Novel derivatives of imidazolidine, method of obtaining such derivatives, their application in production of a pharmaceutic agent, pharmaceutic agent as such and method of obtaining a pharmaceutic agent

摘要

Imidazolidine derivatives (I) are new. Imidazolidine derivatives of formula (I) are new. W = R<1>-A-C(R<13>), R<1>-A-C(R<13>)=C or a group (i) or (ii), whose ring systems may contain one or two independent N, O or S heteroatoms and may optionally be mono- or polyunsaturated and/or be substituted by one or more independent R<13> groups or by 1 or 2 double-bonded O and/or S atoms; L = C(R<13>) or N; m1, m2 = 0-6 (provided that m1 + m2 = 1-6); Y = CO, C(=S) or CH2; A = a direct bond, 1-6C alkylene, 3-7C cycloalkylene, phenylene, phenylene-(1-6C alkyl), phenylene-(2-6C alkenyl) or a 5- or 6-membered optionally substituted heterocycle, provided that the phenylenealkyl and phenylenealkenyl groups are bound to R<1> via the aromatic ring; B = 1-6C alkylene, 2-6C alkenylene, phenylene, phenylene-(1-3C alkyl), (1-3C alkylene)-phenyl or (1-3C alkylene)-phenyl-(1-3C alkyl), where the 1-6C alkylene and 2-6C alkenylene groups are optionally substituted; E = tetrazolyl, (R<8>O)2P(O), R<10>OSO2, R<9>NHSO2, R<6>CO, R<7>CO, R<10>CO, CHO, R<8>O-CH2, R<8>CO-OCH2, R8aO-CO-O-CH2 or (R<8>O)2P(O)-O-CH2; R = H, 1-8C alkyl, 3-12C cycloalkyl, 3-12C cycloalkyl-1-8C alkyl, 6-14C aryl, 6-14C aryl-1-8C alkyl, heteroaryl or heteroaryl-1-8C alkyl (all aryl being optionally substituted); R<1> = H, 1-10C alkyl or fluoroalkyl, 3-12C cycloalkyl, 3-12C cycloalkyl-(1-8C alkyl), R<21>-(6-14C aryl), R<21>-(6-14C aryl)-(1-8C alkyl), Het, Het-(1-8C alkyl) or X-NH-C(=NH)R<20>, X<1>-NH-R<20>, R<21>-O-R<20>, R<21>N(R<21>)-R<20>, R<21>-CO, R<21>-O-CO, R<22>N(R<21>)CO, R<2>CO-N(R<21>), R<21>O-N=, O= or S=; X = H, 1-6C alkyl, (1-6C alkyl)carbonyl, (1-6C alkoxy)carbonyl, (1-10C alkyl)carbonyloxy-(1-6C alkoxy)carbonyl, optionally substituted 6-14C arylcarbonyl or aryloxycarbonyl, (6-14C aryl)-(1-6C alkoxy)carbonyl, CN, OH, 1-6C alkoxy, (6-14C aryl)-(1-6C alkoxy) or amino; X<1> = as for X or is R'-NH-C(=N-R''); R', R'' = as for X; R<2> = H, 1-8C alkyl, optionally substituted 6-14C aryl or (6-14C aryl)-(1-8C alkyl) or 3-8C cycloalkyl; R<3> = e.g. H, 1-10C alkyl or fluoroalkyl, optionally substituted 6-14C aryl, 6-14C aryl-(1-8C alkyl), heteroaryl or heteroaryl-(1-8C alkyl), R<11>NH, CON(CH3)R<4>, CONHR<4>, COOR<21>, COOR<15>, CON(CH3)R<15> or CONHR<15>; R<4> = H or optionally substituted 1-10C alkyl; R<5> = 6-14C aryl or 6-14C aryl-1-8C alkyl (both being optionally aryl substituted) or mono-or bicyclic 5-12 membered heterocyclic R<6> = an amino or imino acid, an optionally alkylated or arylalkylated azaamino acid or a di-, tri- or tetrapeptide which may be