Patent TW-565572-B (TW)
Title: Bicyclic compounds, preparation thereof and use in pharmaceutical compositions
Inventor: ARCAMONE FEDERICO
IPC: A61P29/00
Filed: 1996-03-13
Granted: 2003-12-11
Abstract: This invention relates to novel compounds of general formula (I) and to pharmaceutical compositions containing them. Bicycl compounds of general formula (I), wherin: Y=X1=X2=X3=X4=X5=X6=-CO-NH-, wherein at least one of R1, R2, R3, R4 groups is hydrophilic and the remaining groups are hydrophobic; m=n=1 wherein the hydrophilic group is a group L-Q wherein L is a chemical bond or a inear or branched C1-6 alkyl group and Q is chosen in the group consisting of: eventually substituted mono-, di- or triglycosidic residue selected, form the group consisting of: D or L ribose, D or L arabinose, D or L xylose, D or L lyxose, D or L allose, D or L altrose, D or L glucose, D or L mannose, D or L gulose, D or L idose, D or L galactose, D or L talose, D or L allulose, D or L fructose, D or L sorbose, D or L tagatose; 5-deoxy-D or L-arabinose, 2-deoxy-D or L-glucose, 2-deoxy-D or L-galactose, 2-deoxy-D or L-arabinose, 2-deoxy-D or L-ribose, D or L fucose, D or L ramnose; D-glucosamine, D-mannosamine, D-galactosamine, daunosamine, acosamine and N-acylate derivates thereof with lower fat acids, i.e.containing a N-formylic, acetylic, propionilic, butyric residue; glucuronic acid; galacturonic acid; cellobiose, lactose, maltose, D-lactosamine, cellotriose, maltotriose; tris (hydroxyl-methy1)methy1, D or L arabitol, D or L erythrol, D or L perseitol, D or L ribitol, D or L sorbitol, D or L xylitol; or those from the residue of tartaric acid, glucaric acid, gluconic acid, bycine guinic acid, mucic acid, glucosaminic acid. Linear, branched or cyclic C1-6 alkyl chain containing one or more group chosen among amine or carboxyl wherein the hydrophobic group is sclected from the following; (a) groups corresponding to Cn H2n+1 wherein n=0, 1-4; (b) linear or branched-alkyl groups corresponding to Cn H2n-U-W wherein n=1-4; U=O, COO, CONH, S and W=alkyl-,aryl- or alkylaryl-group containing from 1 to 15 c atoms; (c) (CH2)n-C6H3-A-B wherein n=0, 1-3; A and B, placed in any of the ortho, meta or para positions, same or different from one another, represent H, halogen, OR, NHR, NR2, CH3, SR, wherein R is an alkyl-, aryl-or alkylaryl-group with less than 10 C atoms; (d) (CH2)n-C6H10R', wherein n=0, 1-3 and R'=H, C1-3 alkyl; (e) (CH2)n-heterocyclem wherein n=0, 1-3 and by the term heterocyclic imidazolyl-2-yl, indolyl-3-yl, furanyl-3-ly, piridy1-3-yl, imidazolyl-3-yl are meant; (f) a-(CH2)s-group wherein s=3, 4 eventually OH-substituted or condensed with an aromatic group, which cyclizes with one of the two adjacent X1-6 group in order to produce the side chain of proline, hydroxyproline, octahydroindol-2-carboxylic acid, tetrahydroiso-quinolinic acid, (g) the side chain of a natural hydrophobic amino acid selected from the group consisting of: glycine, alanine, valine, leucine isoleucine, methionine; (h) the side chain of a natural hydrophilic amino acid selected from the group consisting of: serine, threonine, cysteine, aspartic acid, glutamic acid, t-carboxyglutamic acid, arginine, ornythine, lysine, suitably substituted in order to render it hydrophobic; (i) the side chain of non-natural hydrophobic amino acids selected from the group consisting of: norleucine, norvaline, alloisoleucine, ciclohexylglycine (chg), alpha-amino-n-butyric-acid (Aba), ciclohexylalanine (cha), aminophenylbutyric acid (Pba), mono-and di-substitued phenylalonines in ortho, meta and para positions of the benzene ring with one or more of the following groups: C1-10 alkyl, C1-10 alkoxy, halogen, beta-2-thienylalnine, beta-3-thienylalanine, beta-2-furanylalanine, beta-3-furanylalanine, beta-2-piridylalanine, beta-3-piridylalanine, beta-4-piridylalanine, beta-(1-naphty1)alanine, beta-(2-naphty1)alanine, 0-alkyated serine-threonine-tyrosine-derivatives, S-alkyl cysteine, S-alkyl homocysteine, N-alkyl lysine, N-alkyl ornithine, N-alkyl 2,3 diaminopropionic acid.