Patent RU-2266905-C2 (RU)
Inventor: OKADA TOSIMI
IPC: C07D453/02
Filed: 2000-09-27
Granted: 2005-12-27
Abstract: FIELD: organic chemistry, chemical technology, medicine, biochemistry. 
     SUBSTANCE: invention relates to quinuclidine compounds of the formula (I)  , its salts or their hydrates wherein R 1  represents hydroxyl group; W represents: (1) -CH 2 -CH 2 -; 2) -CH=CH-, or 3) -C≡C-; HAr represents 5-10-membered aromatic heterocycle comprising 1-2 heteroatoms taken among nitrogen atom and sulfur atom that in addition to the group -X-Ar can be substituted with 1-3 groups taken among: (1) halogen atom; (2) (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl or (C 2 -C 6 )-alkynyl group substituted optionally with: (a) hydroxy-group; (b) (C 1 -C 6 )-alkoxycarbonyl; (c) (C 1 -C 6 )-alkanoyl optionally substituted with (C 1 -C 6 )-alkoxy-group; (d) hydroxylated (C 3 -C 8 )-cycloalkyl; (e) (C 1 -C 6 )-alkoxy-group; (f) 5-6-membered aromatic heterocycle comprising 1-3 heteroatoms taken among nitrogen atom, sulfur atom and oxygen atom, or (g) cyano-group; (3) (C 1 -C 6 )-alkoxy-group optionally substituted with: (a) hydroxy-group; (b) (C 1 -C 6 )-alkoxy-group optionally substituted with (C 1 -C 6 )-alkoxy-group; (c) halogen atom; (d) 4-6-membered nonaromatic heterocycle comprising 1-3 heteroatoms taken among nitrogen atom, sulfur atom and oxygen atom; (e) 5-6-membered aromatic heterocycle comprising 1-3 heteroatoms taken among nitrogen atom, sulfur atom and oxygen atom; (4) (C 1 -C 6 )-alkylthio-group optionally substituted with (C 1 -C 6 )-alkoxy-group or hydroxy-group; (5) 5-6-membered heterocyclyloxy-group comprising 1-2 oxygen atoms in heterocycle; (6) amino-group represented by the formula: -N(R 3 )R 4  wherein R 3  and R 4  are similar or different and each represents hydrogen atom or group taken among: (a) (C 1 -C 6 )-alkyl group; (b) (C 1 -C 6 )-alkoxy-(C 1 -C 6 )-alkyl group; (c) carbonyl substituted with (C 6 -C 14 )-aryl; (d) (C 6 -C 14 )-arylsulfonyl or (e) 4-6-membered nonaromatic heterocycle comprising  1-3 heteroatoms taken among nitrogen atom, sulfur atom and oxygen atom; (7) (C 3 -C 8 )-cycloalkyl or cycloalkenyl hydrocarbon group optionally substituted with: (a) oxo-group or (b) hydroxy-group; (8) (C 6 -C 14 )-aromatic hydrocarbon ring optionally substituted with: (a) (C 1 -C 4 )-alkylene dioxy-group or (b) hydroxy-group; (9) 5-6-membered aromatic heterocycle comprising 1-3 heteroatoms taken among nitrogen atom, sulfur atom and oxygen atom optionally substituted with: (a) cyano-group or (b) (C 1 -C 6 )-alkoxy-group; (10) 4-6-membered nonaromatic heterocycle comprising 1-3 heteroatoms taken among nitrogen atom, sulfur atom and oxygen atom optionally substituted with one or some groups taken among: (a) hydroxy-group; (b) halogen atom; (c) cyano-group; (d) (C 1 -C 6 )-alkoxycarbonyl; (e) (C 1 -C 6 )-alkyl; (f) (C 1 -C 6 )-alkoxy-group that is optionally substituted with halogen atom or (C 1 -C 6 )-alkoxy-group; (g) (C 1 -C 6 )-alkanoyl; (h) (C 1 -C 6 )-alkoxy-(C 1 -C 6 )-alkyl; (i) oxo-group; (j) (C 1 -C 4 )-alkylenedioxy-group; (k) (C 3 -C 8 )-cycloalkylalkoxy-group or (C 3 -C 8 )-cycloalkenylalkoxy-group; (11) carbamoyl of the formula: -CO-N(R 5 )R 6  wherein R 5  and R 6  can be similar or different and represent hydrogen atom, (C 6 -C 14 )-aryl wherein indicated aryl is optionally substituted with halogen atom, or (C 3 -C 8 )-cycloalkyl; or R 5  and R 6  form in common 3-6-membered ring; (12) carbonyl optionally substituted with (C 1 -C 6 )-alkoxy-group; X represents: (1) a simple bond; (2) (C 1 -C 6 )-alkylene chain; (3) (C 1 -C 6 )-alkenylene chain; (4) (C 1 -C 6 )-alkynylene chain; or (5) formula: -Q- wherein Q represents oxygen atom or sulfur atom; Ar represents: (1) (C 6 -C 14 )-aromatic hydrocarbon ring optionally substituted with one or some groups taken among: (a) halogen atom; (b) (C 1 -C 4 )-alkoxy-group or (c) (C 1 -C 6 )-alkylthio-group; or (2) 5-6-membered aromatic heterocycle comprising 1-2 heteroatoms taken among nitrogen atom and sulfur atom. Compounds of the formula (I) show inhibitory activity with respect to a squalene-synthesizing enzyme. Also, the invention relates to an inhibitor of squalene-synthesizing enzyme and the corresponding medicinal composition based on compound of the invention, a method for prophylaxis and treatment of disease wherein inhibition of squalene-synthesizing enzyme is effective. Also, invention proposes some methods for preparing compounds of the formula (I). 
     EFFECT: improved preparing method, valuable of medicinal and biochemical properties of com[pounds and composition. 
     25 cl, 10 tbl, 214 ex