Teng R R, Bai L Q, Shiue C Y, Dewey S L, Arnett C D, Wolf A P, Hitzemann R J
Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973.
Int J Rad Appl Instrum B. 1990;17(8):811-7. doi: 10.1016/0883-2897(90)90030-5.
No-carrier-added (NCA) R(+)-7-chloro-8-hydroxy-3-(3'-[18F]fluoropropyl)-1-phenyl-2,3,4,5- tetrahydro-3-benzazepine (2b) (an analog of dopamine D-1 receptor ligand SCH 23390), ethyl 8-fluoro-5,6-dihydro-5-(3'-fluoropropyl)-6-oxo-4H- imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate (4b) and 3'-[18F]fluoropropyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate (6b) (analogs of the benzodiazepine RO 15-1788) were synthesized by alkylation of the corresponding nor-compound with NCA 1-[18F]fluoro-3-iodopropane in 10-15% yield (EOB) in approximately 110 min and with a mass of 2-3 nmol. Compound 2 is less potent (approximately 12-14 times) than SCH 23390 in binding to rat striatal membranes in vitro. Compounds 2b, 4b and 6b exhibit no specific anatomical distribution to mouse brain. These results suggest that the substituent at position 3 of SCH 23390, and position 5 and carboxylate group of RO 15-1788 are critical determinants both of affinity and selectivity for receptor binding, and underscores the evaluation necessary when even minor changes (C1 to C3) are made in bioactive compounds.
无载体添加（NCA）的R(+)-7-氯-8-羟基-3-(3'-[¹⁸F]氟丙基)-1-苯基-2,3,4,5-四氢-3-苯并氮杂卓（2b）（多巴胺D-1受体配体SCH 23390的类似物）、8-氟-5,6-二氢-5-(3'-氟丙基)-6-氧代-4H-咪唑并[1,5-a][1,4]苯并二氮杂卓-3-羧酸乙酯（4b）和3'-[¹⁸F]氟丙基8-氟-5,6-二氢-5-甲基-6-氧代-4H-咪唑并[1,5-a][1,4]苯并二氮杂卓-3-羧酸酯（6b）（苯并二氮杂卓RO 15-1788的类似物）通过相应的去甲化合物与NCA 1-[¹⁸F]氟-3-碘丙烷进行烷基化反应合成，产率（按放化产率计）为10 - 15%，反应时间约110分钟，产物质量为2 - 3纳摩尔。化合物2在体外与大鼠纹状体膜结合时的活性比SCH 23390低（约12 - 14倍）。化合物2b、4b和6b在小鼠脑中未表现出特定的解剖学分布。这些结果表明，SCH 23390的3位取代基以及RO 15-1788的5位和羧酸酯基团是受体结合亲和力和选择性的关键决定因素，并强调了对生物活性化合物即使进行微小变化（C1至C3）时也有必要进行评估。
