Janssen Pharmaceutica Nv

Other

David William End

Michael J Zelesko

Marc Gaston Venet

Li Liu

Henry Joseph Breslin

Ashis Kumar Saha

Bart Lieven Daniel De Corte

Patrick René Angibaud

Patrick Rene Angibaud

Gerard Charles Sanz

Jean Pierre Frans Van Wauwe

Marina Lucie Louise Cools

Robert Franciscus Van Ginckel

Walter Boudewijin Leopold Wouters

Wim Joanna Floren

(&#x2212;)-5-(3-Chlorophenyl)-&#x3b1;-(4-chlorophenyl)-&#x3b1;-(1-methyl-1H-imidazol-5-yl)tetrazolo-[1,5-a]quinazoline-7-methanamine and its pharmaceutically acceptable acid addition salts, and the use of such compounds in medicine especially for the treatment of cancer.

Farnesyl transferase inhibiting 1,2-annelated quinoline enantiomer

a prodrug, N-oxide, addition salt, quaternary amine or stereochemically isomeric form thereof, wherein Land Lare R&#x2014;Y&#x2014; wherein each (R&#x2014;Y)&#x2014; substituent is defined independently of the other; Y is Calkanediyl, Calkenediyl, Calkynediyl, C(&#x2550;O), or a direct bond; Ris hydrogen, cyano, aryl or a substituted or unsubstituted Cheterocycle; &#x2550;Z&#x2014;Z&#x2550;Z&#x2014; represents a radical of formula &#x2550;N&#x2014;N&#x2550;CH&#x2014; (a-1), &#x2550;N&#x2014;CH&#x2550;N&#x2014; (a-2), &#x2550;CH&#x2014;N&#x2550;N&#x2014; (a-3); X is SO, (CH), wherein n is 1 to 4, C(&#x2550;O), C(&#x2550;S), or a direct bond; Ris aryl, Ccycloalkyl, Ccycloalkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted Cheterocycle, Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl, hydroxyCalkyl, hydroxyCalkyloxy, hydroxyCalkylthio and arylCalkylthio, Calkyl or Calkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted Cheterocycle, Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl, hydroxyCalkyl, hydroxyCalkyloxy, hydroxyCalkylthio and arylCalkylthio; Ris aryl, &#x2014;NRR, a substituted or unsubstituted Cheterocycle, or Calkenediyl substituted with a substituted or unsubstituted Cheterocycle or aryl; Ris hydrogen, aryl, Ccycloalkyl, Calkyl or Calkyl substituted with Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl or aryl; Rand Rare each independently selected from hydrogen, a substituted or unsubstituted Cheterocycle, aryl, Calkyl and Calkyl substituted with one or more substituents selected from hydroxy, aryl, aryloxy or a substituted or unsubstituted Cheterocycle.

Triazoles as farnesyl transferase inhibitors

A prodrug, N-oxide, addition salt, quaternary amine or stereochemically isomeric form thereof, wherein Land Lare R&#x2014;Y&#x2014; wherein each (R&#x2014;Y)&#x2014; substituent is defined independently of the other; Y is Calkanediyl, Calkenediyl, Calkynediyl, C(&#x2550;O), or a direct bond; Ris hydrogen, cyano, aryl or a substituted or unsubstituted Cheterocycle; =Z-Z=Z- represents a radical of formula &#x2550;N&#x2014;N&#x2550;CH&#x2014; (a-1), &#x2550;N&#x2014;CH&#x2550;N&#x2014; (a-2), &#x2550;CH&#x2014;N&#x2550;N&#x2014; (a-3); X is SO, (CH)wherein n is 1 to 4, C(&#x2550;O), C(&#x2550;S), or a direct bond; Ris aryl, Ccycloalkyl, Ccycloalkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted Cheterocycle, Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl, hydroxyCalkyl, hydroxyCalkyloxy, hydroxyCalkylthio and arylCalkylthio, Calkyl or Calkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted Cheterocycle, Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl, hydroxyCalkyl, hydroxyCalkyloxy, hydroxyCalkylthio and arylCalkylthio; Ris aryl, &#x2014;NRR, a substituted or unsubstituted Cheterocycle, or Calkenediyl substituted with a substituted or unsubstituted Cheterocycle or aryl; Ris hydrogen, aryl, Ccycloalkyl, Calkyl or Calkyl substituted with Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl or aryl; Rand Rare each independently selected from hydrogen, a substituted or unsubstituted Cheterocycle, aryl, Calkyl and Calkyl substituted with one or more substituents selected from hydroxy, aryl, aryloxy or a substituted or unsubstituted Cheterocycle. 

