Patent RU-2293735-C2 (RU)
Title: Derivatives of nor-seco-chimbacine, pharmaceutical composition and method for inhibiting based on thereof
Inventor: CHAKALAMANNIL SEHMJUEHL
IPC: A61K31/497
Filed: 2001-06-13
Granted: 2007-02-20
Abstract: FIELD: organic chemistry, medicine. 
     SUBSTANCE: invention relates to compound represented by the structural formula:   or its pharmaceutically acceptable salt wherein Z represents -(CH 2 ) n -; double dotted line represents a double bond; n = 0-2; R 1  and R 2  are chosen independently from the group comprising hydrogen atom (H), alkyl with 1-6 carbon atoms; R 3  means H, hydroxy-, alkoxy-group with 1-6 carbon atoms, -C(O)OR 17  or alkyl with 1-6 carbon atoms; Het means monocyclic heteroaromatic group consisting of 6 atoms and comprising 5 carbon atoms and one heteroatom chosen from nitrogen atom (N) and wherein Het is bound through ring carbon atom and wherein Het-group has one substitute W chosen independently from the group comprising bromine atom (Br), heterocycloalkyl representing group consisting of 4 carbon atoms and one heteroatom chosen from N; heterocycloalkyl representing group consisting of 4 carbon atoms and one heteroatom chosen from N substituted with OH-substituted alkyl with 1-6 carbon atoms or =O; R 21  -aryl-NH-; -C(=NOR 17 )R 18 ; R 21 -aryl; R 41 -heteroaryl representing group consisting of 5-6 atoms comprising 3-5 carbon atoms and 1-4 heteroatoms chosen independently from the group: N, S and O; R 8  and R 10  are chosen independently from group comprising R 1 ; R 9  means H; R 11  is chosen from group comprising R 1  and -CH 2 OBn wherein Bn means benzyl; B means -(CH 2 ) n4 CR 12 =CR 12a (CH 2 ) n5 ; n 4  and n 5  mean independently 0; R 12  and R 12a  are chosen independently from group comprising H, alkyl with 1-6 carbon atoms; X means -O-; Y means =O; R 15  is absent as far as double dotted line mean a simple bond; R 16  means lower alkyl with 1-6 carbon atoms; R 17  and R 18  are chosen independently from group comprising H, alkyl with 1-6 carbon atoms; R 21  means 1-3 substituted chosen independently from group comprising hydrogen atom, -CN, -CF 3 , halogen atom, alkyl with 1-6 carbon atoms and so on; R 22  is chosen independently from group comprising hydrogen atom; R 24 -alkyl with 1-10 carbon atoms; R 25 -aryl and so on; R 23  is chosen independently from group comprising hydrogen atom, R 24 -alkyl with 1-10 carbon atoms, R 25 -aryl and -CH 2 OBn; R 24  means 1-3 substitutes chosen independently from group comprising hydrogen atom, halogen atom, -OH, alkoxy-group with 1-6 carbon atoms; R 25  means hydrogen atom; R 41  means 1-4 substitutes chosen independently from group comprising hydrogen atom, alkyl with 1-6 carbon atoms and so on. Also, invention relates to a pharmaceutical composition possessing the inhibitory activity with respect to receptors activated by protease and comprising the effective dose of derivative of nor-seco-chimbacine of the formula (I) and a pharmaceutically acceptable excipient. Also, invention relates to methods for inhibition of thrombin and cannabinoid receptors comprising administration in mammal derivative of nor-seco-chimbacine of the formula (I) in the effective dose as active substance. Invention provides derivatives of nor-seco-chimbacine as antagonists of thrombin receptors. 
     EFFECT: valuable medicinal and biological properties of compounds and pharmaceutical composition. 
     8 cl, 1 tbl, 18 ex