date of Patent: January 11, 2000Assignees: Wake Forest University, The Research Foundation of State University of New YorkInventors: Huw M. L. Davies, Norman Kong, Steven R. Childers
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Patent number: 5990312Abstract: The present invention discloses compounds of the formula any mixture thereof, or a pharmaceutically acceptable salt thereof;wherein R, R.sup.3, and R.sup.4 each have the meanings set forth in the specification.The compounds possess valuable pharmaceutical properties as dopamine reuptake inhibitors.Type: GrantFiled: November 4, 1997Date of Patent: November 23, 1999Assignee: Neurosearch A/SInventor: Peter Moldt
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Patent number: 5980860Abstract: This invention presents a series of novel tropane-based derivatives complexed with either technetium or rhenium that are specific for central nervous system receptors, in particular, dopamine or serotonin receptors. The compounds of the invention have utility, inter alia, as imaging agents for CNS receptors.Type: GrantFiled: July 16, 1998Date of Patent: November 9, 1999Assignee: The Trustees of University of PennsylvaniaInventors: Hank Kung, Sanath Meegalla, Mei-Ping Kung
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Patent number: 5958945Abstract: The invention pertains to novel azabicyclo-naphthalene-carboxamide derivatives, a method for preparing same and the use thereof as a medicament. The compounds of the invention are of formula (I).Type: GrantFiled: March 12, 1998Date of Patent: September 28, 1999Assignee: Pierre Fabre MedicamentInventors: Thierry Imbert, Barbara Monse, Wouter Koek
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Patent number: 5935953Abstract: The invention relates to a method of controlling an invertebrate pest, comprising contacting the pest with a pest-controlling amount of an agent having substantial inhibitory activity toward a phenylethanolamine reuptake transporter as determined by radioactive octopamine reuptake inhibition assay is disclosed. Compositions comprising compounds capable of inhibiting the octopamine reuptake transporter include cocaine analogs. A process for inhibiting the feeding of an invertebrate pest comprising contacting said pest with a pest-controlling amount of an agent having substantial inhibitory activity toward a phenylethanolamine reuptake transporter as determined by radioactive octopamine reuptake inhibition assay, with the proviso that said agent is not cocaine. A process for delaying the maturation of a juvenile invertebrate by contacting it with an inhibitory amount of a phenylethanolamine reuptake transporter blocker is also disclosed.Type: GrantFiled: March 25, 1997Date of Patent: August 10, 1999Assignee: Research Triangle InstituteInventors: Michael J. Kuhar, Frank I. Carroll, John W. Boja, Anita H. Lewin, Philip Abraham
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Patent number: 5888475Abstract: Novel methods for positron emission tomography or single photon emission spectroscopy using tracer compounds having the structure: ##STR1## where X in .beta. configuration isphenyl, naphthyl; 2,3 or 4-iodophenyl; 2,3 or 4-(trimethylsilyl)phenyl; 3,4,5 or 6-iodonaphthyl; 3,4,5 or 6-(trimethylsilyl)naphthyl; 2,3 or 4-(trialkylstannyl)phenyl; or 3,4,5 or 6-(trialkylstannyl)napthylY in .beta. configuration is2-fluoroethoxy, 3-fluoropropoxy, 4-fluorobutoxy, 2-fluorocyclopropoxy, 2 or 3-fluorocyclobutoxy, R,S 1'-fluoroisopropoxy, R 1'-fluoroisopropoxy, S 1'-fluoroisopropoxy, 1',3'-difluoroisopropoxy, R,S 1'-fluoroisobutoxy, R 1'-fluoroisobutoxy, S 1'-fluoroisobutoxy, R,S 4'-fluoroisobutoxy, R 4'-fluoroisobutoxy, S 4'-fluoroisobutoxy, or 1',1'-di(fluoromethyl)isobutoxy,The compounds bind dopamine transporter protein and can be labeled with .sup.18 F or .sup.123 I for imaging.Type: GrantFiled: October 10, 1997Date of Patent: March 30, 1999Assignee: Emory UniversityInventors: Mark M. Goodman, Bing Zhi Shi, Robert N. Keil
