Rottapharm Spa

Rottapharm Biotech S.r.l.

Rottapharm S.r.l.

Stefano Mandelli

Lucio C Rovati

Antonio Giordani

Francesco Makovec

Simona Zanzola

Gianfranco Caselli

Lucio Claudio Rovati

Roberto Artusi

Ilario Verpilio

Silvio Mazzari

Francesca Tarchino

Luigi Piero Stasi

Tiziana Piepoli

Fabrizio Colace

Matteo Ghirri

Marco Lanza

Benedetta Buzzi

Filippo Magaraci

Teresa Simonetta Fiorentino

Laura Mennuni

Lorenzo Perugini

Francesca Porta

Clara Bovino

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 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

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

The present invention is directed to 6-(1H-imidazo-1-yl)-2-aryl and 2-heteroaryl quinazoline and quinolines derivatives, compounds of formula (I), their pharmaceutical acceptable salts and solvates and corresponding pharmaceutical compositions, that acts as Monoamine Oxidase (MAO) inhibitors and Imidazoline Receptor ligands: wherein: X is independently selected from &#x2014;CH group or a nitrogen atom (&#x2014;N), W is independently selected from an aryl group, an heteroaryl group, or a benzocondensed heteroaryl group such as 1,3-benzodioxole, benzofuran, 2,3-dihydrobenzofuran, benzothiophene, 2,3-dihydrobenzothiophene, indole, 2,3-dihydroindole, benzimidazole, benzoxazole, benzothiazole, 2H-3,4-dihydrobenzopyran, [1,4]-benzodioxine, 2,3-dihydro-[1,4]-benzodioxine (1,4-benzodioxan). Ris independently selected from hydrogen (&#x2014;H), C-Calkyl, hydroxymethyl (&#x2014;CHOH), aminomethyl (&#x2014;CHNH), alkylaminomethyl [CHNH(R)], or di-alkylaminomethyl [CHN(R)], trifluoromethyl (&#x2014;CF). Compounds of formula (I) elicited a pharmacological profile suitable for the clinical treatment of depression and related disorders, Parkinson disease, drug abuse, and morphine tolerance and dependence.

6-1H-imidazo-quinazoline and quinolines derivatives, new MAO inhibitors and imidazoline receptor ligands

The present invention is directed to novel 6-1H-imidazo-2-aryl and 2-heteroaryl quinazoline and quinoline of formula I, corresponding salts and solvates thereof, to a process for their preparation and to the use of this compounds and corresponding pharmaceutical composition for the treatment of pain and inflammatory related disorders. Compounds of the invention have been proven highly effective in the pharmacological treatment of both inflammatory and neuropathic pain, in addition to striking anti-inflammatory properties. Their effectiveness in interfering with COX-2 and inflammatory cytokines expressions and production, highlights them as interesting compounds also for the treatment of cancer in addition to several inflammatory diseases. 

6-1H-imidazo-quinazoline and quinolines derivatives, new potent analgesics and anti-inflammatory agents

The present invention is directed to novel 6-1H-imidazo-2-aryl and 2-heteroaryl quinazoline and quinoline of formula I, corresponding salts and solvates thereof, to a process for their preparation and to the use of this compounds and corresponding pharmaceutical composition for the treatment of pain and inflammatory related disorders. Compounds of the invention have been proven highly effective in the pharmacological treatment of both inflammatory and neuropathic pain, in addition to striking anti-inflammatory properties. Their effectiveness in interfering with COX-2 and inflammatory cytokines expressions and production, highlights them as interesting compounds also for the treatment of cancer in addition to several inflammatory diseases. Formula I: 

The present invention concerns novel amidines derivatives of 2-heteroaryl-quinazoline and quinolines of general formula (I), to a process for their preparation, to their pharmaceutical compositions and to the use of these compounds, salts and solvates thereof, along with the corresponding pharmaceutical compositions, for the treatment of pain and inflammatory disorders. Compounds of this invention are extremely potent analgesics, suitable for the treatment of both inflammatory and neuropathic pain. Particularly for the treatment of neuropathic pain the compounds of the invention have been proved largely superior to the standards currently in the clinical use. These compounds are not acting through inhibition of COX or NOS enzymes but are effective in inhibiting inflammatory cytokine production induced by inflammatory stimuli. 

Amidine derivatives of 2-heteroaryl-quinazolines and quinolines; potent analgesics and anti-inflammatory agents

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

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Casatenovo, Italy

Stefano Mandelli