Patent RU-94040841-A (RU)
Inventor: ANDERSON PAUL CATES
IPC: A61K31/506
Filed: 1993-03-12
Abstract: FIELD: organic chemistry. SUBSTANCE: product: derivatives of pipecolinic acid of the formula (I)where X - groups ROC(O),RC(O),RNRC(O) where Rmeans lower alkyl, lower cycloalkyl, unsubstituted phenyl or phenyl monosubstituted with halide, hydroxyl, lower alkyl or lower alkoxyl, or disubstituted with lower alkyl or halide; phenyl-lower alkyl phenyl part of that can be substituted with halide, hydroxyl, lower alkyl or lower alkoxyl; 1-naphthyl, 2-naphthyl, 5- or 6-membered monovalent heterocyclic residue that contains 1 or 2 heteroatoms from group involving nitrogen, oxygen and sulfur and can be substituted with lower alkyl, 2-quinolinyl or 3-quinolinyl and R- hydrogen or lower alkyl; or group ROCHC(O) where Rmeans unsubstituted phenyl or phenyl substituted with similar or different substituents from group involving lower alkyl and halide; B - divalent residue of the formula -NHCHRC(O)- where Rmeans lower alkyl, lower cycloalkyl-lower alkyl, phenylmethyl, lower alkyl monosubstituted with hydroxyl, carboxyl, lower alkoxycarbonyl, aminocarbonyl, lower alkyl-aminocarbonyl or di(lower alkyl)aminocarbonyl, or radical R is absent; R- hydrogen, halide, hydroxyl, lower alkyl or lower alkoxyl; R- lower alkyl; Y - lower alkyl, lower cycloalkyl, unsubstituted phenyl or phenyl monosubstituted with halide, hydroxyl, lower alkyl or lower alkoxyl; unsubstituted phenylmethyl or phenylmethyl monosubstituted with halide, hydroxyl, lower alkyl or lower alkoxyl, or group W    Z, where W means oxo, thio, sulfinyl or sulfonyl; Z - lower alkyl, unsubstituted phenyl or phenyl monosubstituted with halide, hydroxyl, lower alkyl or lower alkoxyl, or 5- or 6-membered monovalent heterocyclic residue that contains 1 or 2 heteroatoms from group involving nitrogen, oxygen and sulfur and can be substituted with alkyl; n = 0 or 1, or their salts, in part, therapeutically acceptable acid-additive salts that were synthesized due to that (a) compound of the formula (II)where X and Rhave values indicated above is subjected for interaction with piperidine carboxamide of the formula (III)where Rand Y have values indicated above, or (b) compound of the formula (IV)where R,Rand Y have values indicated above is subjected for interaction with reactive derivative of carboxylic acid of the formula X-OH where X means group RC(O) or ROCHC(O), where Rand Rhave value indicated above, or (c) compound of above indicated formula (IV)where R,Rand Y have values indicated above is subjected for interaction with α-amino acid of the formula X-NHCHRwhere X and Rhave values indicated above in the presence of coupling agent, or (d) compound of the formula (V)where R,R,Rand Y have values indicated above, is subjected for interaction with reactive derivative of carboxylic acid of the formula X-OH where X means RC(O) or ROCHC(O) where Rand Rhave values indicated above and synthesized according to (a)-(d) the end product is isolated as free form or as acid-additive salt. The further object of invention is pharmaceutical composition containing at least one active substance and at least one pharmaceutically acceptable carrier. Active substance of composition is compound of the general formula (I)where X - groups ROC(O),RC(O),RNRC(O) where Rmeans lower alkyl, lower cycloalkyl, unsubstituted phenyl or phenyl monosubstituted with halide, hydroxyl, lower alkyl or lower alkoxyl, or disubstituted lower alkyl or halide; phenyl-lower alkyl phenyl part of which can be substituted with halide, hydroxyl, lower alkyl or lower alkoxyl; 1-naphthyl, 2-naphthyl, 5- or 6-membered monovalent heterocyclic residue that contains 1 or 2 heteroatoms from group involving nitrogen, oxygen and sulfur and can be substituted with lower alkyl, 2-quinolinyl or 3-quinolinyl, and R- hydrogen or lower alkyl, or group ROCHC(O) where Runsubstituted phenyl or phenyl substituted with similar or different substituents from group involving lower alkyl and halide; B - divalent residue of the formula -NHCHRC(O)- where Rmeans lower alkyl, lower cycloalkyl, lower cycloalkyl-lower alkyl, phenylmethyl, lower alkyl monosubstituted with hydroxyl, carboxyl, lower alkoxycarbonyl, aminocarbonyl, lower alkyl-aminocarbonyl or di(lower alkyl)aminocarbonyl, or radical R is absent; R- hydrogen, halide, hydroxyl, lower alkyl or lower alkoxyl; R- lower alkyl; Y - lower alkyl, lower cycloalkyl, unsubstituted phenyl or phenyl monosubstituted with halide, hydroxyl, lower alkyl or lower alkoxyl, unsubstituted phenylmethyl or phenylmethyl monosubstituted with halide, hydroxyl, lower alkyl or lower alkoxyl, or group W    Z, where W means oxo, thio, sulfinyl or sulfonyl; Z - lower alkyl, unsubstituted phenyl or phenyl monosubstituted with halide, hydroxyl, lower alkyl or lower alkoxyl, or 5- or 6-membered monovalent heterocyclic residue that contains 1 or 2 heteroatoms from group involving nitrogen, oxygen and sulfur and can be substituted with lower alkyl; n = 0 or 1, or its therapeutically acceptable acid-additive salt taken at effective amount. EFFECT: improved methods of synthesis.