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Patent number: 5876727Abstract: Hapten-carrier conjugates capable of eliciting anti-hapten antibodies in vivo are disclosed. Methods of preparing the hapten-carrier conjugates and therapeutic compositions are also disclosed. Where the hapten is a drug of abuse, a therapeutic composition containing the hapten-carrier conjugate is particularly useful in the treatment of drug addiction, more particularly, cocaine addiction. Passive immunization using antibodies raised against conjugates of the instant invention is also disclosed. The therapeutic composition is suitable for co-therapy with other conventional drugs.Type: GrantFiled: September 30, 1996Date of Patent: March 2, 1999Assignee: ImmuLogic Pharmaceutical CorporationInventors: Philip A. Swain, Victoria C. Schad, Julia L. Greenstein, Mark A. Exley, Barbara S. Fox, Stephen P. Powers, Malcolm L. Gefter
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Patent number: 5864038Abstract: Novel compounds having the structure: ##STR1## where X in .beta. configuration is phenyl, naphthyl; 2,3 or 4-iodophenyl; 2,3 or 4-(trimethylsilyl)phenyl; 3,4,5 or 6-iodonaphthyl; 3,4,5 or 6-(trimethylsilyl)naphthyl; 2,3 or 4-(trialkylstannyl)phenyl; or 3,4,5 or 6-(trialkylstannyl)naphthylY in .beta. configuration is Y.sub.1 or Y.sub.2,whereY.sub.1 is 2-fluoroethoxy, 3-fluoropropoxy, 4-fluorobutoxy, 2-fluorocyclopropoxy, 2 or 3-fluorocyclobutoxy, R,S 1'-fluoroisopropoxy, R 1'-fluoroisopropoxy, S 1'-fluoroisopropoxy, 1',3'-difluoroisopropoxy, R,S 1'-fluoroisobutoxy, R 1'-fluoroisobutoxy, S 1'-fluoroisobutoxy, R,S 4'-fluoroisobutoxy, R 4'-fluoroisobutoxy, S 4'-fluoroisobutoxy, or 1',1'-di(fluoromethyl)isobutoxy, andY.sub.Type: GrantFiled: August 17, 1995Date of Patent: January 26, 1999Assignee: Emory universityInventors: Mark M. Goodman, Bing Zhi Shi, Robert N. Keil
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Patent number: 5834484Abstract: Cocaine analogs are disclosed. The analogs, certain 6-alkyl substituted tropane derivatives, bind to the cocaine binding site on dopamine transporter, without interfering with the dopamine receptor. The craving for cocaine is thereby blocked. The analogs may readily be synthesized stereoselectively, and are relatively resistant to metabolic degradation.Type: GrantFiled: March 9, 1998Date of Patent: November 10, 1998Assignee: Board of Supervisors of Louisiana State University and Agricultural and Mechanical CollegeInventors: Mark L. Trudell, Stacey A. Lomenzo
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Patent number: 5821249Abstract: Methylecgonidine (MEG; anhydroecgonine methylester), is produced when cocaine base ("crack") is heated. MEG alone and in combination with cocaine was tested for action on isolated tracheal rings stimulated to contact with acetylcholine. At micromolar concentrations, cocaine sensitized tracheal rings, increasing both the potency and efficacy of acetylcholine-induced contraction. Surprisingly, MEG, at nanomolar concentrations and above, non-competitively and irreversibly antagonized acetylcholine-induced contraction independently of the actions of cocaine. MEG also displayed antihistaminic activity. Therefore, MEG and anticholinergically active derivatives or analogues thereof are useful in the prevention or treatment of a disease or disorder treatable by an antimuscarinic anticholinergic agent, an anti-histaminic agent or a spasmolytic agent, in particular bronchoconstriction in a number of pulmonary diseases such as asthma.Type: GrantFiled: August 30, 1996Date of Patent: October 13, 1998Assignee: University of RochesterInventors: Ronald W. Wood, Hassan A. N. El-Fawal, John F. Graefe, Lung C. Chen, Jalil Shojaie
