Preparation of 2-aminoindane analogs.Curry, Kenneth (IGT Pharma Inc., Can.).
PCT Int. Appl. (2001),
CAN 134:86547, AN 2001:31449
65 pp.
Patent EP1194400
Abstract2-Aminoindane analogs I [R1, R2 = H or an acidic group selected from carboxy, phosphono, phosphino, sulfono, sulfino, borono, tetrazolyl, isoxazolyl, -(CH2)n-carboxy, -phosphono, -phosphino, -sulfono, -sulfino, -borono, -tetrazolyl, or -isoxazolyl, where n = 1-6; X is an acidic group selected from carboxy, phosphono, phosphino, sulfono, sulfino, borono, tetrazolyl, or isoxazolyl; Y is a basic group selected from aliph. or arom. primary, secondary, or tertiary amino, quaternary ammonium salts, imidazolyl, guanidino, boronoamino, allyl, urea, or thiourea; m = 0 or 1; R3-6 = H, nitro, amino, halo, tritium, trifluoromethyl, trifluoroacetyl, sulfo, carboxy, carbamoyl, or sulfamoyl] or their stereoisomers or pharmaceutically acceptable salts were prepd. as modulators of metabotropic glutamate receptors (mGluRs) for use in treating diseases of the central nervous system.
Thus, 2-amino-2-carboxy-1-indaneacetic acid (cis and trans isomers) were prepd. by a multistep procedure starting from 1,2-phenylenediacetonitrile. The cAMP assay showed that the cis isomer is a Group II/III mGluRs antagonist (EC50 = 1.2x10-9 M) and the trans isomer is a Group II/III mGluRs agonist (EC50 = 1.1x10-7 M).
The present invention relates to therapeutically active 2-aminoindane analogs of formula (I). Also provided is a method of preparing compounds of formula (I), and pharmaceutical compositions comprising the compounds. The novel compounds act as modulators of metabotropic glutamate receptors and, as such, are useful in treating diseases of the central nervous system related to the metabotropic glutamate receptor system.