Substituted imidazoline derivatives, their preparation, their use, and pharmaceutical compositions containing them

• Main Authors: STILZ, HANS ULRICH DR, WEHNER, VOLKMAR DR, SCHMIDT, WOLFGANG DR, SEIFFGE, DIRK DR
• Format: Patent
• Language: English; French; German
• Published: 25.06.2003
• Edition: 7
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Imidazolidine derivatives (I) are new. Imidazolidine derivatives of formula (I) are new. W = R -A-C(R ), R -A-C(R )=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 groups or by 1 or 2 double-bonded O and/or S atoms; L = C(R ) 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 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 O)2P(O), R OSO2, R NHSO2, R CO, R CO, R CO, CHO, R O-CH2, R CO-OCH2, R8aO-CO-O-CH2 or (R 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 = H, 1-10C alkyl or fluoroalkyl, 3-12C cycloalkyl, 3-12C cycloalkyl-(1-8C alkyl), R -(6-14C aryl), R -(6-14C aryl)-(1-8C alkyl), Het, Het-(1-8C alkyl) or X-NH-C(=NH)R , X -NH-R , R -O-R , R N(R )-R , R -CO, R -O-CO, R N(R )CO, R CO-N(R ), R 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 = as for X or is R'-NH-C(=N-R''); R', R'' = as for X; R = H, 1-8C alkyl, optionally substituted 6-14C aryl or (6-14C aryl)-(1-8C alkyl) or 3-8C cycloalkyl; R = 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 NH, CON(CH3)R , CONHR , COOR , COOR , CON(CH3)R or CONHR ; R = H or optionally substituted 1-10C alkyl; R = 6-14C aryl or 6-14C aryl-1-8C alkyl (both being optionally aryl substituted) or mono-or bicyclic 5-12 membered heterocyclic R = 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 = an N-bound 5-10 membered saturated mono- or polycyclic heterocycle which is optionally substituted; R = 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 = H, aminocarbonyl, (1-10C alkyl)aminocarbonyl or (3-8C cycloalkyl)aminocarbonyl; R = e.g. OH, 1-10C alkoxy, 6-14C aryl-(1-8C alkoxy) or 6-14C aryloxy, or (R )2NCO-(1-6C alkoxy)(the aryl groups in R may all be substituted); R = 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 = 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 = R -(1-6C alkyl) or R ; R = 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 = 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 = R , R O, R N(R ), R CO, R O-CO, R N(R )-CO, R N(R )-C(=N(R )) or R -CO-N(R ); R = e.g. R<32)<R)N-CO-N(R)-R , R<32)<R)N-C(=S)-N(R)-R , R -S(O)n-R or R12a-OCO-N(R)-R ; provided that R is not R -CO-R when W = R -A-C(R ), A is a direct bond and R and R are H; R = R -R -R -R , where the R is bound to the imidazolyl group on (I); R = 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 , R = a direct bond or 1-6C alkylene; R = 1-8C alkylene, 3-12C cycloalkylene, 6-12C bicycloalkylene, 6-12C tricycloalkylene, or optionally substituted 6-14C arylene or heteroarylene; R = a direct bond or 1-8C alkylene; R = 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).