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Patent number: 5736123Abstract: Novel compounds useful as intermediates in the synthesis of compounds having high affinity for specific cocaine receptors in the brain have the formula ##STR1## wherein R is (CH.sub.2).sub.n CH.sub.2 Y, and wherein Y is H or F, X is a pharmaceutically acceptable anion, andwherein Sn (R.sup.1, R.sup.2, R.sup.3) is ortho, meta or para and wherein R.sup.1, R.sup.2, R.sup.3 are independently alkyl of 1-6 carbon atoms and n is an integer of 0-5.Type: GrantFiled: May 8, 1995Date of Patent: April 7, 1998Assignee: Research Triangle InstituteInventor: Frank I. Carroll
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Patent number: 5736556Abstract: The present invention discloses compounds of the formula, ##STR1## any mixture thereof, or a pharmaceutically acceptable salt thereof; wherein R, R.sup.3, and R.sup.4 each have the meanings set forth in the specification.The compounds possess valuable pharmaceutical properties as monoamine neurotransmitter, i.e dopamine, serotonin, noradrenalin, reuptake inhibitors.Type: GrantFiled: October 11, 1996Date of Patent: April 7, 1998Assignee: NeuroSearch A/SInventors: Peter Moldt, Frank Watjen, J.o slashed.rgen Scheel-Kruger
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Patent number: 5591854Abstract: A process of enantioselective synthesis of seven-membered carbocycles in the presence of di-rhodium(II) tetracarboxylate catalysts.Type: GrantFiled: October 14, 1994Date of Patent: January 7, 1997Assignee: Wake Forest UniversityInventor: Huw M. L. Davies
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Patent number: 5585492Abstract: The present invention provides compounds of the formula Ar.sup.1 --Q--Ar.sup.2 --Y--R--Z and pharmaceutically acceptable salts thereof wherein Ar.sup.1 and Ar.sup.2 are optionally substituted aryl moieties, Z is an optionally substituted nitrogen-containing moiety which may be an acyclic, cyclic or bicyclic amine or an optionally substituted monocyclic or bicyclic nitrogen-containing heteroaromatic moiety; Q is a linking group capable of linking two aryl groups; R is an alkylene moiety; Y is a linking moiety capable of linking an aryl group to an alkylene moiety and wherein Z is bonded to R through a nitrogen atom. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of inflammatory diseases which are mediated by LTB.sub.4 production, such as psoriasis, ulcerative colitis, IBD and asthma.Type: GrantFiled: October 11, 1994Date of Patent: December 17, 1996Assignee: G. D. Searle & Co.Inventors: Nizal S. Chandrakumar, Barbara B. Chen, Michael Clare, Bipinchandra N. Desai, Stevan W. Djuric, Stephen H. Docter, Alan F. Gasiecki, Richard A. Haack, Chi-Dean Liang, Julie M. Miyashiro, Thomas D. Penning, Mark A,. Russell, Stella S. Yu
