Abstract: This invention relates to di[(1 R)-(-)-camphosulfonic acid) salt of [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.,(S*)]]-4-[7-[[2-(3-chloro-2-thienyl )-1-ethylethyl]amino]3 H-imidazo[4,5-b]pyridin-3-yl]-N-ethyl-2,3-dihydroxycyclopentanecarboxamide , and a process for preparing the compound, comprising reacting a reaction mixture of (-)-1.beta.-N-ethyl-2.alpha.,3.alpha.-isopropylidenedioxy-4.beta.-[3-amino -4-[2-(5-chloro-2-thienyl)-(1R)-1-ethylethyl]amino-2-pyridyl]aminocyclopent anecarboxamide and formamidine acetate, and then treating the reaction mixture with (1 R)-(-)-10-camphorsulfonic acid.The salt is useful in purifying [1 S-[1.alpha.,2.beta.,3.beta.,4.alpha.,(S*)]]-4-[7-[[2-(3-chloro-2-thienyl)- 1-ethylethyl]amino]-3 H-imidazo[4,5-b]pyridin-3-yl]-N-ethyl-2,3-dihydroxycyclopentanecarboxamide which possesses adenosine agonist activity and is useful as an anti-hypertensive, cardioprotective, anti-ischemic, and antilipolytic agent.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
July 29, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Alfred P. Spada, Cynthia A. Fink, Michael R. Myers, Laurence W. Reilly, Benoit J. Vanasse
Abstract: This invention relates to bis mono- and/or bicyclic aryl and/or heteroaryl compounds exhibiting protein tyrosine kinase inhibition activity. More specifically, it relates to the method of inhibiting abnormal cell proliferation in a patient suffering from a disorder characterized by such proliferation comprising the administration thereto of an EGF and/or PDGF receptor inhibiting effective amount of said bis mono- and/or bicyclic aryl and/or heteroaryl compound and to the preparation of said compounds and their use in pharmaceutical compositions used in this method.
Type:
Grant
Filed:
May 11, 1995
Date of Patent:
July 8, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Alfred P. Spada, Michael R. Myers, Martin P. Maguire, Paul E. Persons
Abstract: The compounds of formula I exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More especially, they are Factor Xa inhibitors. The present invention is directed to compounds of formula I, compositions containing compounds of formula I, and their use, which are for treating a patient suffering from, or subject to, conditions which can be ameliorated by the administration of an inhibitor of Factor Xa.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
March 18, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
William R. Ewing, Michael R. Becker, Henry W. Pauls, Daniel L. Cheney, Jonathan S. Mason, Alfred P. Spada
Abstract: Stable, highly purified Factor VIII protein formulations are provided in high ionic strength media which comprises: sodium chloride, potassium chloride or mixtures thereof; calcium chloride; and histidine as the buffering agent.
Type:
Grant
Filed:
December 27, 1994
Date of Patent:
February 25, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Abstract: The present invention relates to a new isoindolinone derivative of formula: ##STR1## in racemic form or in the form of its enantiomers, as well as its salts, its preparation and the pharmaceutical compositions which contain it.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
February 4, 1997
Assignee:
Rhone-Pouelnc Rorer S.A.
Inventors:
Michel Barreau, Michel Cheve, Marie-Christine Dubroeucq, Gilles Dutruc-Rosset, Franco Manfre
Abstract: This invention relates to a class of novel amino bi- and tri-carbocyclic alkane compounds having bis-aryl substitution which exhibit squalene synthase inhibition properties. The bi- and tri-carbocyclic alkane ring contains an amino group and the ring is further linked or bridged to two mono- and/or bicyclic rings. Compounds of this invention reduce levels of serum cholesterol in the body without significantly reducing mevalonic metabolite synthesis. This invention relates also to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention.
