Title:
アリールオキシアルキルカルバメート型誘導体、これらの調製方法及び治療における該誘導体の使用
Document Type and Number:
Japanese Patent JP4705590
Kind Code:
B2
Abstract:
O-aminocarbonylmethyl carbamates (I) and their acid addition salts, hydrates and solvates are new. O-aminocarbonylmethyl carbamates of formula (I), and their acid addition salts, hydrates and solvates are new. Y-X-(CH 2) m-CR 1R 3-(CH 2) n-NR 2-CO-OR 4 (I) m and n : 0-3; X : O, S, SO or SO 2; R 1 and R 2hydrogen or 1-3C alkyl, or together form (CH 2) p; p : 1-5; R 3hydrogen, fluoro, hydroxy or Me; R 4CHR 5CONHR 6; R 5hydrogen or 1-6C alkyl; R 6hydrogen, 1-6C alkyl, 3-7C cycloalkyl or 3-7C cycloalkyl(1-6C)alkylene; Y : phenyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, triazinyl, naphthyl, (iso)quinolyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, cinnolinyl, (dihydro)benzofuranyl, (dihydro)benzothienyl, (iso)indolyl, indolinyl, benzimidazolyl, benz(is)oxazolyl, benz(is)othiazolyl, benzotriazolyl, benzoxadiazolyl, benzothiadiazolyl, all optionally substituted by one or more Y 2 or Y 3; Y 2halo, cyano, nitro, 1-8C (fluoro)alkyl, 1-8C (fluoro)alkoxy, 1-8C (fluoro)alkylthio, 3-7C cycloalkyl, 3-7C cycloalkoxy, 3-7C cycloalkyl(1-8C)alkylene, 3-7C cycloalkyl(1-8C)alkoxy, hydroxy, NR 7R 8, NHCOR 7, NHSO 2R 7, COR 7, COOR 7, CONR 7R 8, SO 2R 7, SO 2NR 7R 8, O(1-3C alkylene)O, phenoxy, phenylthio, phenyl(1-8C)-alkylene, phenyl(1-8C)-alkoxy or phenyl(1-8C)-alkylthio; Y 3phenyl, pyridyl, pyrimidyl, pyrazinyl or pyridazinyl, optionally substituted by one or more Y 2; R 7 and R 8hydrogen, 1-6C alkyl, or together form azetidine, pyrrolidine, piperidine, (thio)morpholine, azepine, piperazine (optionally substituted by 1-3C alkyl or benzyl). Provided that when R 1 and R 2 form (CH 2) p, n + p = 2 - 5. An independent claim is also included for preparation of (I) by reacting esters of the formula Y-X-(CH 2) m-CR 1R 3-(CH 2) n-NR 2-CO-O-CHR 5-COOR (IV) with R 6NH 2. R : methyl or ethyl. ACTIVITY : Analgesic; Antiemetic; Neuroprotective; Anticonvulsant; Cardiant; Nephrotropic; Vasotropic; Cytostatic; Immunomodulator; Antiallergic; Antiparasitic; Virucide; Antibacterial; Antiinflammatory; Osteopathic; Ophthalmological; Uropathic. MECHANISM OF ACTION : Inhibition of FAAH (fatty acid amide hydrolase), so increasing the tissue levels of endogenous fatty acid esters and amides, which interact with e.g. cannabinoid and vanilloid receptors. The compound O-(2-amino-2-oxoethyl) 4-(1-naphthoxy)butyl-carbamate (Ia) has IC50 for inhibition of FAAH of 0.047 mu M, when tested by the method of Life Sci., 56 (1995) 1999.
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Inventors:
Abo Abdella, Ahmed
Armario Garcia, Antonio
Floisant, jack
Hohnart, Kristian
Armario Garcia, Antonio
Floisant, jack
Hohnart, Kristian
Application Number:
JP2006548339A
Publication Date:
June 22, 2011
Filing Date:
January 07, 2005
Export Citation:
Assignee:
Sanofui-Aventice
International Classes:
C07C271/16; A61K31/27; A61K31/277; A61K31/40; A61K31/423; A61K31/426; A61K31/4406; A61K31/445; A61K31/47; A61K31/4709; A61K31/472; A61K31/4725; A61K31/505; A61P1/00; A61P1/08; A61P7/12; A61P9/00; A61P9/10; A61P11/00; A61P19/10; A61P25/00; A61P25/04; A61P25/08; A61P25/18; A61P25/20; A61P27/02; A61P29/00; A61P31/04; A61P31/12; A61P33/00; A61P35/00; A61P37/00; A61P43/00; C07C269/06; C07D207/08; C07D211/22; C07D211/46; C07D213/65; C07D215/20; C07D215/26; C07D215/28; C07D217/02; C07D217/24; C07D239/34; C07D263/58; C07D277/20; C07D277/34; C07D401/12
Domestic Patent References:
| JP2006511484A | ||||
| JP2006502229A | ||||
| JP2005516986A | ||||
| JP2004532229A | ||||
| JP2001523695A |
Attorney, Agent or Firm:
Yoshio Kawaguchi
Makoto Ono
Chihiro Watanabe
Kenkyo Kanayama
Katsuma Osaki
Mitsuaki Tsubokura
Makoto Ono
Chihiro Watanabe
Kenkyo Kanayama
Katsuma Osaki
Mitsuaki Tsubokura