Rottapharm Biotech S.r.l.

Rottapharm Spa

Rotta Research Laboratorium

Rottapharm S.r.l.

Rotta Research Laboraturium S.p.a.

Roberto Artusi

Lucio C Rovati

Francesco Makovec

Simona Zanzola

Stefano Mandelli

Antonio Giordani

Gianfranco Caselli

Fabrizio Colace

Luigi Piero Stasi

Ilario Verpilio

Tiziana Piepoli

Benedetta Buzzi

Filippo Magaraci

Laura Mennuni

Clara Bovino

Sabrina Pucci

Marco Lanza

Lorenzo Perugini

Lucio Claudio Rovati

Massimo Maria D'amato

Lucio Rovati

Ornella Letari

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

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

4,4-difluoro-piperidine-compounds

The invention relates to a novel compound of formula (I) or a stereoisomer, or a racemate or a mixture or a pharmaceutically acceptable salt thereof: wherein: R is phenyl or a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from S, N and O, such rings may be optionally substituted with n groups Q; Q is selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN, SOCHor a group &#x2014;O[(CRR]pQ; or Q may be a group Q; Qis phenyl, which may be optionally substituted with n substituents selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN, or a group Q; or corresponds to 2,2-difluoro-benzo[d][1,3]dioxol-4-yl; Q2 is a 5- or 6-membered heteroaryl containing at least one nitrogen atom, which may optionally substituted with n substituents selected from a group consisting of: C1 C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; P is a 6-membered heteroaryl or a 8-1 1 membered bicyclic heteroaryl group, which may be substituted with n substituents selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; Ris hydrogen or C1-C3 alkyl; Ris hydrogen or C1-C3 alkyl; n is 1, 2 or 3; p is 0, 1 or 2; and with the proviso that when R corresponds to phenyl, P is substituted by at least one CF; processes for the preparation of those compounds, pharmaceutical compositions containing one or more compounds of formula (I) and their use as dual antagonists of the Orexin 1 and Orexin 2 receptors. 

Chemical compounds

2-aryl and 2-heteroaryl 4h-1-benzopyran-4-one-6-amidino derivatives formula (I) useful as pharmacological agents for the treatment of arthritis, cancer and related pain.

2-aryl and 2-heteroaryl 4H-1-benzopyran-4-one-6-amidino derivatives, new pharmacological agents for the treatment of arthritis, cancer and related pain

Compounds which may be represented by the general formula (I) shown below and in which: Ris a group independently selected from among: CHO, &#x2014;COOH, &#x2014;CHOH Ris hydrogen or a linear or branched C-Calkyl group Ris hydrogen or a halogen group selected from among Cl and Br Ris a linear or branched C-Calkyl group and the pharmaceutically acceptable salts thereof such as the sodium or potassium salt. The compounds exhibit potent and selective All antagonist activity and are useful for the treatment of any disorders in which elevated synthesis of All or overexpression of the ATreceptor may play a primary pathological role, as in the case of arterial hypertension, congestive cardiac insufficiency, platelet aggregation and disorders associated therewith such as for example myocardial and cerebral infarction, renal ischaemia, venous and arterial thrombosis, peripheral vasculopathy, pulmonary hypertension, diabetes mellitus, diabetic neuropathy, glaucoma and diabetic retinopathy. 

Pyrrole derivatives with angiotensin II antagonist activity

Heterocyclic amidines with anti-inflammatory and analgesic activity that inhibit nitrogen oxide production, of formula (I): in which: and in which the substituents W, Y and X are combined to form 9- or 10-membered bicyclic heteroaromatic derivatives containing up to 2 hetero atoms in the same ring; and

Anti-inflammatory and analgesic heterocyclic amidines that inhibit nitrogen oxide (NO) production

Compounds which can be represented by the general formula (I) indicated below: and in which:

Benzamidine derivatives having anti-inflammatory and immunosuppressive activity

The invention describes compounds represented by the general formula (I) given below: in which:

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Rho, Italy

Roberto Artusi