Patent NZ-510528-A (NZ)
Title: 2, 4-pentadienoic acid derivatives having selective activity for retinoid X (RXR) receptors
Inventor: VASUDEVAN JAYASREE
IPC: A61P25/28
Filed: 1999-09-20
Abstract: A compound of Formula 1, Formula 2 or of Formula 3 where X is O, S, or (CR1R1)n where n is 0, 1 or 2; Y is a bivalent radical having Formula 4 or Formula 5 where o is an integer from 1 to 4 o Y is a bivalent aryl or 5 or 6 membered heteroaryl radical having 1 to 3 heteroatoms selected from N, S and O, the aryl or heteroaryl groups being unsubstituted, or substituted with 1 to 3 C1-6 alkyl or with 1 to 3 C1-6 fluoroalkyl groups with the proviso that when the compound is in accordance with Formula 2 then Y is not a 5 or 6 membered ring; X1 is S or NH; R1 is independently H, lower alkyl of 1 to 6 carbons, or lower fluoroalkyl of 1 to 6 carbons; R2 is independently H, lower alkyl of 1 to 6 carbons, OR1, adamantyl, or lower fluoroalkyl of 1 to 6 carbons, or the two R2 groups jointly represent an oxo (=O) group with the proviso that when the compound is in accordance with Formula 2 then at least one of the R2 substituents is branched-chain alkyl or adamantyl; R3 is hydrogen, lower alkyl of 1 to 6 carbons, OR1, fluoro substituted lower alkyl of 1 to 6 carbons, halogen, NO2, NH2, NHCO(C1 - C6)alkyl, or NHCO(C1 - C6)alkenyl; A is COOH or a pharmaceutically acceptable salt thereof, COOR8, CONR9R10, -CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CH(OR13O), -COR7, CR7(OR12)2, CR7(OR13O), or Si(C1-6alkyl)3, where R7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R8 is an alkyl group of 1 to 10 carbons, (trimethylsilyl)alkyl where the alkyl group has 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R8 is phenyl or C1-6 lower alkylphenyl. R9 and R10 independently are hydrogen, an alkyl group of 1 to 10 carbons, a cycloalkyl group of 5-10 carbons, phenyl, hydroxyphenyl or lower alkylphenyl, R11 is lower alkyl of 1 to 6 carbons, phenyl or lower alkylphenyl, R12 is lower alkyl of 1 to 6 carbons, and R13 is a divalent alkyl radical of 2-5 carbons, and R14 is alkyl of 1 to 10 carbons, fluoro-substituted alkyl of 1 to 10 carbons, alkenyl of 2 to 10 carbons and having 1 to 3 double bonds, alkynyl having 2 to 10 carbons and 1 to 3 triple bonds, or carbocyclic aryl selected from the group consisting of phenyl, C1 - C10-alkylphenyl, naphthyl, C1 - C10-alkylnapthyl, phenyl-C - C10alkyl, napthyl-C1 - C10alkyl, C1 C10-alkenylphenyl having 1 to 3 double bonds, C1 - C10-alkynylphenyl having 1 to 3 triple bonds, phenyl-C1 - C10alkenyl having 1 to 3 double bonds, phenyl-C1 - C10alkenyl having 1 to 3 triple bonds, hydroxy alkyl of 1 to 10 carbons, hydroxyalkenyl having 2 to 10 carbons and 1 to 3 double bonds, hydroxyalkynyl having 2 to 10 carbons and 1 to 3 triple bonds, acyloxyalkyl of 1 to 10 carbons, acyloxyalkenyl having 2 to 10 carbons and 1 to 3 double bonds, and acyloxyalkynyl of 2 to 10 carbons and 1 to 3 triple bonds where the acyl group is represented by COR8, or R14 is a 5 or 6 membered heteroaryl group having 1 to 3 heteroatoms, the heteroatoms being selected from the group consisting a O, S, and N, the heteroaryl group being unsubstituted  or substituted with a C1 to C10 alkyl group, with a C1 to C10 fluoroalkyl group, or with halogen, and the dashed line in Formula 4 represents a bond a absence of a bond; or a pharmaceutically acceptable salt of the compound.