Abstract: Novel derivatives of 1R- or 1S-2-azabicyclo?2.2.1!heptane with the general formula (I) or (I'), preparation and their application. ##STR1## In the general formulas (I) and (I'), R represents a hydrogen atom or a group with the formula ##STR2## respectively, in which R.sub.1 represents an alkyl group containing 1-4 carbon atoms and Ar represents an optionally substituted phenyl or a- or b-naphthyl group.
Abstract: Novel farnesyl transferase inhibitors of general formula (I), ##STR1## the preparation thereof and pharmaceutical compositions containing said inhibitors, are disclosed. In general formula (I), R.sub.1 is Y--S--A.sub.1 (where Y is a hydrogen atom, an amino acid residue, a fatty acid residue, an alkyl or alkoxycarbonyl radical or a radical R.sub.4 --S-- where R.sub.4 is a C.sub.1-4 alkyl radical optionally substituted by a phenyl radical or a radical of general formula (II) ##STR2## wherein A.sub.1, X, X.sub.1, Y.sub.1, R'.sub.1, R.sub.2, R'.sub.2 and R are defined as below, and A.sub.1 is a C.sub.1-4 alkylene radical optionally alpha-substituted in the >C(X.sub.1)(Y.sub.1) grouping by an amino or alkylamino, dialkylamino, alkanoylamino or alkoxycarbonylamino radical); X.sub.1 and Y.sub.1 are each a hydrogen atom or, taken together with the carbon atom to which they are attached, form a >C.dbd.O grouping; R'.sub.1 is hydrogen or a C.sub.1-6 alkyl radical; X is an oxygen or sulphur atom; R.sub.2 is a C.
Type:
Grant
Filed:
January 9, 1998
Date of Patent:
March 30, 1999
Assignee:
Rhone-Poulenc Rorer S.A.
Inventors:
Bernard Baudoin, Christopher Burns, Alain Commercon, Alain Lebrun
Abstract: A method for the preparation of a lactam compound of formula ##STR1## wherein R'.sub.1 and R".sub.1 independently are acyl or aroyl, or taken together form an optionally substituted methylene, and G.sub.1 is hydrogen or an amino protecting group, comprising oxidizing a bis O-protected 1R-2-azadihydroxybicyclo-?2.2.1!heptane compound of formula ##STR2## with about 0.1 mol % to about 1 mol % of RuO.sub.2 or hydrate thereof in the presence of about 3 equivalents of an oxidant to form the lactam compound with an enantiomeric excess of greater than or equal to about 95%.
Type:
Grant
Filed:
June 10, 1997
Date of Patent:
March 23, 1999
Assignee:
Rhone-Poulenc Rorer S.A.
Inventors:
Patrick Leon, Denis Largeau, Thierry Durand, Michael O'Brien, Matthew Powers
Abstract: The present invention relates to azacycloalkylalkanoyl peptides and pseudopeptides which inhibit platelet aggregation and thrombus formation thereby being useful in the prevention and treatment of thrombosis associated with disease states such as myocardial infarction, stroke, peripheral arterial disease, and disseminated intravascular coagulation, to methods for the prevention or treatment of thrombosis in a mammal in need of such therapy comprising the administration of a therapeutically effective amount of such compounds, and to pharmaceutical compositions comprising such compounds.
Type:
Grant
Filed:
May 2, 1996
Date of Patent:
February 2, 1999
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Abstract: Novel farnesyl transferase inhibitors of general formula (I) ##STR1## preparation thereof and pharmaceutical compositions containing same. In general formula (I), R.sub.1 is Y--S--A.sub.1 -- (where Y is a hydrogen atom, an amino acid residue, a fatty acid residue, an alkyl or alkoxycarbonyl radical, or a radical R.sub.4 --S--, where R.sub.4 is a C.sub.1-6 alkyl radical optionally substituted by a phenyl radical, or a radical of general formula (II), ##STR2## wherein A.sub.1, X.sub.1, Y.sub.1, R'.sub.2, R'.sub.2, X.sub.2, Y.sub.2, R.sub.3, R'.sub.3 and R are as defined below, and A.sub.1 is a C.sub.1-4 alkylene radical optionally .alpha.-substituted in the >C(X.sub.1) (Y.sub.1) grouping by an amino, alkylamino, alkanoylamino or alkoxycarbonylamino radical); X.sub.1 and Y.sub.1 are each a hydrogen atom or, taken together with the carbon atom to which they are attached, a >C.dbd.O grouping; R.sub.2 is a straight or branched C.sub.1-4 alkyl radical optionally substituted by a cyclohexyl radical; R'.sub.
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: This invention relates to mixtures of sulfated oligosaccharides which possess antithrombotic properties and are useful for the treatment and prevention of venous and arterial thrombosis, prevention of arterial thrombotic accidents, and in the prevention of thrombosis in surgical equipment, to pharmaceutical compositions including such mixtures, to processes for preparing such mixtures, and to the use of such mixtures in the prevention of thrombosis in surgical equipment.
