Patent RU-2318816-C2 (RU)
Title: 4-substituted imidazole-2-thiones and imidazole-2-ones as agonists of alpha2b- and alpha2c-adrenergic receptors
IPC: A61P21/02
Filed: 2003-05-16
Granted: 2008-03-10
Abstract: FIELD: organic chemistry, medicine, pharmacology. 
     SUBSTANCE: invention relates to compounds of the formula:  , wherein variable value Y in ring is not obligatory and represents heteroatom chosen from nitrogen (N), oxygen (O) and sulfur (S) atoms under condition that N atom is trivalent and O or S atoms are bivalent; k means a whole number from 0 to 1; n means a whole number 0, 1 or 2; p means a whole number 0, 1 or 2; X means O or S atom; dotted lines represent a bond or its absence under condition that ring comprises only a single double bond and two adjoining lines are not a bond; R 1 , R 2 , R 3  and R represent independently hydrogen atom (H), phenyl wherein indicated phenyl group is substituted optionally with one, two or three substitutes represented by (C 1 -C 6 )-alkyl, -SO 3 H, -N 3 , halogen atom, -CN, -NO 2 , -NH 2 , (C 1 -C 6 )-alkoxy-, (C 1 -C 6 )-thioalkoxy-, (C 1 -C 6 )-alkylamino-, (C 1 -C 6 )-dialkylamino-group, (C 2 -C 6 )-alkynyl, (C 2 -C 6 )-alkenyl; 5- or 6-membered heteroaryl comprising from 1 to 3 heteroatoms chosen from O, S and N atoms wherein indicated heteroaryl groups are substituted optionally and independently with one, two or three substitutes represented by (C 1 -C 6 )-alkyl, -SO 3 H, -N 3 , halogen atom, -CN, -NO 2 , -NH 2 , (C 1 -C 6 )-alkoxy- (C 1 -C 6 )-thioalkoxy-, (C 1 -C 6 )-alkylamino-, (C 1 -C 6 )-dialkylamino-group, (C 2 -C 6 )-alkynyl, (C 2 -C 6 )-alkenyl, or indicated groups R 1 , R 2 , R 3  and R 4  represent independently alkyl comprising from 1 to 4 carbon atoms, cycloalkyl comprising from 3 to 5 carbon atoms, -CH 2 CN, -CH 2 SR 5 , -CH 2 NR 6 R 6 , -COR 5 , -CH 2 OR 5 , -OR 6 , -SR 6 , -NR 6 R 6 , alkenyl comprising from 1 to 4 carbon atoms, alkynyl comprising from 1 to 4 carbon atoms, cycloalkyl comprising from 3 to 6 carbon atoms, fluorine atom, chlorine atom, bromine atom, iodine atom, -CF 3  or -CN, oxygen atom bound by a double bond with ring carbon under condition that adjoining dotted line inside of ring means absence of a bond; R 5  means H, -OR 7 , alkyl comprising from 1 to 4 carbon atoms, -CF 3 , cycloalkyl comprising from 3 to 6 carbon atoms, phenyl, phenyl substituted with one or two alkyl groups comprising from 1 to 4 carbon atoms, fluorine atom, chlorine atom, bromine atom, iodine atom or -CF 3 , either R 5  represents 5- or 6-membered heteroaryl comprising from 1 to 3 heteroatoms chosen from O, S and N atoms, and 5- or 6-membered heteroaryl comprising from 1 to 3 heteroatoms chosen from O, S and N atoms substituted with one or two alkyl groups comprising from 1 to 4 carbon atoms, fluorine atom, chlorine atoms, bromine atom, iodine atom or -CF 3 ; R 6  means H, alkyl comprising from 1 to 4 carbon atoms, allyl, cycloalkyl comprising from 3 to 6 carbon atoms, phenyl, phenyl substituted with one or two alkyl groups comprising from 1 to 4 carbon atoms, fluorine atom, chlorine atom, bromine atom, iodine atom or -CF 3 , either R 6  represents 5- or 6-membered heteroaryl comprising from 1 to 3 heteroatoms chosen from O, S and N atoms, either 5- or 6-membered heteroaryl comprising from 1 to 3 heteroatoms chosen from O, S and N atoms substituted with one or two alkyl groups comprising from 1 to 4 carbon atoms, fluorine atom, chlorine atom, bromine atom, iodine atom or -CF 3 ; R 7  means H, alkyl comprising from 1 to 4 carbon atoms, allyl, cycloalkyl comprising from 3 to 6 carbon atoms, phenyl, phenyl substituted with one or two alkyl groups comprising from 1 to 4 carbon atoms, fluorine atom, chlorine atom, bromine atom, iodine atom or -CF 3 ; R 1  and R 2  or R 2  and R 3 , or R 3  and R 4  can form in common a ring with corresponding carbon atoms to which they are bound; fragments represented by substitutes R 1  and R 2  or R 2  and R 3 , or R 3  and R 4  have the following formulae (i):  , (ii):  , (iii):  , (iv):   or (v):   - wherein m means a whole number from 0 to 3; R 8  represents independently H, alkyl comprising from 1 to 6 carbon atoms, alkenyl comprising from 2 to 6 carbon atoms, alkynyl comprising from 2 to 6 carbon atoms, -SO 3 H, -N 3 , -CN, - NO 2 , F, Cl, Br, J atoms, -CF 3 , -COR 9 , -CH 2 OR 9 , -OR 10 , -SR 10 , (C 1 -C)-alkylamino- or (C 1 -C 6 )-dialkylamino-group wherein R 9  means H, alkyl comprising from 1 to 6 carbon atoms, or -OR 10  wherein R 10  represents independently H or alkyl comprising from 1 to 6 carbon atoms. Also, invention relates to compounds of the formula:   and  , and to a method for activation of alpha 2B - or alpha 2C -adrenergic receptors. Invention provides synthesis of novel biologically active compound possessing activity as agonists of alpha-2B and alpha-2C-adrenergic receptors. 
     EFFECT: valuable medicinal properties of compounds. 
     34 cl, 5 tbl, 33 ex