Patent EA-001322-B1 (EA)
Title: 2-(4-substituted)-benzylamino-2-propanamide derivatives
Inventor: PEVARELLO PAOLO
IPC: A61K31/165
Filed: 1996-07-05
Abstract: 1. A compound of formula (I)   wherein: n is zero, 1, 2 or 3; X is -O-, -S-, -CH2- or -NH-; each of R and R1 independently is hydrogen, C1-C6 alkyl, halogen, hydroxy, C1-C4 alkoxy or trifluoromethyl; each of R2, R3 and R4 independently is hydrogen, C1-C6 alkyl or C3-C7 cycloalkyl; or a pharmaceutically acceptable salt thereof with a proviso that when X is -S- and R, R1, R2, R3, R4 are hydrogen, n is 1, then X is not -S-. 2. A compound of formula (I), according to claim 1, wherein: n is 1 or 2;  X is -O-, -S- or -NH-; R is hydrogen; R1 is hydrogen or halogen; each of R2, R3 and R4 independently is hydrogen or C1-C4 alkyl; or a pharmaceutically acceptable salt thereof. 3. A compound of formula (I), according to claim 1, wherein: n is 1; X is -O-, -S- or -NH-;  R1 is hydrogen or halogen;  R, R1 R2, R3 and R4 are hydrogen; or a pharmaceutically acceptable salt thereof. 4. A compound selected from the group consisting of: 2-[4-(3-fluorobenzyloxy)benzylamino]-2-methyl-propanamide; 2-[4-(3-chlorobenzyloxy)benzylamino]-2-methyl-propanamide; 2-[4-(4-chlorobenzyloxy)benzylamino]-2-methyl-propanamide; 2-[4-(3-bromobenzyloxy)benzylamino]-2-methyl-propanamide; 2-[4-(4-fluorobenzyloxy)benzylamino]-2-methyl-propanamide; 2-[4-(2-fluorobenzyloxy)benzylamino]-2-methyl-propanamide; 2-[4-(3-fluorobenzylamino)benzylamino]-2-methyl-propanamide; 2-{[4-(3-fluorobenzyloxy)benzyl]-methylamino}-2-methyl-propanamide; 2-[4-(3-fluorobenzyloxy)benzylamino]-2-methyl-N-methyl-propanamide 2-{[4-(3-chlorobenzyloxy)benzyl]methylamino}-2-methyl-propanamide; and 2-{[4-(3-bromobenzyloxy)benzyl]methylamino}-2-methyl-propanamide, or a pharmaceutically acceptable salt thereof. 5. A process for the preparation of a compound of formula (I):   wherein: n is zero, 1, 2 or 3; X is -O-, -S-, -CH2- or -NH-; each of R and R1 independently is hydrogen, C1-C6 alkyl, halogen, hydroxy, C1-C4 alkoxy or trifluoromethyl; R2 ishydrogen or C1-C6 alkyl; each of R3 and R4 independently is hydrogen, C1-C6 alkyl or C3-C7 cycloalkyl; or a pharmaceutically acceptable salt, the process comprising: a) reacting a compound of formula (II)   wherein n, R, R1 and X are as defined in claim 1, with a compound of formula (III)   wherein R3 and R4 are as defined in claim 1, in the presence of a reducing agent, thus obtaining a compound of formula (I) in which R2 is hydrogen; and b) reacting a compound of formula (IV)   wherein R, R1 R2, R3 and R4, n and X are as defined in claim 1, with a compound of formula (V) or (VI) R'2W (V)                  R"2CHO (VI), wherein W is a halogen atom; R'2 is a C1-C6 alkyl and R"2 is hydrogen or C1-C5 alkyl, in case of the compound (VI) in the presence of a reducing agent thus obtaining a compound of the formula (I), in which R2 is C1-C6 alkyl; and optionally, converting a compound of the formula (I) into a pharmaceutically acceptable salt and/or, optionally, converting a salt into a free compound. 6. A pharmaceutical composition containing a suitable carrier and/or diluent and, as an active principle, a compound of formula (I), as defined in claim 1   wherein: n is zero, 1, 2 or 3; X is -O-, -S-, -CH2- or -NH-; each of R and R1 independently is hydrogen, C1-C6 alkyl, halogen, hydroxy, C1-C4 alkoxy or trifluoromethyl; each of R2, R3 and R4 independently is hydrogen, C1-C6 alkyl or C3-C7 cycloalkyl; or a pharmaceutically acceptable salt thereof.