Type:
Grant
Filed:
December 7, 1994
Date of Patent:
January 21, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Robert L. Morris, Kent W. Neuenschwander, Keith S. Learn, Anthony C. Scotese
Abstract: This invention relates to a class of novel phosphonate derivatives of lipophilic amines which exhibit squalene synthase inhibition properties. More specifically the compounds are bis aryl cycloalkylamino and azacycloalkyl phosphonates. Compounds of this invention reduce levels of serum cholesterol in the body without significantly reducing mevalonic metabolite synthesis. This invention relates also to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention.
Type:
Grant
Filed:
May 4, 1995
Date of Patent:
October 8, 1996
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Henry W. Pauls, Yong-Mi Choi, Dilip V. Amin
Abstract: This invention relates to a class of novel aliphatic amino bis-aryl compounds containing at least four carbon atoms and an amino group either substituted thereon or incorporated therein and is further linked or bridged to two mono- and/or bicyclic rings. Compounds of this invention reduce levels of serum cholesterol in the body without significantly reducing mevalonic metabolite synthesis. This invention relates also to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention.
Type:
Grant
Filed:
May 22, 1995
Date of Patent:
October 1, 1996
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Robert A. Groneberg, John R. Regan, Kent W. Neuenschwander, Anthony C. Scotese
Abstract: This invention relates to a class of novel dicarboxy amide derivatives of lipophilic amines which exhibit squalene synthase inhibition properties. More specifically the compounds are bis-aryl and/or heteroaryl alkyl or cycloalkylamino dicarboxy amides. Compounds of this invention reduce levels of serum cholesterol in the body without significantly reducing mevalonic metabolite synthesis. This invention relates also to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention.
Type:
Grant
Filed:
December 16, 1994
Date of Patent:
September 17, 1996
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Henry W. Pauls, Yong-Mi Choi, Robert W. Studt, Martin P. Maguire, Alfred P. Spada, Don D. Cha
Abstract: This invention is directed to 1-alkoxy-2-(alkoxy- or cycloalkyloxy-)-4-(cyclothioalkyl- or cyclothioalkenyl-)benzene compounds that inhibit cyclic AMP phosphodiesterase or tumor necrosis factor (TNF) and are useful in treating patients suffering from disease state capable of being modulated by inhibiting production of cyclic AMP phosphodiesterase or TNF by administering the compound to the patient. The invention is also directed to the preparation of these compounds, pharmaceutical compositions containing these compounds and methods for their pharmaceutical use.
Type:
Grant
Filed:
November 3, 1994
Date of Patent:
July 30, 1996
Assignee:
Rhone-Poulenc Rorer Limited
Inventors:
Garry Fenton, Jonathan S. Mason, Malcolm N. Palfreyman, Andrew J. Ratcliffe
Abstract: This invention provides a unique SH3 binding domain core motif of the sequence RPLPXXP and cDNA clones encoding proteins which interact with the SH3 domain of c-src, as well as the amino acid sequences which mediate this binding.Another embodiment of this invention is a method of identifying SH3-binding proteins and elucidating the sequences which mediate binding. This method may be used as an assay to select compounds which bind to this site and which inhibit or enhance the binding of the SH3 domain.
Type:
Grant
Filed:
April 19, 1994
Date of Patent:
July 30, 1996
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
George H. Searfoss, III, Yuri D. Ivashchenko, Michael C. Jaye, Victoria J. South, Stephen M. French, Christopher Cheadle, George A. Ricca
Abstract: This invention relates to a class of novel aliphatic amino bis-aryl compounds containing at least four carbon atoms and an amino group either substituted thereon or incorporated therein and is further linked or bridged to two mono- and/or bicyclic rings. Compounds of this invention reduce levels of serum cholesterol in the body without significantly reducing mevalonic metabolite synthesis. This invention relates also to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention.
Type:
Grant
Filed:
January 25, 1995
Date of Patent:
July 9, 1996
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Robert A. Groneberg, John R. Regan, Kent W. Neuenschwander, Anthony C. Scotese
Abstract: A method of improving the therapeutic activity of von Willebrand Factor obtained from materials comprising said Factor comprising incubating said Factor at a temperature of about 20.degree. C. to about 55.degree. C. for about 1 to about 30 hours.
