Rottapharm Spa

Rottapharm Biotech S.r.l.

Rotta Research Laboratorium

Rotta Research Laboratories S.p.a.

Madaus Gmbh

Euromed S.a.

Rottapharm S.r.l.

Rottapharm Bv

Rotta Research Laboraturium S.p.a.

Lucio C Rovati

Francesco Makovec

Antonio Giordani

Gianfranco Caselli

Roberto Artusi

Luigi A Rovati

Simona Zanzola

Stefano Mandelli

Luigi Piero Stasi

Walter Peris

Maurizio Anzini

Andrea Cappelli

Ilario Verpilio

Fabrizio Colace

Tiziana Piepoli

Massimo Maria D'Amato

Sabrina Pucci

Salvatore Vomero

Francesca Tarchino

Silvio Mazzari

Filippo Magaraci

Benedetta Buzzi

Manuela Borriello

Paolo Senin

Gunter Cordes

Mariangela Biava

Michela Visintin

Matteo Ghirri

Antonino Santoro

Laura Mennuni

Ulrich Mengs

Ralf-Torsten Pohl

Marco Lanza

Clara Bovino

Rolando Chiste'

Francesca Porta

Teresa Simonetta Fiorentino

Paola Gilotta

Gabriele Ugolini

Antonio Varnavas

Lucia Lassiani

Vincenzo Calderone

Daniele Maggioni

Lorenzo Perugini

Albino Bonazzi

Wilfried Fischer

Riccardo Chiusaroli

Astrid Nagell

Peter Ferenci

Aguirre Jaime Xiol

Prous Santiago Rull

Emanuele Sala

The invention relates to a N-phenylcarbamoyl compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the inhibition of at least one of tyrosine kinase selected from Fyn and VEGFR2 in the treatment of diseases and disorders involved with one or both kinases.

FYN and VEGFR2 kinase inhibitors

There is described a compound of formula (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)-cyclopropyl)benzoic acid or a pharmaceutically acceptable salt thereof or the form A of its sodium salt for use in the prevention of heterotopic ossification. Preferably such a compound is effective in a specific dose range.

(R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)-cyclopropyl) benzoic acid or its salt also in polymorphic form a for use in the prevention of heterotopic ossification

The present invention provides a process for preparing (R)-6-(tert-butoxycarbonyl)-6-azaspiro[2.5]octane-5-carboxylic acid (SM1), said process comprising the step of: iv) converting a compound of formula (VII) into a compound of formula (VIII) using a Wittig reagent in a suitable solvent; v) reacting through the Makosza reaction the compound of Formula (VIII) using bromoform and a suitable base to obtain cyclopropane compound of Formula (IX); and vi) removing bromine atoms in the presence of a reducing agent and a base in an alcoholic solvent thus obtaining (SM1). The invention relates also to a process for the conversion of the compound (SM1) for preparing (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl) benzoic acid (IV) or a salt thereof. The salt is preferably the sodium salt, more preferably the polymorphic form A of sodium (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)-cyclopropyl) benzoate characterized by a powder XRD spectrum with peaks at values of the angle 2θ+0.2° of 4.3, 5.0, 5.8, 6.4, 7.1, 8.3, 8.7, 12.8, 15.3, 15.9.

Process for the preparation of (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)-cyclopropyl) benzoic acid or a salt thereof

The following invention relates to (R)-4-(1-(1-(4-(trifluoromethyl)benzyl) pyrrodiline-2-carboxamide) cyclopropyl benzoic acid (Compound 1) or a salt thereof. Advantageous methods for obtaining the Compound 1 are also described, as well as pharmaceutical compositions containing it (R)-4-(1-(1-(4-(trifluoromethyl)benzyl)pyrrodiline-2-carboxamide) cyclopropyl benzoic acid (Compound 1) or a pharmaceutically acceptable salt thereof is described for use as an EP4 receptor antagonist in the treatment of a pathology that involves the activities of prostaglandin E(PGE) in its pathogenesis.

(R)-4-(1-(1-(4-(trifluoromethyl)benzyl)pyrrolidine-2-carboxamide)cyclopropyl)-benzoic acid as EP4 receptor antagonist

The present invention provides a pharmaceutical combination comprising the EP4 antagonist of Formula (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl)-benzoic acid or a pharmaceutically acceptable salt thereof and at least one immune checkpoint inhibitor, preferably the sodium salt of (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl) benzoic acid. A polymorphic form A of sodium salt of (R)-4-(1-(6-(4-(trifluoromethyl) benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl)benzoate characterized by a powder XRD spectrum with peaks at values of the angle 2&#x3b8;+0.2&#xb0; of 4.3, 5.0, 5.8, 6.4, 7.1, 8.3, 8.7, 12.8, 15.3, 15.9 is also described. The combination and the polymorphic form A are described for use in the treatment of tumours.

Pharmaceutical combination of an EP4 antagonist and immune checkpoint inhibitors for the treatment of tumours

The invention relates to new selective FYN kinase inhibitors of Formula (I), pharmaceutical compositions containing them, and their use for the pharmacological treatment of pain and arthritis, including osteoarthritis and rheumatoid arthritis.

