Title:
ヘテロアリール-アルキルカーバメート誘導体、それらの製造方法、及び、FAAH酵素インヒビターとしてのそれらの使用
Document Type and Number:
Japanese Patent JP4824668
Kind Code:
B2
Abstract:
Carbamoylalkyl N-((hetero)aryl-substituted alkyl)-carbamates (I) are new. Carbamates of formula (I) and their acid addition salts, hydrates and solvates are new. A : one or more of X, Y and/or Z; X : CH 2 (optionally substituted (os) by 1 or 2 of alkyl, cycloalkyl or cycloalkyl-(1-3C) alkyl); Y : 2C alkenylene (os by 1 or 2 of alkyl, cycloalkyl or cycloalkyl-(1-3C) alkyl) or 2C alkynylene; Z : 3-7C cycloalkylidene or 3-7C cycloalkylene; n : 1-7; R 1R 2 (os by one or more groups R 2 and/or R 3); R 2mono- or fused heteroaryl or naphthalenyl; R 3halo, CN, NO 2, alkyl, alkoxy, OH, alkylthio, fluoroalkyl, fluoroalkoxy, fluoroalkylthio, NR 5R 6, NR 5COR 6, NR 5COOR 6, NR 5SO 2R 6, COR 5, COOR 5, CONR 5R 6, SO 2R 5, SO 2NR 5R 6 or 1-3C alkylenedioxy; R 4phenyl, phenoxy, benzyloxy, naphthalenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl (all os by one or more groups R 3); R 5, R 6H or alkyl; or NR 5R 6azetidino, pyrrolidino, piperidino, morpholino, thiomorpholino, azepino or piperazino (all os by alkyl or benzyl); R 7H or alkyl; R 8H, alkyl, cycloalkyl or cycloalkyl-(1-3C) alkyl; alkyl moieties have 1-6C and cycloalkylene moieties 3-7C unless specified otherwise. Full definitions are given in the "Definitions" section. Independent claims are included for: (A) the preparation of (I); and (B) carbamate ester and oxazolidinedione derivative intermediates of formulae (IV) and (VII) as new compounds, provided that (i) ethyl 2-((((2-(5-hydroxy-1H-indol-3-yl)-ethyl)-amino)-carbonyl)-oxy)-propanoate and ethyl 2-((((2-(5-(phenylmethoxy)-1H-indol-3-yl)-ethyl)-amino)-carbonyl)-oxy)-propanoate are excluded as (IV) and (ii) 2-(2-(DOOD')-ethyl)-1-methyl-pyridinium iodide, 2-(2-(DOOD')-ethyl)-5-ethyl-1-methyl-pyridinium iodide, 5-methyl-3-(2-(2-(2- or 4-pyridinyl)-ethyl)-DOOD hydrochloride, 3-(5-imidazo-(1,2-a)-pyridin-5-ylpentyl)-DOOD, 3-(2-5-methyl-4-thiazolyl)-ethyl)-DOOD, 3-(2-(1H-pyrrol-2-yl)-ethyl)-DOOD, 3-(2-(2-thienyl)-ethyl)-DOOD, 3-(3-(2-thienyl)-propyl)-DOOD, 3-(4-(2-thienyl)-butyl)-DOOD, 5-(methyl or ethyl)-3-(2-(2-thienyl)-ethyl)-DOOD, 3-(2-(3-thienyl)-ethyl)-DOOD, 3-(2-(5-(methyl, acetyl or bromo)-2-thienyl)-ethyl)-DOOD, 5-(2-(DOOD')-ethyl) -2-thiophene-carboxaldehyde, 3-(3-(1-indolinyl)-propyl)-DOOD, 3-(3-(1-indolinyl)-propyl)-5-methyl-DOOD, 3-(2-(2- or 4-pyridinyl)-ethyl)-DOOD, 3-(2-(5-ethyl-2-pyridinyl)-ethyl)-5-(methyl, ethyl or isopropyl)-DOOD, 5-(ethyl or isopropyl)-3-(2-(2- or 4-pyridinyl)-ethyl)-DOOD and 3-(2-(5-ethyl-2-pyridinyl)-ethyl-DOOD are excluded as (VII). R : Me or Et; DOOD' : 2,4-dioxo-3-oxazolidinyl; DOOD : 2,4-oxazolidinedione. [Image] ACTIVITY : Analgesic; antimigraine; auditory; antiemetic; anorectic; immunomodulator; neuroleptic; relaxant; tranquilizer; antidepressant; neuroprotective; antiparkinsonian; nootropic; anticonvulsant; cerebroprotective; nephrotropic; cardiant; hypotensive; antiarrythmic; antiarteriosclerotic; vasotropic; cytostatic; immunosuppressive; antipsoriatic; dermatological; antianemic; antiallergic; antiparasitic; virucide; antibacterial; anti-HIV; antiinflammatory; antiarthritic; antirheumatic; osteopathic; antigout; ophthalmological; antitussive; antiasthmatic; antiulcer; antidiarrheic; uropathic. In phenylbenzoquinone-induced writhing tests for analgesic activity in mice, the most active compounds (I) (not specified) inhibited writhing by 35-70% at doses of 1-30 mg/kg p.o. or i.p. MECHANISM OF ACTION : Fatty acid amidohydrolase (FAAH) inhibitor. 2-Amino-2-oxoethyl (5-(isoquinolin-4-yl)-pentyl)-carbamate (Ia) had IC 5 0 267 nM for inhibition of FAAH.
Inventors:
Abu Abdella, Ameds
Barcille, Regine
Orna Ale, Kristian
Labe, Antoine
Barcille, Regine
Orna Ale, Kristian
Labe, Antoine
Application Number:
JP2007500260A
Publication Date:
November 30, 2011
Filing Date:
February 25, 2005
Export Citation:
Assignee:
Sanofui-Aventice
International Classes:
C07D213/53; A61K31/4045; A61K31/415; A61K31/4164; A61K31/42; A61K31/421; A61K31/4245; A61K31/437; A61K31/44; A61K31/47; A61K31/472; A61K31/50; A61K31/505; A61P1/00; A61P1/08; A61P1/12; A61P9/00; A61P11/00; A61P13/02; A61P13/12; A61P19/10; A61P25/04; A61P25/08; A61P25/18; A61P25/20; A61P25/28; A61P27/02; A61P29/00; A61P31/04; A61P31/12; A61P33/00; A61P35/00; A61P37/00; A61P37/08; A61P43/00; C07C271/10; C07C271/12; C07D209/08; C07D213/40; C07D213/54; C07D215/04; C07D215/12; C07D215/227; C07D217/02; C07D217/12; C07D217/14; C07D231/12; C07D233/54; C07D233/64; C07D235/06; C07D235/14; C07D237/08; C07D239/26; C07D239/42; C07D261/08; C07D261/14; C07D263/32; C07D271/06; C07D273/02; C07D413/04; C07D471/04; C07D215/22
Domestic Patent References:
| JP2007527397A | 2007-09-27 | |||
| JP2006511484A | 2006-04-06 | |||
| JP2006502229A | 2006-01-19 | |||
| JP2006525293A | 2006-11-09 | |||
| JP4617292B2 | 2011-01-19 | |||
| JP2007524706A | 2007-08-30 |
Foreign References:
| US3742022A | 1973-06-26 |
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