Abstract: A compound of formula (I) ##STR1## wherein R' is hydrogen or methyl, m is zero or 1 and the symbol means that the azabicyclic rings may be in the .alpha. or the .beta. orientation, and the pharmaceutically acceptable salts thereof, are useful in treating CNS disorders, gut motility disorders, and/or emesis and/or pain in mammals, and/or migraine.
Type:
Grant
Filed:
November 30, 1992
Date of Patent:
November 8, 1994
Assignee:
Farmitalia Carlo Erba S.r.l.
Inventors:
Angelo Bedeschi, Walter Cabri, Ilaria Candiani, Silvia De Bernardinis, Marcello Marchi, Mario Varasi
Abstract: A process for preparing penem esters by reacting ##STR1## wherein R.sub.1 is a hydroxy protecting group and X is a C.sub.1 -C.sub.10 alkyl or aryl group, with ##STR2## wherein R.sub.2 is hydrogen or a C.sub.1 -C.sub.6 alkyl group in the presence of an anhydrous organic solvent, condensing the product with ##STR3## wherein X is a halogen atom or a --OCOOR.sub.3 group and then cyclizing.
Type:
Grant
Filed:
September 21, 1992
Date of Patent:
November 1, 1994
Assignee:
Farmitalia Carlo Erba S r l
Inventors:
Angelo Bedeschi, Walter Cabri, Marcello Marchi, Ettore Perrone
Abstract: There are provided compounds I ##STR1## wherein A is a hydrogen atom or an organic group,R.sub.1 is hydrogen or halogen atom or an organic group,R.sub.2 is hydrogen or halogen atom, C.sub.1 -C.sub.4 alkyl or acyloxy group,R.sub.3 is hydrogen atom, C.sub.1 -C.sub.4 alkyl or alkoxy, benzyl group or a methylene andR.sub.4 is chloro, fluoro, hydrogen atom or an organic group.The compounds I are elastase inhibitors. A process for their preparation is also provided, as are pharmaceutical compositions containing them.
Type:
Grant
Filed:
October 22, 1991
Date of Patent:
October 18, 1994
Assignee:
Farmitalia Carlo Erba
Inventors:
Marco Alpegiani, Pierluigi Bissolino, Ettore Perrone, Francesco Di Matteo, Piergiuseppe Orezzi, Giuseppe Cassinelli
Abstract: The present invention relates to anti-thrombin polypeptides isolated from the leech Hirudinaria manillensis and to processes for their preparation.The polypeptides of the invention may be modified by way of amino acid extension at either or each end, and may be subjected to post-translational modification.The anti-thrombin polypeptides may be prepared by isolating them from the tissue or secretions of the leech Hirudinaria manillensis but they also may be synthetized by recombinant DNA methods.According to this latter aspect, the invention provides DNA sequences, expression vectors and host cell lines for the recombinant preparation of the polypeptides.The anti-thrombin polypeptides of the invention find an useful application in the treatment of venous thrombosis, vascular shunt occlusion and thrombin-induced disseminated intravascular coagulation.
Type:
Grant
Filed:
February 26, 1992
Date of Patent:
October 18, 1994
Assignee:
Farmitalia Carlo ERBA S.r.l.
Inventors:
Paolo Sarmientos, Philippe de Taxis du Poet, Giampaolo Nitti, Emanuela Scacheri
Abstract: Compounds having formula (I) ##STR1## wherein Z is --O-- or --CH.sub.2 --; n is 1-6; R is hydrogen, C.sub.1 -C.sub.6 alkyl, phenyl or optionally substituted phenyl-C.sub.1 -C.sub.3 alkyl; R.sub.2 is C.sub.1 -C.sub.8 -alkyl, aryl-C.sub.1 -C.sub.3 alkyl, C.sub.5 -C.sub.8 cycloalkyl or C.sub.5 -C.sub.8 cycloalkyl-C.sub.1 -C.sub.3 alkyl; each of R.sub.3 and R.sub.4 independently is hydrogen or C.sub.1 -C.sub.4 alkyl, or taken together with the carbon atom to which they are linked form a C.sub.3 -C.sub.6 cycloalkyl ring; Q is --OR' or --NR'R" in which R' and R" are as herein defined, or Q is C.sub.1 -C.sub.8 alkyl, phenyl, phenyl-C.sub.1 -C.sub.3 -alkyl, C.sub.5 -C.sub.8 cycloalkyl or C.sub.5 -C.sub.8 cycloalkyl-C.sub.1 -C.sub.3 alkyl, in which both the phenyl and cycloalkyl rings or moieties are optionally substituted as herein defined; and the pharmaceutically acceptable salts thereof; are useful in particular as antidislipidaemic and antiatherosclerotic agents.