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Patent number: 5552407Abstract: Methylecgonidine (MEG; anhydroecgonine methylester), is produced when cocaine base ("crack") is heated. MEG alone and in combination with cocaine was tested for action on isolated tracheal rings stimulated to contact with acetylcholine. At micromolar concentrations, cocaine sensitized tracheal rings, increasing both the potency and efficacy of acetylcholine-induced contraction. Surprisingly, MEG, at nanomolar concentrations and above, non-competitively and irreversibly antagonized acetylcholine-induced contraction independently of the actions of cocaine. MEG also displayed antihistaminic activity. Therefore, MEG and anticholinergically active derivatives or analogues thereof are useful in the prevention or treatment of a disease or disorder treatable by an antimuscarinic anticholinergic agent, an anti-histaminic agent or a spasmolytic agent, in particular bronchoconstriction in a number of pulmonary diseases such as asthma.Type: GrantFiled: June 11, 1993Date of Patent: September 3, 1996Assignee: New York University Medical CenterInventors: Ronald W. Wood, Hassan A. N. El-Fawal, John F. Graefe, Lung C. Chen, Jalil Shojaie
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Patent number: 5496953Abstract: Novel compounds show high affinity for specific cocaine receptors in the brain, particularly dopamine transporter sites, and have the formula ##STR1## Wherein Y=CONRR.sub.2, R.sub.1 =hydrogen, C.sub.1-5 alkyl,X=H, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.1-4 alkoxy, C.sub.1-6 alkynyl, halogen, amino, acylamido,R and R.sup.2 may be saturated or unsaturated substituents of 1-6 carbon atoms, aromatic, or combine to form pyrrolidinyl, morpholinyl or piperidinyl moieties, andZ=H, I, Br, Cl, F, CN, CF.sub.3 NO.sub.2, N.sub.3, OR.sub.1, CO.sub.2 NH.sub.2, CO.sub.2 R.sub.1, C.sub.1-6 alkyl, NR.sub.4 R.sub.5, NHCOF.sub.5, NHCO.sub.2 R.sub.6,wherein R.sub.4 -R.sub.6 are each C.sub.1-6 alkyl.Type: GrantFiled: December 10, 1993Date of Patent: March 5, 1996Assignee: Research Triangle InstituteInventors: Michael J. Kuhar, Frank I. Carroll, Joh W. Boja, Anita H. Lewin, Philip Abraham
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Patent number: 5416092Abstract: Non-peptidyl compounds characterized generally as .alpha.-succinamidoacyl aminodiols having a 3-azabicyclo[3.2.1]-oct-8-yl-type group at the N-terminus are useful as renin inhibitors for the treatment of hypertension.Type: GrantFiled: January 25, 1994Date of Patent: May 16, 1995Assignee: G. D. Searle & Co.Inventors: Gunnar J. Hanson, John S. Baran
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Patent number: 5413779Abstract: 3.beta.-[4-iodophenyl]-tropan-2.beta.-carboxylic acid methyl ester tartrate is a high affinity binding ligand for cocaine receptors in mammalian brains. It and its congeners may be employed for imaging and other brain scanning techniques that allow the determination of the presence of cocaine receptors, such as dopamine and serotonin transporters and the like.Type: GrantFiled: March 23, 1993Date of Patent: May 9, 1995Assignees: Research Triangle Institute, The United States of America represented by the Secretary of Health and Human ServicesInventors: Michael J. Kuhar, Frank I. Carroll, John W. Boja, Anita H. Lewin, Philip Abraham
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Patent number: 5380848Abstract: Novel compounds show high affinity for specific cocaine receptors in the brain, particularly dopamine transporter sites, and have the formula ##STR1## Wherein Y=CH.sub.2 R.sub.3, CO.sub.2 R.sub.2 or ##STR2## R.sub.1 =hydrogen, C.sub.1-5 alkyl, R.sub.2 =hydrogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.1-4 alkoxy, C.sub.1-6 alkynyl, halogen or amine,R.sub.3 =OH, hydrogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.1-4 alkoxy, Cl Br, I, CN, NH.sub.2, NHC.sub.1-6 alkyl, NC.sub.1-6 alkyl, OCOC.sub.1-6 alkyl, OCOC.sub.1-3 alkylaryl,A=S, 0 or NHX=H, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.1-4 alkoxy, C.sub.1-6 alkynyl, halogen, amino, acylamido, andZ=H, I, Br, Cl, F, CN, CF.sub.3 NO.sub.2, N.sub.3, OR.sub.1, CO.sub.2 NH.sub.2, CO.sub.2 R.sub.1, C.sub.1-6 alkyl , NR.sub.4 R.sub.5, NHCOR.sub.5, NHCO.sub.2 R.sub.6,wherein R.sub.4 -R.sub.6 are each C.sub.1-6 alkyl.Type: GrantFiled: April 26, 1994Date of Patent: January 10, 1995Assignees: Research Triangle Institute, The United States of America as represented by the Department of Health and Human ServiesInventors: Michael J. Kuhar, John W. Boja, Frank I. Carroll, Anita H. Lewin, Philip Abraham
