Patent CZ-298898-A3 (CZ)
Title: Novel imidazolidine derivatives, process of their preparation, their use as a medicament and pharmaceutical compositions in which such derivatives are comprised
Inventor: WEHNER VOLKMAR DR
IPC: C07K5/02
Filed: 1998-09-17
Abstract: Imidazolidine derivatives of formula (I) and their stereoisomers and salts are new. W = C(R13)AR1 or C=CHR1; Z = O or S; a = direct bond or 1-2C alkylene; B = 1-6C alkylene (optionally substituted by 1-8C alkyl), 2-8C alkenyl, 2-8C alkynyl, 3-10C cycloalkyl, (3-10C)cycloalkyl(1-6C)alkyl, optionally substituted 6-14C aryl, optionally ring-substituted (6-14C)aryl(1-6C)alkyl, optionally substituted heteroaryl or optionally ring-substituted heteroaryl(1-6C)alkyl, 2-6C alkenylene, phenylene, phenylene(1-3C)alkylene or (1-3C)alkylenephenylene; E = tetrazolyl, PO(OR8)2, SO3H, SO2NHR9 or COR10; R = H, 1-8C alkyl, 3-12C cycloalkyl, (3-12C)cycloalkyl(1-8C)alkyl, optionally substituted 6-14C aryl, optionally ring-substituted (6-14C)aryl(1-8C)alkyl, optionally substituted heteroaryl or optionally ring-substituted heteroaryl(1-8C)alkyl; R10 = H, R', CHO, COR', SOR' or SO2R'; R' = 1-8C alkyl, 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, optionally substituted 6-14C aryl, optionally ring-substituted (6-14C)aryl(1-8C)alkyl, optionally substituted heteroaryl or optionally ring-substituted heteroaryl(1-8C)alkyl; R1 = optionally substituted and optionally benzo-fused phenyl, furyl, thienyl, pyrrolyl, imidazolyl or pyridyl; R2 = H, 1-8C alkyl, optionally substituted 6-14C aryl, optionally ring-substituted (6-14C)aryl(1-8C)alkyl or 3-8C cycloalkyl; R3 = H, 1-8C alkyl, optionally substituted 6-14C aryl, optionally ring-substituted (6-14C)aryl(1-8C)alkyl, optionally substituted heteroaryl, optionally ring-substituted heteroaryl(1-8C)alkyl, 3-8C cycloalkyl, (3-8C)cycloalkyl(1-8C)alkyl, 6-12C bicycloalkyl, (6-12C)bicycloalkyl(1-8C)alkyl, 6-12C tricycloalkyl, (6-12C)tricycloalkyl(1-8C)alkyl, 2-8C alkenyl, 2-8C alkynyl, NHR11, CON(Me)R4, CONHR4, COOR14, CON(Me)R15 or CONHR15; R4 = H or 1-10C alkyl (optionally substituted by one or more of OH, 1-8C alkyl, R5, optionally substituted 3-8C cycloalkyl, COOH, CONH2, mono- or di(1-18C alkyl)carbamoyl, optionally ring-substituted (6-14C)aryl(2-9C)alkoxycarbonyl, 2-9C alkoxycarbonyl, CO-Het, COR6, tetrazolyl and CF3); R5 = optionally substituted 6-14C aryl, optionally ring-substituted (6-14C)aryl(1-8C)alkyl or optionally substituted mono- or bicyclic 5-12-membered heterocyclyl containing 1-3 heteroatoms selected from N, O and S; R6 = optionally protected residue of an amino acid, imino acid, optionally N-(1-8C)-alkylated or N-(optionally ring-substituted (6-14)aryl(1-8C)alkylated) aza-amino acid or a dipeptide (optionally in ester or amide form); R8 = H, 1-18C alkyl optionally substituted 6-14C aryl or optionally ring-substituted (6-14C)aryl(1-8C)alkyl; R9 = H, CONH2, (1-18C alkyl)carbamoyl, (3-8C cycloalkyl)carbamoyl, optionally substituted (6-14C aryl)carbamoyl, 1-18C alkyl, optionally substituted 6-14C aryl or 3-8C cycloalkyl; R10 = OH, 1-18C alkoxy, optionally ring-substituted (6-14C)aryl(1-8C)alkoxy, optionally substituted 6-14C aryloxy, (2-9C)alkanoyloxy(1-6C)alkoxy, (7-15C)aroyloxy(1-6C)alkoxy, NH2 or mono- or di(1-18C alkyl)amino; R11 = H, R12a, COR12a, CHO, COOR12a, COR12b, CSR12b, SO2R12a or SO2R12b; R12a = 1-18C alkyl, 2-8C alkenyl, 2-8C alkynyl, 3-12C cycloalkyl, (3-12C)cycloalkyl(1-8C)alkyl, optionally substituted 6-14C aryl, optionally ring-substituted (6-14C)aryl(1-8C)alkyl, optionally substituted heteroaryl, optionally ring-substituted heteroaryl(1-8C)alkyl or R15; R12b = NH2, di(1-18C alkyl)amino or NHR12a; R13 = H, 1-6C alkyl, optionally substituted 6-14C aryl, optionally ring-substituted (6-14C)aryl(1-6C)alkyl, 3-8C cycloalkyl or (3-8C)cycloalkyl(1-6C)alkyl; R15 = R16 or 1-6C alkyl substituted by R16; R16 = 6-24-membered bicyclic or tricyclic group that is saturated or partially unsaturated, optionally contains 1-4 heteroatoms selected from N, O and S and is optionally substituted by one or more of 1-4C alkyl and oxo; Het = N-bonded 5-10-membered saturated mono- or polycyclic heterocyclic group that can contain 1-4 additional heteroatoms selected from O, N and S, can be C-substituted and can be substituted on additional N atoms by H, Rh, CHO, CORh or COORh; Rh = 1-8C alkyl, 3-8C cycloalkyl, (3-8C)cycloalkyl(1-8C)alkyl, optionally substituted 6-14C aryl or optionally ring-substituted (6-14C)aryl(1-8C)alkyl; and e, h = 0 or 1.