Structure-Activity study of retinoid agonists bearing substituted dicarba-closo-dodecaborane. Relation between retinoidal activity and conformation of two aromatic nuclei.
We have investigated the structure activity relationships of the potent retinoid agonist, 4-[4-(2-propyl-1,2-dicarba-closo-dodecaboran-l-yl)phenylamino]benzoic acid (BR403), which we have previously reported. Substitution of a methyl group on the aromatic nucleus or a methyl group on the nitrogen atom, or replacement of the amino group with ether, methylene, carboxyl or 1,1-ethylene greatly decreased the activity. The relatively planar conformation at the phenyl-N-phenyl moiety seems to play a critical role in the appearance of the biological activity.
Endo
Y
Y
Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan. yendo@mol.f.u-tokyo.ac.jp
Iijima
T
T
Yaguchi
K
K
Kawachi
E
E
Inoue
N
N
Kagechika
H
H
Kubo
A
A
Itai
A
A
D000818:Animals; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology; D001880:Boranes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016754:Boron Neutron Capture Therapy; D019556:COS Cells; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D018168:Receptors, Retinoic Acid / Q000819:agonists; D012176:Retinoids / Q000819:agonists*; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects
C444859:4-(4-(2-propyl-1,2-dicarba-closo-dodecaboran-l-yl)phenylamino)benzoic acid; D001565:Benzoates; D001880:Boranes; D018168:Receptors, Retinoic Acid; D012176:Retinoids