Synthesis, resolution, and preliminary evaluation of trans-2-amino-6(5)-hydroxy-

2020-03-30 05:42:26

15 14 trans Phenyl dihydro

责任者: Claudi, F;Cingolani, GM;DiStefano, A;Giorgioni, G;Amenta, F;Barili, P;Ferrari, F;Giuliani, D 单位: UNIV CAMERINO,SEZ ANAT UMANA,I-62032 CAMERINO,MC,ITALY.;UNIV MODENA,IST FARMACOL,I-41100 MODENA,ITALY. 来源出处: JOURNAL OF MEDICINAL CHEMISTRY, v 39, OCT 11 1996, p 4238- 4246 摘要: The present work reports the synthesis of enantiomeric pairs of the trans-2-amino-6-hydroxyl-phenyl-2,3-dihydro-1H-indene [(+)-14a, (-)-14a] and trans-2-amino-5-hydroxy-1-phenyl-2,3-dihydro-1H-indene [(+)-14b, (-)-14b] and their N,N-di-n-propyl [(+)- and (-)-15a,b], N-methyl-N-allyl [(+)- and (-)-16a,b], and N-methyl-N-n-propyl [(+) and (-)-17a,b] derivatives obtained by a combination of stereospecific reactions and optical resolution. The new compounds were evaluated for their affinity at the dopamine D-1 and D-2 receptors. The amines (+)- and (-)-14a, incorporating the D-1 pharmacophore 2-phenyl-2-(3-hydroxyphenyl)ethylamine in a trans extended conformation, and their derivatives displayed D-1 and D-2 affinity in the nanomolar range. On the other hand, the enantiomers (+)- and (-)-14b, (+)- and (-)-15b displayed high affinity and selectvity for the D-1 receptor. In a preliminary behavioral study on rats (+)-14b, and to a greater extent (+)-15b, promoted episodes of intense grooming, thus indicating that they act as central D-1 agonists. The trans-2-amino-5-hydroxy-1-phenyl-2,3-dihydro-1H-indenes (+)-14b and (+)-15b represent selective D-1 agonists lacking a catechol group, which should meet the prerequisites for a central nervous system penetration. 关键词: quantum wire; split gate; electron confinement potential; far-infrared spectroscopy; electronic states; magnetotransport; nanostructure spectroscopy; electronic states; magnetotransport; nanostructure; MOLECULAR-BIOLOGY; PHARMACOLOGICAL EVALUATION; AGONIST; ANALOGS; ENANTIOMERS; ANTAGONISTS; SCH-23390; D-2; RAT ENANTIOMERS; ANTAGONISTS; SCH-23390; D-2; RAT