esterified, amidated or protected; R<7> = an N-bound 5-10 membered saturated mono- or polycyclic heterocycle which is optionally substituted; R<8> = H, 1-10C alkyl, or optionally substituted 6-14C aryl or 6-14C aryl-(1-8C alkyl); R8a = as for R8, but is not H; R<9> = H, aminocarbonyl, (1-10C alkyl)aminocarbonyl or (3-8C cycloalkyl)aminocarbonyl; R<10> = e.g. OH, 1-10C alkoxy, 6-14C aryl-(1-8C alkoxy) or 6-14C aryloxy, or (R<8>)2NCO-(1-6C alkoxy)(the aryl groups in R<10> may all be substituted); R<11> = H, R12a, R12aCO, CHO, R12a-OCO, R12b-CO, R12b-C(=S), R12a-SO2 or R12b- SO2; R12a = 1-10C alkyl, 2-8C alkenyl, 2-8C alkynyl, 3-12C cycloalkyl, 3-12C cycloalkyl-(1-8C alkyl), 6-14C aryl, 6-14C aryl-(1-8C alkyl), heteroaryl or heteroaryl-(1-8C alkyl), where the aromatic groups are optionally substituted; R12b = NH2, di(1-10C alkyl)amino or R12a-NH; R<13> = H, 1-6C alkyl or fluoroalkyl, 6-14C aryl, 6-14C aryl-(1-6C alkyl), 3-8C cycloalkyl or 3-8C cycloalkyl-(1-6C alkyl), where the aromatic groups are optionally substituted; R<15> = R<16>-(1-6C alkyl) or R<16>; R<16> = 6-24 membered bi- or tricyclic group containing up to 4 N, O or S heteroatoms which is optionally substituted by 1-4C alkyl or oxo; R<21> = H, 1-8C alkyl, 3-12C cycloalkyl, 3-12C cycloalkyl-(1-8C alkyl), 6-14C aryl, 6-14C aryl-(1-8C alkyl), Het or Het-(1-8C alkyl), where the alkyl groups are optionally fluorinated and the aryl groups are optionally substituted; R<22> = R<21>, R<21>O, R<21>N(R<21>), R<21>CO, R<21>O-CO, R<21>N(R<21>)-CO, R<21>N(R<21>)-C(=N(R<21>)) or R<21>-CO-N(R<21>); R<30> = e.g. R<32), R<32), R<32>-S(O)n-R<31> or R12a-OCO-N(R)-R<31>; provided that R<30> is not R<32>-CO-R<31> when W = R<1>-A-C(R<13>), A is a direct bond and R<1> and R<13> are H; R<31> = R<33>-R<34>-R<35>-R<36>, where the R<36> is bound to the imidazolyl group on (I); R<32> = H, 1-8C alkyl or fluoroalkyl, 2-8C alkenyl, 2-8C alkynyl, 3-12C cycloalkyl, 3-12C cycloalkyl-(1-8C alkyl), 6-12C bicycloalkyl, 6-12C bicycloalkyl-(1-8C alkyl), 6-12C tricycloalkyl, 6-12C tricycloalkyl-(1-8C alkyl), 6-14C aryl, heteroaryl or heteroaryl-(1-8C alkyl), where the aryl and heteroaryl groups are optionally substituted; R<20>, R<33> = a direct bond or 1-6C alkylene; R<34> = 1-8C alkylene, 3-12C cycloalkylene, 6-12C bicycloalkylene, 6-12C tricycloalkylene, or optionally substituted 6-14C arylene or heteroarylene; R<35> = a direct bond or 1-8C alkylene; R<36> = a direct bond, CO or S(O)n; Het = 4-14 membered mono- or polycyclic aromatic or non-aromatic ring which contains 1-4 N, S or O heteroatoms and is optionally substituted; e,h = 0 or 1; n = 1 or 2. A full set of definitions is given in the DEFINITIONS (Full Definitions) field. An Independent claim is also included for preparation of (I).