Abstract: The invention is directed to a compound of formula ##STR1## in which R represents a hydroxyl, alkyloxy, phenylalkyloxy or --NH--CH.sub.2 --COOH radical, R.sub.1 represents a hydrogen atom, an adamantylacetyl, adamantylcarbonyl, norbornylacetyl, norbornylphenoxycarbonyl, benzoyl, nicotinoyl, 4-phenylbenzoyl, 4-tert-butylbenzoyl or 2-pyrrolidinecarbonyl radical or a protective group for an amine functional group, R.sub.2 represents an Arg or Lys residue, R.sub.3 represents an Arg or Lys residue, R.sub.4 represents a Pro residue, m, n and p, which are the identical or different, represent a number equal to 0 or 1, R.sub.5 and R.sub.6 are identical and represent a hydroxyl or methoxy radical and R.sub.7 represents a hydrogen, chlorine, bromine or iodine atom or a nitro radical, or the compound wherein one or a number of peptide bonds between two amino acid residues are replaced by --CH.sub.2 --NH bonds or the peptide bond between the R.sub.2 and R.sub.3 amino acid residues is replaced by a CH.dbd.
Type:
Grant
Filed:
November 19, 1996
Date of Patent:
November 24, 1998
Assignee:
Rhone-Poulenc Rorer S.A.
Inventors:
Francois-Frederic Clerc, Marie-Christine Dubroeucq, Gerard Helynck, Jean Leboul, Jean-Paul Martin
Abstract: This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase.
Type:
Grant
Filed:
June 24, 1997
Date of Patent:
November 24, 1998
Assignee:
Rhone-Poulenc Rorer Limited
Inventors:
Garry Fenton, Andrew David Morley, Malcolm Norman Palfreyman, Andrew James Ratcliffe, Brian William Sharp, Keith Alfred James Stuttle, Sukanthini Thurairatnam, Bernard Yvon Jack Vacher
Abstract: A method for the preparation of a compound of formula ##STR1## wherein R is hydrogen or, respectively, a group of formula ##STR2## R.sub.1 is alkyl; Ar is optionally substituted aryl; andR.sub.3' and R.sub.3" are hydrogen, alkyl or phenyl, or R.sub.3' and R.sub.3" taken together with the carbon atom to which they are attached form cycloalkyl, or salt thereof, comprising acid facilitated acetalizing or ketalizing of a compound of formula ##STR3## wherein R.sub.3' and R.sub.3" are as defined above, and R.sub.4' and R.sub.4" are alkoxy, or taken together with the carbon atom to which they are attached form carbonyl, with a compound of formula ##STR4## wherein * represents an R chirality;R, R.sub.1 and Ar are as defined above, or salt thereof in isopropanol.
Type:
Grant
Filed:
June 10, 1997
Date of Patent:
November 3, 1998
Assignee:
Rhone-Poulenc Rorer S.A.
Inventors:
Patrick Leon, Michael O'Brien, Denis Largeau, Matthew Powers, Ching Tsuei
Abstract: Compounds of formula I ##STR1## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, n, and are as defined herein, their use as antiinflammatory, immunosuppressive, and antiallergic agents, pharmaceutical compositions comprising them, and methods for their preparation comprising irradiating compounds of formula II ##STR2## under an inert atmosphere, in the presence or absence of a compound of formula R.sub.3 --S--S(O).sub.m --R.sub.8, where R.sub.7, R.sub.8, and m are as defined herein, and methods for their preparation comprising oxidizing, reducing, halogenating, or alkylating compounds of formula I are disclosed.
Type:
Grant
Filed:
June 2, 1995
Date of Patent:
September 1, 1998
Assignee:
Rhone-Poulenc Rorer Limited
Inventors:
Michael John Ashton, Sven Jan-Anders Karlsson, Bernard Yvon Jack Vacher, Michael Thomas Withnall
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:
February 9, 1995
Date of Patent:
August 18, 1998
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Alfred P. Spada, Michael R. Myers, Martin P. Maguire, Paul E. Persons
Abstract: The invention is directed to a non-hygroscopic stable crystalline form of the antithrombotic compound N-?N-?N-(4-piperdin-4-yl)butanoyl)-N-ethylglycyl!-(L)-aspartyl!-(L)-.beta. -cyclohexyl-alanine amide, to processes for preparing said stable crystalline form, to a pharmaceutical composition thereof, and intermediates thereof, and the invention is directed also to processes for preparing a compound of the formula ##STR1## wherein: A, B, Z, E.sup.1, E.sup.2, G, R, m, n, and p are as defined herein.