This invention comprises the use of compounds of formula (I) wherein the dotted line represents an optional bond; X is oxygen or sulfur; Ris hydrogen, Calkyl, Ar, ArCalkyl, quinolinylCalkyl, pyridylCalkyl, hydroxyCalkyl, CalkyloxyCalkyl, mono- or di(Calkyl)aminoCalkyl, aminoCalkyl, or a radical of formula -Alk-C(&#x2550;O)&#x2014;R, -Alk-S(O)&#x2014;Ror -Alk-S(O)&#x2014;R; R, Rand Reach independently are hydrogen, hydroxy, halo, cyano, Calkyl, Calkyloxy, hydroxyCalkyloxy, CalkyloxyCalkyloxy, aminoCalkyloxy, mono- or di(Calkyl)aminoCalkyloxy, Ar, ArCalkyl, Aroxy, ArCalkyloxy, hydroxycarbonyl, Calkyloxycarbonyl, trihalomethyl, trihalomethoxy, Calkenyl; Rand Reach independently are hydrogen, halo, Ar, Calkyl, hydroxyCalkyl, CalkyloxyCalkyl, Calkyloxy, Calkylthio, amino, hydroxycarbonyl, Calkyloxycarbonyl, CalkylS(O)Calkyl or CalkylS(O)Calkyl; Rand Reach independently are hydrogen, halo, cyano, Calkyl, 4,4-dimethyl-oxazolyl, Calkyloxy or Aroxy; Ris hydrogen, Calkyl, cyano, hydroxycarbonyl, Calkyloxycarbonyl, CalkylcarbonylCalkyl, cyanoCalkyl, CalkyloxycarbonylCalkyl, carboxyCalkyl, hydroxyCalkyl, aminoCalkyl, mono- or di(Calkyl)aminoCalkyl, imidazolyl, haloCalkyl, CalkyloxyCalkyl, aminocarbonylCalkyl, or a radical of formula &#x2014;O&#x2014;R, &#x2014;S&#x2014;R, &#x2014;N&#x2014;RR; Ris hydrogen, halo, cyano, Calkyl, Calkyloxycarbonyl, Ar; Ris hydrogen, Calkyl, Calkyloxy or halo; Ris hydrogen or Calkyl; for the manufacture of a medicament to inhibit smooth muscle cell proliferation.

Method of use of (imidazol-5-yl)methyl-2-quinolinone derivatives to inhibit smooth muscle cell proliferation

a prodrug, N-oxide, addition salt, quaternary amine or stereochemically isomeric form thereof, wherein Land Lare R&#x2014;Y&#x2014; wherein each (R&#x2014;Y)&#x2014; substituent is defined independently of the other; Y is Calkanediyl, Calkenediyl, Calkynediyl, C(&#x2550;O), or a direct bond; Ris hydrogen, cyano, aryl or a substituted or unsubstituted Cheterocycle; &#x2550;Z&#x2014;Z&#x2550;Z&#x2014; represents a radical of formula &#x2550;N&#x2014;N&#x2550;CH&#x2014; (a-1), &#x2550;N&#x2014;CH&#x2550;N&#x2014; (a-2), &#x2550;CH&#x2014;N&#x2550;N&#x2014; (a-3); X is SO, (CH)wherein n is 1 to 4, C(&#x2550;O), C(&#x2550;S), or a direct bond, Ris aryl, Ccycloalkyl, Ccycloalkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted Cheterocycle, Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl, hydroxyCalkyl, hydroxyCalkyloxy, hydroxyCalkylthio and arylCalkylthio, Calkyl or Calkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted Cheterocycle, Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl, hydroxyCalkyl, hydroxyCalkyloxy, hydroxyCalkylthio and arylCalkylthio; Ris aryl, &#x2014;NRR, a substituted or unsubstituted Cheterocycle, or Calkenediyl substituted with a substituted or unsubstituted Cheterocycle or aryl; Ris hydrogen, aryl, Ccycloalkyl, Calkyl or Calkyl substituted with Ccycloalkyl, hydroxycarbonyl, Calkyloxycarbonyl or aryl; Rand Rare each independently selected from hydrogen, a substituted or unsubstituted Cheterocycle, aryl, Calkyl and Calkyl substituted with one or more substituents selected from hydroxy, aryl, aryloxy or a substituted or unsubstituted Cheterocycle.

This invention relates to a method of treatment and dosing regimen for treating mammalian tumors by the discontinuous administration of a farnesyl transferase inhibitor over an abbreviated one to five day dosing schedule.

Dosing regimen

The present invention is concerned with the finding that farnesyl protein transferase inhibitors have radiosensitizing properties which makes them useful for preparing a pharmaceutical composition for administration before, during or after irradiation of a tumor for treating cancer in vivo.

Farnesyl Protein transferase inhibitors with in vivo radiosensitizing properties

The present invention is concerned with the finding that farnesyl protein transferase inhibitors are useful for preparing a pharmaceutical composition for treating arthropathies such as rheumatoid arthritis, osteoarthritis, juvenile arthritis, and gout.

Growing community of inventors

Ambler, PA, United States of America

David William End