Synthesis, structure and quantitative structure-activity relationships of sigma receptor ligands, 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl) piperazines.
A set of the title compounds having different substituents (R1, R2) on their phenyl groups was synthesized to find sigma receptor binding affinity. Among the compounds, 2b (R1 = R2 = Cl) has the most potent sigma 1-binding activity, while 2a (R1 = R2 = H, SA4503) was most selective to sigma 1 over sigma 2 receptor. The crystal structures of 2a and 2b were shown, by X-ray crystallography, to be similar except for the one torsional angle of their propylene parts. Quantitative structure-activity relationship study suggested the affinity of the compounds to the sigma 1 receptor was dependent on the electronic feature, Swain-Lupton's R or Sz that was derived by molecular orbital method, of R1 and R2.
Fujimura
K
K
Developmental Research Division, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Matsumoto
J
J
Niwa
M
M
Kobayashi
T
T
Kawashima
Y
Y
In
Y
Y
Ishida
T
T
D000701:Analgesics, Opioid / Q000737:chemistry / Q000378:metabolism; D000927:Anticonvulsants / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D006146:Guanidines / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008970:Molecular Weight; D010423:Pentazocine / Q000737:chemistry / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D000927:Anticonvulsants; D006146:Guanidines; D008024:Ligands; D010879:Piperazines; D017480:Receptors, sigma; C050232:1,3-ditolylguanidine; D010423:Pentazocine