Type:
Grant
Filed:
July 24, 1992
Date of Patent:
October 18, 1994
Assignee:
Farmitalia Carlo Erba SRL.
Inventors:
Paolo Cozzi, Daniele Fancelli, Severino Dino, Augusto Chiari, Giancarlo Ghiselli
Abstract: This invention relates to a method of treating rheumatoid arthritis, which method comprises administering to a mammal a therapeutically effective amount of a compound of formula (I): ##STR1## wherein R1 is unsubstituted or substituted phenyl;R.sub.2 is a morpholinomethyl group;R.sub.3 is hydrogen;R.sub.4 is hydrogen or C.sub.1 -C.sub.6 alkyl;R.sub.a is hydrogen; andR.sub.b is a group --(A).sub.m --R.sub.5 wherein m is zero or 1, A is a C.sub.1 -C.sub.6 alkylene chain and R.sub.5 is unsubstituted or substituted phenyl;or a pharmaceutically acceptable salt thereof.
Type:
Grant
Filed:
July 1, 1993
Date of Patent:
October 4, 1994
Assignee:
Farmitalia Carlo Erba Srl
Inventors:
Gianfederico Doria, Anna M. Isetta, Rinaldo Ferreccio, Mario Ferrari, Maria C. Fornasiero, Domenico Trizio
Abstract: The present invention relates to the production, by recombinant DNA techniques, of derivatives of basic fibroblast growth factor (bFGF). These derivatives of bFGF can act as antagonists and/or superagonists of the wild type molecule in the angiogenic process. These derivatives, as well as wild type bFGF, may be prepared by the use of strains or E. coli which have been transformed with plasmids carrying nucleotide sequence coding for human and bovine bFGF and their derivatives.
Type:
Grant
Filed:
June 2, 1993
Date of Patent:
October 4, 1994
Assignee:
Farmitalia Carlo Erba S.R.L.
Inventors:
Laura Bergonzoni, Antonella Isacchi, Paolo Sarmientos, Gilles Cauet
Abstract: A bFGF is prepared by:(i) forming an adduct between heparin or heparan sulphate and a bFGF which has the 9-10 Leu-Pro bond;(ii) treating the adduct with pepsin A or cathepsin D, thereby cleaving the said bond; and(iii) releasing from the adduct the bFGF thus obtained.This process may be applied to prepare the 146 amino acid form of bFGF from longer forms of bFGF. It may also be used to produce a single form of bFGF from a mixture of bFGFs whose amino acid sequences differ only by having different N-terminii.
Type:
Grant
Filed:
April 2, 1992
Date of Patent:
September 20, 1994
Assignee:
Farmitalia Carlo Erba S.R.L.
Inventors:
Pierre Monsan, Francois Paul, Didier Betbeder, Paolo Sarmientos
Abstract: Cephalosporins of the formula (I): ##STR1## wherein m is one or two; n is zero, one or two; A and B are organic residues; and R.sub.1 and R.sub.2 are halogen or hydrogen atoms or organic groups are endowed with elastase inhibitory activity. Two processes for their preparation starting from the corresponding 4-acyl cephem are also provided.
Type:
Grant
Filed:
June 12, 1992
Date of Patent:
September 20, 1994
Assignee:
Farmitalia Carlo Erba S.R.L.
Inventors:
Pierluigi Bissolino, Marco Alpegiani, Ettore Perrone, Piergiuseppe Orezzi, Giuseppe Cassinelli, Giovanni Franceschi
Abstract: The preparation of a compound of formula (I) ##STR1## wherein X is oxygen or sulphur; R.sub.1 is hydrogen or C.sub.1 -C.sub.6 alkyl; each of R.sub.2 and R.sub.3 is, independently, hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.5 or C.sub.6 cycloalkyl or C.sub.6 -C.sub.9 cycloalkylalkyl; R.sub.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 - or C.sub.6 cycloalkyl, C.sub.6 -C.sub.9 cycloalkylalkyl or aryl; and the symbol represents a single or a double bond; by a multi-step process is disclosed.
