Title:
2-ヒドロキシテトラヒドロフランの新規誘導体及びそれらの医薬品としての使用
Document Type and Number:
Japanese Patent JP4686474
Kind Code:
B2
Abstract:
3-Amino-2-hydroxytetrahydrofuran derivatives (I), N-substituted by a di- or tripeptide side-chain terminated by a dibenzazepine, phenoxazine, phenothiazine or phenazine group, are new. Tetrahydrofuran derivatives of formula (I) and their salts are new. [Image] A : a tricyclic group of formula (i); R 1>, R 2>, R 4>-R 6>H, halo, OH, alkyl, alkoxy, CN, NO 2or NR 7>R 8>; R 7>, R 8>H, alkyl or COR 9>; R 9>H, alkyl or alkoxy; R 3>H, alkyl or COR 10>; R 10>H, alkyl or alkoxy; W : CH 2CH 2, CH=CH, O, S or NR 11>; R 11>H or alkyl; X : CO, Y-CO, O-Y-CO or NR 12>-Y-CO; Y : alkylene or haloalkylene; R 12>H, alkyl or COR 9>; R 13>H, alkyl, haloalkyl or alkoxy; AA : a natural aminoacid (optionally having chemically reactive side-chain functions protected, specifically as (ar)alkyl ester for carboxy, as (ar)alkyl carbamate or (ar)alkyl carboxamide for amino or as (ar)alkyl (thio)ether or (ar)alkyl ester for alcohol or thiol) or NR 14>-(CH 2) p-CR 15>R 16>-CO, or (AA) 2may also be a carbapeptide of formula NR 17>-(CH 2) 3-CHR 18>-CO; p : 0 or 1; R 14>, R 15>, R 17>, R 18>H or alkyl; R 16>H, alkyl, haloalkyl, phenyl, cycloalkyl, cycloalkylalkyl or alkenyl, or CR 15>R 16>3-7C (preferably 3-6C) cycloalkylidene; n : 2 or 3; R : H, alkyl or COR 19>, and R 19>alkyl. [Image] ACTIVITY : Antiinflammatory, Immunosuppressive; Cardiant; Vasotropic; Cerebroprotective; Neuroprotective; Osteopathic; ophthalmological; virucide; antirheumatic; antiarthritic; antiulcerative; hypotensive; antibacterial; hemostatic; thrombolytic; anticoagulant; vulnerary; anticonvulsant; nootropic; antiparkinsonian; auditory; antiarteriosclerotic; dermatological; anti-HIV; antiparasitic; antidiabetic; cytostatic. MECHANISM OF ACTION : Calpain inhibitor; Lipid peroxidation inhibitor. In a test, N-(10H-phenothiazin-2-ylcarbonyl)-L-leucyl-L-leucyl-N 1>-((3S)-2-hydroxytetrahydrofuran-3-yl)-L-leucinamide (Ia) exhibited an IC 50value of less than 5 mu M for inhibition of human calpain I.
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Inventors:
Ouvin, Serge
Syabrier de la Sounier, Pierre, Etienne
Syabrier de la Sounier, Pierre, Etienne
Application Number:
JP2006543581A
Publication Date:
May 25, 2011
Filing Date:
December 08, 2004
Export Citation:
Assignee:
IPSEN PHARMA S.A.S.
International Classes:
C07K5/062; A61K38/00; A61P9/00; A61P19/10; A61P21/04; A61P25/02; A61P25/28; A61P27/12; A61P29/00; A61P31/12; A61P35/00; A61P37/06; A61P39/06; C07K5/06; C07K5/065; C07K5/068; C07K5/078; C07K5/097; C07K5/117
Domestic Patent References:
| JP2003513092A | ||||
| JP2001505889A | ||||
| JP10101558A | ||||
| JP10512257A |
Other References:
Bioorg. Med. Chem. Lett., 1999, Vol.9, p.2365-2370
Attorney, Agent or Firm:
Takao Hamano
Teruichi Hirai
Teruichi Hirai