Tejani-Butt S M, Brunswick D J
J Med Chem. 1986 Aug;29(8):1524-7. doi: 10.1021/jm00158a035.
Although (-)-[125I]iodopindolol (IPIN) can be used to label beta-adrenergic receptors in the central nervous system in vivo, use of this ligand for receptor imaging studies in humans may be limited due to its relatively poor penetration into the brain. As a first step toward the development of radioligands for imaging studies, we report the synthesis and measurement of in vitro binding affinity to beta-receptors of a series of 1-(substituted amino)-3-(4-indolyloxy)-propan-2-ol derivatives. The synthesized compounds vary widely in their lipophilicity as measured by their distribution coefficients between phosphate buffer and octanol at pH 7.4. The affinity of these compounds for beta-receptors, as measured by their inhibition of binding of IPIN to rat cortical and cerebellar membranes in vitro, ranges from 2- to 100-fold less potent than pindolol; the most potent compounds have Ki values of 2-5 nM. The radiolabeled analogues of some of these compounds may prove useful for receptor imaging studies.
虽然（-）-[¹²⁵I]碘吲哚洛尔（IPIN）可用于在体内标记中枢神经系统中的β-肾上腺素能受体，但由于其进入大脑的能力相对较差，该配体在人体受体成像研究中的应用可能受到限制。作为开发用于成像研究的放射性配体的第一步，我们报告了一系列1-（取代氨基）-3-（4-吲哚氧基）-丙-2-醇衍生物的合成及其与β受体体外结合亲和力的测定。通过在pH 7.4条件下测定它们在磷酸盐缓冲液和辛醇之间的分配系数可知，合成的化合物在亲脂性方面差异很大。通过体外抑制IPIN与大鼠皮质和小脑膜的结合来测定，这些化合物对β受体的亲和力比吲哚洛尔低2至100倍；最有效的化合物的Ki值为2-5 nM。其中一些化合物的放射性标记类似物可能对受体成像研究有用。