Type:
Grant
Filed:
March 19, 1993
Date of Patent:
August 30, 1994
Assignee:
Farmitalia Carlo Erba S.R.L.
Inventors:
Achille Panzeri, Lucio Ceriani, Pierluigi Griggi, Marcella Nesi
Abstract: The present invention relates to 3-deoxy-derivatives of D-mannosamine of formula ##STR1## wherein R is --NH.sub.2 or a C.sub.2 -.sub.5 alkanoyl-NH-- or CF.sub.3 CONH-- group; each of R.sub.1 and R.sub.2 independently is C.sub.1 -C.sub.4 alkyl, or R.sub.1 is hydrogen, halogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy, and R.sub.2 is hydrogen or both of R.sub.1 and R.sub.2 are fluorine; and wherein, when R.sub.1 is methoxy and R.sub.2 is hydrogen then R is other than --NH.sub.2, or a pharmaceutically acceptable salt thereof, which are useful as angiogenesis inhibitors, in particular as development of metastasis inhibitors.
Type:
Grant
Filed:
July 31, 1992
Date of Patent:
July 26, 1994
Assignee:
Farmitalia Carlo Erba S.R.L.
Inventors:
Nicola Mongelli, Alberto Bargiotti, Nuccia Oneto, Cristina Geroni
Abstract: The invention relates to distamycin A analogs of the following formula ##STR1## wherein n is 2, 3 or 4; A is an optionally substituted divalent radical chosen from ##STR2## and --Het-- wherein Het is a pentatomic or hexatomic heteromonocyclic ring, except pyrrole; and wherein either one of R.sub.1 and R.sub.2 is hydrogen and the other is an acylating moiety or R.sub.1 and R.sub.2 are both hydrogen or both alkyl groups optionally substituted, including the pharmaceutically acceptable salts of the said compounds.The compounds of the invention can be useful antitumor and antiviral agents.
Type:
Grant
Filed:
August 10, 1992
Date of Patent:
May 10, 1994
Assignee:
Farmitalia Carlo Erba SpA
Inventors:
Ettore Lazzari, Federico Arcamone, Sergio Penco, Maria A. Verini, Nicola Mongelli
Abstract: Morpholinyl derivatives of doxorubicin having the general formula A: ##STR1## in which X represents a linear or branched C.sub.2 -C.sub.6 alkyl group or a benzyl group --CH.sub.2 C.sub.6 H.sub.5 and which have (S) or (R) configuration at carbon atom C-2" of the morpholino ring, are antitumor agents.
Type:
Grant
Filed:
January 13, 1993
Date of Patent:
April 19, 1994
Assignee:
Farmitalia Carlo Erba S.R.L.
Inventors:
Alberto Bargiotti, Maria Grandi, Antonino Suarato, Daniela Faiardi
Abstract: The present invention relates to a process for the preparation of exomethylene cephams, which are useful intermediates in the production of many useful .beta.-lactam antibiotics.More particularly there is provided a process for preparing a compound of formula I ##STR1## wherein n is O or 1, R.sub.1 is hydrogen atom or an organic residue and R.sub.2 is a carboxy protecting group, which process comprises reacting a compound of the formula II ##STR2## wherein X is halogen atom or acetoxy group and R.sub.1 n and R.sub.2 are as defined above with a lanthanide complex.
Type:
Grant
Filed:
February 16, 1993
Date of Patent:
April 19, 1994
Assignee:
Farmitalia Carlo Erba S.r.l.
Inventors:
Walter Cabri, Ilaria Candiani, Angelo Bedeschi
Abstract: A crystalline form of (5R,6S)-2-carbamoyloxymethyl-6-[(1R)-hydroxyethyl]-2-penem-3-carboxylic acid incorporates two molecules of water per molecule of the acid and is useful as an antibacterial agent.
Type:
Grant
Filed:
June 16, 1992
Date of Patent:
April 12, 1994
Assignee:
Farmitalia Carlo Erba
Inventors:
Carlo Battistini, Roberto Bianchini, Stefano del Nero, Pierluigi Griggi, Sergio Vioglio
Abstract: The present invention provides a polypeptide which is capable of binding specifically human basic fibroblast growth factor and human acidic fibroblast growth factor, a DNA sequence which encodes the polypeptide of the invention and a vector which incorporates a DNA sequence of the invention and which is capable, when provided in a transformed host, of expressing the polypeptide of the invention encoded by the DNA sequence. A host transformed with such a vector forms part of the invention also.
