Title:
ロタマーゼの阻害のための新規化合物およびその使用
Document Type and Number:
Japanese Patent JP2005539072
Kind Code:
A
Abstract:
In the manufacture of medicament for treating e.g. abnormal cell proliferation or abnormal mitosis, substituted carbocyclic compound is used. In the manufacture of medicament for treating e.g. abnormal cell proliferation or abnormal mitosis, substituted carbocyclic compound of formula A-X-Y (I) is used. A : cycloalkyl, heterocyclyl or (hetero)aryl (all optionally substituted); X : X 1or X 2; X 1-[(CR aR b) n-NR c-CO-NR d-(CR aR b) m] t-, -[(CR aR b) n-NR c-CS-NR d-(CR aR b) m] t-, -[(CR aR b) n-NR c-C(N-CN)-NR d-(CR aR b) m] t-, -[(CR aR b) n-NR c-C(N-R e)-NR d-(CR aR b) m] t-, -[(CR aR b) n-CO-NR c-(CR aR b) m] t-, -[(CR aR b) n-NR c-(CR aR b) m] t-, -[(CR aR b) n-NR c-CO-O-(CR aR b) m] t-, -[(CR aR b) n-O-CO-NR c-(CR aR b) m] t-, -L(CR aR b) n-O-(CR aR b) m] t- or -[(CR aR b) n-SR c-(CR aR b) m] t-; X 2-[(CR aR b) n-CO-(CR aR b) m] t-, -[(CR aR b) n-CS-(CR aR b) m] t-, -[(CR aR b) n-NR c-CO-(CR aR b) m] t-, -[(CR aR b) n-CO-NR c-(CR aR b) m] t-, -[(CR aR b) n-NR c-CS-(CR aR b) m] t-, -[(CR aR b) n-CS-NR c-(CR aR b) m] t-, -[(CR aR b) n-NR c-SO 2-(CR aR b) m] t-, -[(CR aR b) n-SO 2-NR c-(CR aR b) m] t-, -[(CR aR b) n-SO-(CR aR b) m] t-, -[(CR aR b) n-SO 2-(CR aR b) m] t- or -[(CR aR b) n] t-; n, m and t : 0 - 10; R a- R eH, (cyclo)alkyl, (hetero)aryl or heterocyclyl; Y : (cyclo)alkyl, cycloalkenyl or optionally mono- to poly-unsaturated heterocyclyl, (hetero)aryl (all optionally substituted). Provided that: (a) When n is 0, then m is different from 0; (b) When m is 0, then n is different from 0; and (c) Y is other than peptide. ACTIVITY : Neuroprotective; Nootropic; Anticonvulsant; Antiparkinsonian; Cerebroprotective; CNS-Gen.; Muscular-Gen.; Vasotropic; Antiinflammatory; Immunosuppressive; Antirheumatic; Antiarthritic; Nephrotropic; Dermatological; Gastrointestinal-Gen.; Antiasthmatic; Hemostatic; Respiratory-Gen.; Cardiant; Thrombolytic; Antiarteriosclerotic; Tranquilizer; Immunomodulator; Antimicrobial; Fungicide; Antibacterial; Virucide; Anti-HIV; Antidiarrheic; Antipyretic; Gynecological; Antitubercular; Tuberculostatic; Antiparasitic; Cardiovascular-Gen.; Cytostatic; Antipsoriatic; Vulnerary. MECHANISM OF ACTION : Rotamase inhibitor; Cancer cell growth inhibitor. 1-Adamantan-1-yl-3-(3,5-dichloro-4-hydroxy-phenyl)-urea (A) was tested for peptidyl-prolyl cis-trans isomerase (PPlase) activity of hPin1 using protease-coupled PPlase assay as given in Fischer et al. (Mech, C. Determination of enzymatic catalysis fort he cis-trans-isomerization of peptide binding in proline-containing peptides. [German] Biomed. Biochem. Acta 1984, 43, 1101-1111. The IC 50of (A) was found to be less than 1 MicroM.
