Patent SK-158098-A3 (SK)
Title: Substituted imidazoline derivatives, their preparation, their use and pharmaceutical compositions containing them
Inventor: WEHNER VOLKMAR
IPC: C07K5/117
Filed: 1998-11-17
Abstract: 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)N-CO-N(R)-R<31>, R<32)<R)N-C(=S)-N(R)-R<31>, 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).