Type:
Grant
Filed:
December 28, 1992
Date of Patent:
February 22, 1994
Assignee:
Farmitalia Carlo Erba
Inventors:
Laura Bergonzoni, Guy Mazue, Antonella Isacchi, Romeo Roncucci, Paolo Sarmientos
Abstract: A pharmaceutcial composition is provided for use in the prevention or treatment of viral infections caused by enveloped viruses. The composition comprises a fibroblast growth factor, a sulfated polysaccharide with antiviral activity, and one or more pharmaceutically acceptable carriers. The fibroblast growth factor may be a basic fibroblast growth factor or an analogue thereof, and the polysaccharide may be a carrageenan, heparin, dextran sulfate, pentosan polysulfate or a sulfated polysaccharides produced by marine algae belonging to the class of Rhodophyceae.
Type:
Grant
Filed:
January 31, 1992
Date of Patent:
February 22, 1994
Assignee:
Farmitalia Carlo Erba S.R.L.
Inventors:
Domenico Ungheri, Luisa Garofano, Carlo Battistini, Paolo Carminati, Guy Mazue
Abstract: The present invention relates to a novel process for preparing uracil derivatives useful as intermediates in the synthesis of uridines having antiviral or antitumor activity or useful as coadjuvants in antiviral therapy, characterized by converting a compound of the formula II into its mesylate derivative of the formula III which is the reduced to give the desired compound of the formula I: ##STR1## in which R.sub.1 is H, halogen, alkyl, aryl or aralkyl.
Type:
Grant
Filed:
August 21, 1992
Date of Patent:
February 15, 1994
Assignee:
Farmitalia Carlo Erba S.r.l.
Inventors:
Angelo Bedeschi, Walter Cabri, Ilaria Candiani, Tiziano Martinengo
Abstract: The present invention relates to 2-(imidazol-1-yl)-2 -benzylethylidene-aminoxyalkanoic acid derivatives of formula (I) ##STR1## wherein A is a divalent group of formula ##STR2## in which R is hydrogen, halogen, CF.sub.3, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylsulfonyl or cyano;R.sub.1 is a) phenyl unsubstituted or substituted by halogen, C.sub.1 -C.sub.4 alkoxy, CF.sub.3 or C.sub.1 -C.sub.4 alkylsulfonyl; b) cyclohexyl; or c) a straight or branched C.sub.1 -C.sub.6 alkyl group;T is a branched or straight C.sub.3 -C.sub.5 alkylene chain;R.sub.2 is hydrogen or C.sub.1 -C.sub.4 alkyl, and the pharmaceutically acceptable salts thereof, which are useful as selective inhibitors of thromboxane A.sub.2 (TxA.sub.2) synthesis.
Type:
Grant
Filed:
July 22, 1992
Date of Patent:
February 1, 1994
Assignee:
Farmitalia Carlo Erba S.r.l.
Inventors:
Paolo Cozzi, Maria Menichincheri, Arsenia Rossi, Corrado Ferti, Patricia Salvati
Abstract: 1-(Alkoxy-iminoalkyl)imidazole derivatives of formula ##STR1## wherein R is hydrogen or C.sub.1 -C.sub.4 alkyl; A is C.sub.1 -C.sub.4 alkylene optionally substituted by phenyl optionally substituted by halogen or trifluoromethyl; R is (a) hydrogen or a C.sub.1 -C.sub.10 hydrocarbon radical; (b) an aryl or aryl-C.sub.1 -C.sub.4 alkyl group wherein the said aryl is optionally substituted either by halogen, trihalo-methyl, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.3 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio or C.sub.1 -C.sub.4 alkylsulfonyl or by C.sub.5 -C.sub.8 alkyl, C.sub.4 -C.sub.8 alkenyl, C.sub.5 -C.sub.8 alkoxy, C.sub.5 -C.sub.8 alkylthio or phenyl optionally substituted by halogen, trihalomethyl or C.sub.1 -C.sub.4 alkyl; or (c) a C.sub.5 -C.sub.8 cycloalkyl or C.sub.5 -C.sub.8 cycloalkyl-C.sub.1 -C.sub.4 alkyl group, wherein the said cycloalkyl is optionally substituted by C.sub.1 -C.sub.4 alkyl; T is a C.sub.1 -C.sub.