Inventors:
Knole, Yochen
Stokowski, Mike
Hummel, Gerd
Tratler, Thomas
Jobron, Lawrence
Cristner, Claudia
Scharn, Dirk
Strages, Lorant
Gippson, Christoph
Osterkamp, Frank
Stokowski, Mike
Hummel, Gerd
Tratler, Thomas
Jobron, Lawrence
Cristner, Claudia
Scharn, Dirk
Strages, Lorant
Gippson, Christoph
Osterkamp, Frank
Application Number:
JP2004537125A
Publication Date:
December 22, 2005
Filing Date:
September 18, 2003
Export Citation:
Assignee:
JERINI AG
International Classes:
C07D295/12; A61K31/135; A61K31/137; A61K31/155; A61K31/165; A61K31/167; A61K31/17; A61K31/18; A61K31/216; A61K31/22; A61K31/27; A61K31/277; A61K31/341; A61K31/36; A61K31/381; A61K31/4164; A61K31/4184; A61K31/428; A61K31/4409; A61K31/47; A61K31/5375; A61P1/04; A61P1/12; A61P1/16; A61P7/02; A61P7/04; A61P9/00; A61P9/10; A61P11/00; A61P11/06; A61P13/08; A61P13/10; A61P13/12; A61P15/00; A61P17/00; A61P17/02; A61P17/06; A61P19/02; A61P21/04; A61P25/00; A61P25/02; A61P25/14; A61P25/16; A61P25/28; A61P27/02; A61P29/00; A61P31/00; A61P31/04; A61P31/06; A61P31/10; A61P31/12; A61P31/14; A61P31/16; A61P31/18; A61P31/22; A61P33/00; A61P33/02; A61P35/00; A61P35/02; A61P37/00; A61P37/06; A61P43/00; C07C215/76; C07C215/78; C07C217/58; C07C233/25; C07C233/62; C07C233/75; C07C271/28; C07C275/34; C07C275/36; C07C275/40; C07C275/42; C07C311/08; C07C311/13; C07C317/32; C07C323/32; C07C323/37; C07C323/41; C07C335/18; C07D213/75; C07D215/36; C07D233/64; C07D235/14; C07D277/66; C07D295/18; C07D307/52; C07D307/68; C07D317/60; C07D317/66; C07D333/28; C07D333/34; (IPC1-7): C07C215/76; A61K31/137; A61K31/167; A61K31/17; A61K31/18; A61K31/216; A61K31/22; A61K31/27; A61K31/277; A61K31/341; A61K31/36; A61K31/381; A61K31/4164; A61K31/4184; A61K31/428; A61K31/4409; A61K31/47; A61K31/5375; A61P1/04; A61P1/12; A61P1/16; A61P7/02; A61P7/04; A61P9/00; A61P9/10; A61P11/00; A61P11/06; A61P13/08; A61P13/10; A61P13/12; A61P15/00; A61P17/00; A61P17/02; A61P17/06; A61P19/02; A61P21/04; A61P25/00; A61P25/02; A61P25/14; A61P25/16; A61P25/28; A61P27/02; A61P29/00; A61P31/00; A61P31/04; A61P31/06; A61P31/10; A61P31/12; A61P31/14; A61P31/16; A61P31/18; A61P31/22; A61P33/00; A61P33/02; A61P35/00; A61P35/02; A61P37/00; A61P37/06; A61P43/00; C07C215/78; C07C217/58; C07C233/25; C07C233/62; C07C233/75; C07C271/28; C07C275/34; C07C275/36; C07C275/40; C07C275/42; C07C311/08; C07C311/13; C07C317/32; C07C323/32; C07C323/37; C07C323/41; C07C335/18; C07D213/75; C07D215/36; C07D233/64; C07D235/14; C07D277/66; C07D295/12; C07D295/18; C07D307/52; C07D307/68; C07D317/60; C07D317/66; C07D333/28; C07D333/34
Domestic Patent References:
| JPH08510448A | 1996-11-05 |
Foreign References:
| WO2002059080A2 | 2002-08-01 | |||
| US6093742A | 2000-07-25 |
Attorney, Agent or Firm:
Hajime Tsukuni
Fumio Shinoda
Fumio Shinoda