Janssen Pharmaceutica Nv

Other

Frederik Dirk Deroose

Eddy Jean Edgard Freyne

Jean Fernand Armand Lacrampe

Davy Petrus Franciscus Maria Petit

Maria Encarnacion Matesanz-Ballesteros

Rosa Maria Alvarez Escobar

Marc Gaston Venet

José Ignacio Andrés-Gil

Werner Constant Johan Embrechts

Jérôme Michel Claude Fortin

Erwin Coesemans

Jos&eacute; Ignacio Andr&eacute;s-Gil

Yannick Ligny

The present invention is concerned with the compounds of formula wherein m, n and p are each independently 0 or 1 and q is 0, 1, 2, 3, 4 or 5; -A=A-A=A- is a pyridinylidene, pyridazinylidene, pyrimidinylidene, pyrazinylidene or phenylidene; B represents an amide, ketone or oxadiazole; D represents Ar or Het; Q represents a covalent direct bond or a ketone, &#x2014;N&#x2014;, &#x2014;O&#x2014;, &#x2014;CRR&#x2014;, amide, ethenyl, imine, sulfonyl, sulfinyl, 3-oxobutenyl, pyrazole, isoxazole or thiazole; L represents Ar or Het; Rrepresents hydrogen, halo, hydroxy, Calkenyl, Calkynyl, Ccycloalkyl, Ccycloalkenyl, cyano, guanidine, nitro, NRR, an optionally substituted Calkyl or Calkyloxy; Rand Reach independently represent hydrogen, halo, Calkyloxy or an optionally substituted Calkyl; Rand Reach independently represent hydrogen, hydroxy, halo, an optionally substituted Calkyl, Calkenyl, Calkynyl, Ccycloalkyl, Ccycloalkenyl, Calkyloxy, cyano, (C&#x2550;O)R, (C&#x2014;O)OR, (SO)R, aminocarbonyloxy, aminoCalkyl, NRR, N, Ar or Het; or Rand Rtogether with the carbon atom to which they are attached, form an Ar or Het; Ar represents an optionally substituted Caryl; Het represents an optionally substituted Cheterocycle; or a N-oxide, pharmaceutically acceptable addition salt, quaternary amine or stereochemically isomeric form thereof; the processes for their preparation and compositions comprising them. It further relates to their use as a medicine.

4,5-dihydro-isoxazole derivatives and their pharmaceutical use

The present invention relates to IL-5 inhibiting 6-azauracil derivatives useful for treating eosinophil-dependent inflammatory diseases, to processes and intermediates for their preparation as well as to pharmaceutical compositions comprising the said derivatives. It further relates to the use of such derivatives as a medicine, and to processes for marking a receptor or imaging an organ using the said derivatives.

Non-steroidal IL-5 inhibitors, processes and intermediates for their preparation and pharmaceutical compositions comprising said inhibitors

The present invention is concerned with the compounds of formulathe N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein p is 0 to 4; X is O, S, NRor a direct bond; Y is O, S, NRor S(O); Rindependently is Calkyl, halo, polyhaloCalkyl, hydroxy, mercapto, Calkyloxy, Calkylthio, Calkylcarbonyloxy, aryl, cyano, nitro, Het, R, NRRor substituted Calkyl; Ris Het, Ccycloalkyl or optionally substituted Calkyl and if X is O, S or NR, then Rmay also represent aminocarbonyl, aminothiocarbonyl, Calkylcarbonyl, Calkylthiocarbonyl, arylcarbonyl, arylthiocarbonyl, Hetcarbonyl or Hetthiocarbonyl; Rand Rindependently are hydrogen, Calkyl or Ccycloalkyl; Rand Rform a Calkanediyl; Ris hydrogen or Calkyl; Ris a sulfonyl or sulfinyl derivative; Rand Rare independently hydrogen, optionally substituted Calkyl, aryl, a carbonyl containing moiety, Ccycloalkyl, &#x2014;Y&#x2014;Calkanediyl-C(&#x2550;O)&#x2014;O&#x2014;R, Het, Hetand R; Ris hydroxy, mercapto, cyano, nitro, halo, trihalomethyl, Calkyloxy, formyl, trihaloCalkylsulfonyloxy, R, NRR, C(&#x2550;O)NRR, Calkanediyl-C(&#x2550;O)&#x2014;O&#x2014;R, &#x2014;C(&#x2550;O)&#x2014;O&#x2014;R, &#x2014;Y&#x2014;Calkanediyl-C(&#x2550;O)&#x2014;O&#x2014;R, aryl, aryloxy, arylcarbonyl, Ccycloalkyl, Ccycloalkyloxy, phthalimide--yl, Hetand C(&#x2550;O)Het; Ris hydrogen, Calkyl, Ccycloalkyl, aminocarbonylmethylene or mono- or di(Calkyl)aminocarbonylmethylene; aryl is optionally substituted phenyl; Het, Het, Hetand Hetare optionally substituted heterocycles; to processes for their preparation and compositions comprising them. It further relates to their use as a medicine.

IL-5 inhibiting 6-azauracil derivatives

The present invention is concerned with the compounds of formula (I), a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein p is 0 to 4; q is 0 to 5; X is O, S, NR or a direct bond; or &mdash;X&mdash;R is CN; R is H, OH, halo, NH , mono- or di(C alkyl)NH , C alkyl, C alkylO, C cycloalkyl, aryl, arylC alkyl, NH C akyl, mono- or di(C alkyl)NH C akyl or mono- or di(C alkyl)NH C alkylNH ; R is aryl, Het , optionally substituted C cycloalkyl, optionally substituted C alkyl; R is H or C alkyl; R and R are &mdash;C(&boxH;O)&mdash;Z&mdash;R , C alkyl, halo, polyhaloC alkyl, OH, mercapto, C alkylO, C alkylthio, C alkylC(&boxH;O)O, aryl, cyano, nitro, Het , R , NR R or C alkyl substituted with &mdash;C(&boxH;O)&mdash;Z&mdash;R , Het , R or NR R ; Z is O, S, NH, &mdash;CH O or &mdash;CH &mdash;S&mdash;; R is H, C acyl, optionally substituted C alkyl, optionally substituted C alkenyl, C alkynyl, C cycloalkyl, polyhaloC alkyl, Het , phenyl; or R is an oxygen containing radical; aryl is optionally substituted phenyl; Het , Het , Het and Het are optionally substituted heterocycles; Het is a monocyclic heterocycle; provided however that R is other than NH C(&boxH;O), C alkylOC(&boxH;O)C alkyl; and R is other than COOH, C alkylOC(&boxH;O), NH C(&boxH;O), C alkylNH C(&boxH;O), OHC alkylNH C(&boxH;O), C alkylC(&boxH;O)NH C(&boxH;O), C cycloalkylNH C(&boxH;O); and R , R , R , R , R , R , R and R are other than C alkylC(&boxH;O)OC alkylC(&boxH;O), OHC alkylC(&boxH;O); and Het is other than a monocyclic heterocycle substituted with COOH or C alkylOC(&boxH;O); and the compounds of formula (I) contain at least one &mdash;C(&boxH;O)&mdash;Z&mdash;R moiety: to processes for their preparation and compositions comprising them. It further relates to their use as a medicine.

Il-5 inhibiting 6-azauracil derivatives

Growing community of inventors

Drongen, Belgium

Frederik Dirk Deroose