Patent DE-10064823-A1 (DE)
Title: New (hetero)aryl-substituted aliphatic carboxylic acid derivatives, useful as integrin receptor ligands for treating, e.g. atherosclerosis, restenosis, rheumatoid arthritis, cancer, osteoporosis or hypertension
Inventor: GENESTE HERVE
IPC: C07D213/74
Filed: 2000-12-22
Abstract: (Hetero)aryl-substituted aliphatic carboxylic acid derivatives (I) are new.  (Hetero)aryl-substituted aliphatic carboxylic acid derivatives of formula (I) and their salts, prodrugs, pure enantiomers or diastereomers and tautomers are new.  T  = COOH, a group hydrolyzable to COOH or bioisostere of COOH;  U  = -(Xu)a-(CR1R2)b-(CH2)c-, -(Xu)a-(CR1R2)b-C(R1)=C(R2)c- or -(Xu)a-(CR1R2)b-CC-;  a  = 0 or 1;  Xu  = -(CR3R4)d-, O or S;  b, c, d  = 0 - 2;  R1 - R4  = H, T, OH or halo; or 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, 3-7C cycloalkyl, mono- or di-(1-6C alkyl)-aminoalkyl, 1-2C alkylene-T, 2C alkenylene-T, 2C alkynylene-T, aryl or aralkyl (all optionally substituted (os));  or R1 + R2, R3 + R4 or R1 + R3  = group (completing an os 3-7 membered ring containing 0-3 of O, S and N as heteroatom(s));  G  = mono- or bicyclic 6-10C aryl (os) or 5-10C heteroaryl residue (substituted by U and X in adjacent positions);  X  = CO, CONR'1, NR'1CO, NR'1, S, SO, SO2, SO2NR'1, NR'1SO2, CS, NR'1CS, CS-O, O-CS, CO-O, O-CO, O, CC, CR'2-O-CR'3, CR'2R'3, CR'2R'3-NR'3, C(=CR'2R'3), CR'2=CR'3, CR'2(OR'4)-CR'3, CR'2CR'3(OR'4) or 4-11 membered, mono- or polycyclic cycloaliphatic or aromatic ring (os and containing 0-6 double bonds and 0-6 of O, S and N as heteroatom(s));  R'1  = H or 1-8C alkyl, 2-8C alkenyl, 2-8C alkynyl, OR'5, 3-7C cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, (1-6C) alkylcarbonyl, (1-6C) alkoxycarbonyl, 1-6C alkylsulfonyl, aralkoxycarbonyl, aralkylcarbonyl, arylcarbonyl, arylsulfonyl, heteroarylcarbonyl, aralkylsulfonyl, heteroarylsulfonyl or heteroaralkylsulfonyl (all os);  R'2, R'3  = H, OH or (1-6C alkyl, 1-4C alkoxy, 2-6C alkenyl, 2-6C alkynyl, cycloalkylalkyl, 3-7C cycloalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl (all os);  R'4, R'5  = H or 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, cycloalkylalkyl, 3-7C cycloalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl (all os);  A  = 4-8 membered, monocyclic, saturated, unsaturated or aromatic ring (os and containing 1-4 of O, S and N as heteroatom(s)), 9-14 membered, polycyclic, saturated, unsaturated or aromatic ring (os and containing 1-6 of O, S and N as heteroatom(s) or  -C(=Z)-Z';  Z, Z' = O, S or N (os);  R18, R 19  = H or 1-8C alkyl, 2-6C alkenyl, 2-6C alkynyl, (1-4C) alkoxy-(1-5C) alkyl, mono- or dialkylaminoalkyl, acylaminoalkyl, aryl, heterocycloalkyl, heterocycloalkenyl, heteroaryl, 3-7C cycloalkyl, 3-7C cycloalkyl-(1-4C) alkyl, aralkyl, heterocycloalkyl-(1-4C) alkyl, heterocycloalkenyl-(1-4C) alkyl, heteroaralkyl, SO2R20, COOR20, CONR20R21 or COR20 (all os);  R20, R21 = H or 1-8C alkyl, 2-6C alkenyl, 2-6C alkynyl, (1-4C) alkoxy-(1-5C) alkyl, mono- or dialkylaminoalkyl, acylaminoalkyl, aryl, heterocycloalkyl, heterocycloalkenyl, heteroaryl, 3-7C cycloalkyl, 3-7C cycloalkyl-(1-4C) alkyl, aralkyl, heterocycloalkyl-(1-4C) alkyl, heterocycloalkenyl-(1-4C) alkyl or heteroaralkyl (all os); and E  = spacer element covalently linking A with G, such that the number of atomic bonds along the shortest possible route through E is 2-15.