Rottapharm Biotech S.r.l.

Rottapharm S.r.l.

Fabrizio Colace

Lucio C Rovati

Roberto Artusi

Stefano Mandelli

Luigi Piero Stasi

Clara Bovino

Gianfranco Caselli

Tiziana Piepoli

Benedetta Buzzi

Manuela Borriello

Filippo Magaraci

Laura Mennuni

Lorenzo Perugini

Lucio Claudio Rovati

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 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

The invention relates pyridine amide derivative of Formula (I) or a pharmaceutically acceptable salt thereof, wherein Rand Rare independently hydrogen, linear o branched (C1-C3)alkyl or joined together they form a cyclopropyl ring; R is independently selected from the group consisting of halogens and trifluoromethyl and p is 1, 2 or 3; A is C or N; E is a group of formula (B) or (C), wherein B is C(O)OH, C(O)O(C1-C3)alkyl, and C is selected from the group consisting of formula (I) m is 1,2 or 3, n is 0 or 1, W is &#x2014;O&#x2014;, &#x2014;O(C1-C3 alkyl)-; &#x2014;(C1-C3 alkyl)O&#x2014;; &#x2014;C(O)&#x2014;; &#x2014;C(&#x2550;N&#x2014;O(C1-C3 alkyl))-; &#x2014;NH&#x2014; or &#x2014;NH(C1-C3alkyl)-; Ar is phenyl, optionally substituted with one or more substituents selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, methyl, &#x2014;NH(C1-C3alkyl)-; &#x2014;N(C1-C3alkyl)(C1-C3alkyl)-, a from 5 to 7 membered heterocyclic ring containing one nitrogen atom which is covalently bonded to Ar and optionally containing one or two heteroatoms selected from N, O and S; and a 5- or 6-membered heteroaromatic ring containing 1 to 3 heteroatoms selected from S, O e N, such heteroaromatic ring being substituted with one or two substituents selected from the group consisting of (C1-C3)alkyl, (C3-C5)cycloalkyloxy, (C1-C3)alkylcarbonyl. The compounds of the invention could be used for manufacturing a medicament for the treatment of pathologies which require the use of an antagonist of the EP4 receptor, such as the treatment of acute and chronic pain, inflammatory pain, osteoarthritis, inflammation-associated disorder as arthritis, rheumatoid arthritis, cancer, endometriosis and migraine. 

Pyridine amide derivatives as EP4 receptor antagonists

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Monza, Italy

Fabrizio Colace