Type:
Grant
Filed:
August 21, 1996
Date of Patent:
July 14, 1998
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Scott I. Klein, Bruce F. Molino, Mark Czekaj, Charles J. Gardner
Abstract: The invention relates to a process for the preparation of intermediates useful in the preparation of (1R,2R)-2-(3-pyridyl)-N-alkyltetrahydro-2H-thiopyran-2-carbothioamide 1-oxides, which possess useful pharmaceutical properties, for example antihypertensive properties, and to intermediates and pharmaceutical products prepared using said process.
Type:
Grant
Filed:
January 5, 1996
Date of Patent:
July 14, 1998
Assignee:
Rhone-Poulenc Rorer Limited
Inventors:
Philippe Pitchen, David Michael Thompson
Abstract: Novel farnesyl transferase inhibitors of general formula (I) ##STR1## preparation thereof and pharmaceutical compositions containing same. In general formula (I), R.sub.1 is Y--S--A.sub.1 -- (where Y is a hydrogen atom, an amino acid residue, a fatty acid residue, or an alkyl or alkoxycarbonyl radical, and A.sub.1 is a C.sub.1-4 alkylene radical optionally .alpha.-substituted in the >C(X.sub.1) (Y.sub.1,) grouping by an amino, alkylamino, alkanoylamino or alkoxycarbonylamino radical wherein the alkyl or alkanoyl portion contains 1-6 carbon atoms; each of X.sub.1 and Y.sub.1 is a hydrogen atom or X.sub.1 and Y.sub.1, taken toether with the carbon atom to which they are attached, form a >C.dbd.O grouping; R'.sub.1 is hydrogen or a C.sub.1-6 alkyl radical; X is an oxygen or sulphur atom; R.sub.2 is a C.sub.1-6 alkyl, alkenyl or alkynyl radical optionally substituted by hydroxy, alkoxy, mercapto, alkylthio, alkylsulphinyl or alkylsulphonyl.
Type:
Grant
Filed:
July 15, 1997
Date of Patent:
May 12, 1998
Assignee:
Phone-Poulenc Rorer SA.
Inventors:
Bernard Baudoin, Christopher Burns, Alain Commercon, Alain Le Brun
Abstract: The invention is directed to a novel compound of formula ##STR1## in which R is a hydroxyl, alkyloxy, phenylalkyloxy or --NH--CH.sub.2 --COOH radical, R' and R" are identical and are each a hydroxy or methoxy radical and R'" represents a hydrogen, bromine, chlorine or iodine atom or a nitro radical. The invention is also directed to the salts of said compounds and their use.
Type:
Grant
Filed:
November 19, 1996
Date of Patent:
May 5, 1998
Assignee:
Rhone-Poulenc Rorer S.A.
Inventors:
Jean-Jacques Debernard, Catherine Dubertret, Gerard Helynck, Jean Leboul, Jean-Paul Martin
Abstract: Compounds of the Formula ##STR1## wherein: K is N or N.fwdarw.O; Q is CH.sub.2 or O; T is ##STR2## or R.sub.3 O--CH.sub.2 ; X is a straight or branched chain alkylene, cycloalkylene or cycloalkenylene group, each of which is optionally substituted by at least one CH.sub.3, CH.sub.3 CH.sub.2, Cl, F, CF.sub.3 or CH.sub.3 O; Y is NR.sub.4, O or S; a=0 or 1; Z is of the formula ##STR3## Z.sub.1 is N, CR.sub.5, (CH).sub.m --CR.sub.5 or (CH).sub.m --N, m being 1 or 2; Z.sub.2 is N, NR.sub.6, O or S, n being 0 or 1; R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are independently H, alkyl, aryl or heterocyclyl; R.sub.a and R.sub.
Type:
Grant
Filed:
May 31, 1995
Date of Patent:
April 7, 1998
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Alfred P. Spada, Cynthia A. Fink, Michael R. Myers
Abstract: A Steptomyces No. CBS 154.94 strain, mutants or derivatives thereof, and a method for preparing peptides using said strain, are disclosed. Novel peptides of general formula (1), pharmaceutical compositions containing same, and the use thereof in cancer therapy, are also disclosed.
Type:
Grant
Filed:
September 27, 1996
Date of Patent:
March 31, 1998
Assignee:
Rhone-Poulenc Rorer S.A.
Inventors:
Jean-Jacques Debernard, Thierry Flamant, Didier Van Der Pyl
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 specifically, they are inhibitors of the activity of Factor Xa. 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, physiological condition which can be ameliorated by the administration of an inhibitor of the activity of Factor Xa.
Type:
Grant
Filed:
December 6, 1996
Date of Patent:
March 24, 1998
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
William R. Ewing, Michael R. Becker, Yong Mi Choi-Sledeski, Heinz W. Pauls, Daniel G. McGarry, Roderick S. Davis, Alfred P. Spada