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Patent number: 5374636Abstract: The present invention discloses compounds of the formula ##STR1## any mixture thereof, or a pharmaceutically acceptable salt thereof; wherein R, R.sup.3, and R.sup.4 each have the meanings set forth in the specification.The compounds possess valuable pharmaceutical properties as dopamine reuptake inhibitors.Type: GrantFiled: July 16, 1993Date of Patent: December 20, 1994Assignee: NeuroSearch A/SInventors: Peter Moldt, Jorgen Scheel-Kruger, Leif H. Jensen
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Patent number: 5340936Abstract: This invention relates to compounds of the formula ##STR1## where X is --0--, --S--or --NH--;Y is hydrogen, halogen and loweralkoxy;p is 1 or 2;n is 2, 3 or 4;R is hydrogen, loweralkyl, loweralkoxy, hydroxy, halogen, amino, loweralkylamino, nitro, loweralkylthio, trifiuoromethoxy, cyano, trifluoromethyl, ##STR2## where aryl is ##STR3## R.sub.1 is hydrogen, loweralkyl, loweralkoxy, halogen, hydroxy, carboxyl, loweralkylamino, nitro, loweralkylthio, cyano, and trifluoromethyl;m is 1 or 2; a pharmaceutically acceptable acid addition salt thereof and, where applicable the geometric and optical isomers and racemic mixtures thereof.The compounds and compositions of this invention are useful as antipsychotic agent, as 5-HT.sub.3 receptor antagonists and as inhibitors of the reuptake of serotonin.Type: GrantFiled: March 25, 1993Date of Patent: August 23, 1994Assignee: Hoechst-Roussel Pharmaceuticals Inc.Inventors: Edward J. Glamkowski, David M. Fink, Barbara E. Kurys, Yulin Chiang
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Patent number: 5310912Abstract: An iodinated neuroprobe is provided for mapping monoamine reuptake sites. The iodinated neuroprobe is of the formula: ##STR1## wherein R=a C.sub.n H.sub.2n+1 group where n=0-6, an alkenyl group, a monofluoroalkyl group including .sup.n F where n=18 or 19, or a .sup.m C.sub.n H.sub.2n+1 group where n=1-6 and where m=11 or 14 for at least one .sup.m C;R'=a C.sub.n H.sub.2n+1 group where n=0-6, a p-iodophenylmethyl group, a p-iodophenylethyl group, a phenylmethyl group, or a phenylethyl group;X=an isotope of F, an isotope of Cl, an isotope of Br, an isotope of I, CH.sub.3, or Sn(R".sub.1 R".sub.2 R".sub.3);R".sub.1 =a C.sub.n H.sub.2n+1 group where n=1-6, or an aryl group;R".sub.2 =a C.sub.n H.sub.2n+1 group where n=1-6, or an aryl group;R".sub.3 =a C.sub.n H.sub.2n+1 group where n=1-6, or an aryl group; andY=H only if X is an isotope of I, or R' is a p-iodophenylmethyl group, or R' is a p-iodophenylethyl group, else Y=an isotope of I.Related analogs are also provided.Type: GrantFiled: February 25, 1992Date of Patent: May 10, 1994Assignee: Research Biochemicals Limited PartnershipInventors: John L. Neumeyer, Richard A. Milius, Robert B. Innis
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Patent number: 5288872Abstract: Novel tropane ring system compounds useful for treatment of neurological disorders and for synthetic starting materials for production of cocaine analogs.Type: GrantFiled: March 13, 1992Date of Patent: February 22, 1994Assignee: Wake Forest UniversityInventors: Huw M. L. Davies, Elie Saikali