Type:
Grant
Filed:
May 16, 1994
Date of Patent:
April 9, 1996
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Abstract: The present invention relates to a novel 2-aminonaphthyridine compounds that are useful in preparing a 2-isoindolinyl napthyridine compound that exhibits remarkable anxiolytic, hypnotic, anticonvulsant, antiepileptic and muscle-relaxant properties. The invention is also directed to the optical isomers of the 2-amino napthyridine compounds and salts thereof, their preparation and the use of the 2-amino napthyridine compounds for preparing the 2-isoindolinyl napthyridine compound.
Abstract: The present invention relates to a new isoindolinone derivative of formula: ##STR1## in racemic form or in the form of its enantiomers, as well as its salts, its preparation and the pharmaceutical compositions which contain it.
Type:
Grant
Filed:
August 5, 1994
Date of Patent:
February 27, 1996
Assignee:
Rhone-Poulenc Rorer S.A.
Inventors:
Michel Barreau, Michel Cheve, Marie-Christine Dubroeucq, Gilles Dutruc-Rosset, Franco Manfre
Abstract: This invention relates to polycyclic compounds containing two mono- and/or bicyclic rings and a basic tertiary amino group capable of forming an ammonium ion at biological pH and which reduces levels of serum cholesterol in the body without significantly reducing mevalonic metabolite synthesis. This invention relates also to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention.
Type:
Grant
Filed:
October 7, 1994
Date of Patent:
February 27, 1996
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Kent Neuenschwander, Dilip Amin, Anthony C. Scotese, Robert L. Morris
Abstract: This invention relates to compounds having selective LTB.sub.4 antagonist properties. Therapeutic compositions comprising said compounds and methods for the treatment of disorders involving LTB.sub.4 agonist-mediated activity utilizing said compositions wherein the compounds are described by the formula ##STR1## wherein R.sub.4, X, R, Y, R', Q, m and n are herein defined, and pharmaceutically acceptable salts thereof.
Type:
Grant
Filed:
October 6, 1994
Date of Patent:
February 20, 1996
Assignee:
Rhone-Poulenc Rorer S.A.
Inventors:
Norbert Dereu, Wolfram Hendel, Richard Labaudiniere
Abstract: This invention relates to bis mono- and/or bicyclic aryl and/or heteroaryl compounds exhibiting protein tyrosine kinase inhibition activity. More specifically, it relates to the method of inhibiting abnormal cell proliferation in a patient suffering from a disorder characterized by such proliferation comprising the administration thereto of an EGF and/or PDGF receptor inhibiting effective amount of said bis mono- and/or bicyclic aryl and/or heteroaryl compound and to the preparation of said compounds and their use in pharmaceutical compositions used in this method.
Type:
Grant
Filed:
December 10, 1993
Date of Patent:
January 2, 1996
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Alfred P. Spada, Michael R. Myers, Martin P. Maguire, Paul E. Persons
Abstract: This invention relates to pyrazolo[3,4-g]quinoxaline compounds exhibiting protein tyrosine kinase inhibition activity of the formula: ##STR1## where: ------ may be a double bond;R, R.sub.2, R.sub.3 and R.sub.4 are as described in claim 1;a pharmaceutically acceptable salt thereof.More specifically, compounds of this invention are novel as selective inhibitors of the PDGF-R protein tyrosine kinase and can be applied as potential therapeutic agents for various disease states which are characterized by uncontrolled cellular proliferation. Further, the present invention provides pharmaceutical compositions and a method for treating such disorders comprising the administration to a patient of a PDGF receptor inhibiting effective amount of a pyrazolo[3,4-g]quinoxaline compound exhibiting protein tyrosine kinase inhibition activity. Processes for the preparation of pyrazolo[3,4-g]quinoxaline compounds are also described.
Type:
Grant
Filed:
September 8, 1994
Date of Patent:
December 19, 1995
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals, Inc.
Inventors:
Michael R. Myers, Paul E. Persons, Cuong Q. Ly, Alfred P. Spada