Rottapharm Biotech S.r.l.

Rottapharm S.r.l.

Fabrizio Colace

Lucio C Rovati

Gianfranco Caselli

Luigi Piero Stasi

Roberto Artusi

Stefano Mandelli

Tiziana Piepoli

Manuela Borriello

Benedetta Buzzi

Filippo Magaraci

Clara Bovino

Lorenzo Perugini

Laura Mennuni

Lucio Claudio Rovati

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