FYN kinase inhibitors

The present invention relates to an antibody, recombinant or synthetic antigen-binding fragments thereof able to recognize and bind an epitope comprised in the spacer domain of ADAMTS-5, nucleic acid and expression vector encoding the same, method of production and uses thereof.

Anti-ADAMTS-5 antibody, derivatives and uses thereof

The invention concerns a spiro-amino compound of Formula (I), wherein A is selected from a 5- or 6-membered aromatic ring and a 5- or 6-membered heteroaromatic ring containing 1 to 3 nitrogen atom; X is a substituent selected from the group consisting of (C-C)alkyl and halogen, Y is a substituent selected from the group consisting of halogen and trifluoromethyl or a pharmaceutically acceptable salt thereof for use in the treatment of pathologies which require an antagonist of the NK1 receptor. 

Spiro aminic compounds with NK1 antagonist activity

The invention, in a first aspect relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein

4,4-difluoro-piperidine-compounds

The present invention relates to an antibody, recombinant or synthetic antigen-binding fragments thereof able to recognize and bind an epitope comprised in the TrkA amino acid sequence, medical uses thereof and a pharmaceutical composition comprising at least one of the above antibody, recombinant or synthetic antigen-binding fragments thereof.

Anti-TrkA antibodies, derivatives and uses thereof

The invention relates to the use of a silibinin component for the production of a medicament that is adapted for parenteral administration for the treatment of viral hepatitis, preferably of hepatitis B or C, in particular for the reduction of the virus load. The medicament preferably contains no silidianin and/or no silichristin and/or no isosilibinin.

Silibinin component for the treatment of hepatitis

There is described a novel group of cyclic amine derivative compounds, having an EPreceptor antagonistic activity and specifically pharmaceutical compounds which are useful for the treatment or alleviation of Prostaglandin E mediated diseases. The present invention therefore relates to novel compounds which are selective antagonists of the EPsubtype of PGEreceptors with analgesic and antinflammatory activity, processes for their preparation, pharmaceutical compositions containing them and their use as medicaments, inter alia for the treatment or alleviation of Prostaglandin E mediated diseases such as acute and chronic pain, osteoarthritis, inflammation-associated disorder as arthritis, rheumatoid arthritis, cancer, migraine and endometriosis.

[object Object]

The present invention provides compounds of formula (I) including stereoisomers or a racemate or a mixture or a pharmaceutically acceptable salt thereof: wherein X is NH, or O; Q is 5-6 membered heteroaryl group, which may be substituted by one or more substituents independently selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; A is phenyl or a 5-6 heteroaryl group, which may be substituted by one or more substituents independently selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; B may assume different meanings from A and is phenyl or a 5-6 membered heteroaryl group, which may be substituted by one or more substituents independently selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; and processes for their preparation, pharmaceutical compositions containing them and their use as dual antagonists of the Orexin 1 and Orexin 2 receptors. 

2-azabicyclo[4.1.0]heptane derivatives as orexin receptor antagonists for the treatment of certain disorders

The present invention relates to the solid state of 6-(1H-imidazol-1-yl)-2-phenylquinazoline (I) and therefore to novel crystalline forms of the base and of pharmaceutically acceptable salts and solvates thereof, and also to methods for preparing them, to the respective pharmaceutical formulations and to their therapeutic use.  Compound (I) may be obtained as the free base in five different crystalline forms, three polymorphic forms and two hydrates. Some pharmaceutically acceptable salts of (I) that have physicochemical characteristics acceptable for pharmaceutical development were obtained, and the respective polymorphic forms and/or hydrates were characterized.

Crystalline forms of 6-(1H-imidazol-1-yl)-2-phenylquinazoline

1,5-diaryl-2-alkylpyrrole-3-substituted nitro esters, of Formula (I) are provided. Such compounds are potent and selective COX-2 inhibitors which are able to release NO in concentrations that make it possible to counteract the side effects due to selective COX-2 inhibition, without giving rise to hypotensive effects. Formula (I) includes compounds wherein the groups R' and R&#x2033; are: &#x2014;H, &#x2014;F, &#x2014;Cl, &#x2014;Br, &#x2014;CH, &#x2014;CF, &#x2014;OCH, &#x2014;SCH, R1 is methyl, ethyl, trifluoromethyl, hydroxymethyl, methoxymethyl and the substituent in position &#x2212;3 of the pyrrole ring is a chain, where the groups X, Y, Z, W and R2 are: X is a carbonyl or a group &#x2014;(CHR)&#x2014;, Y is an oxygen atom or the group &#x2014;NR&#x2014; and Z is a carbonyl or a group &#x2014;(CHR)&#x2014;, or a [&#x2014;CH(COOH)&#x2014;] group, or a group &#x2014;(NR)&#x2014;, W is an aliphatic chain substituted with one or two (&#x2014;O&#x2014;NO) groups, R2 is: &#x2014;H, &#x2014;OH, &#x2014;OCH, or &#x2014;NHR. Ris: &#x2014;H, &#x2014;CH, &#x2014;CHCH, [&#x2014;CH(CH)]. R&#x2032;&#x2033; is methylsulphonyl or sulphonamido. Pharmaceutical formulations and methods of making an using such formulations are also provided.

1,5-Diary1-2-alkylpyrrole-3-substituted nitro esters, selective COX-2 inhibitors and nitric oxide donors

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Monza, Italy

Lucio C Rovati