IMIDAZOLINE ANALOGS AS PROBES OF A-ADRENOCEPTORS

我们的目标是更好地了解结构特征 α-肾上腺素能受体激动剂和拮抗剂活性所必需的。这个 拟议的工作围绕使用咪唑啉衍生物作为 分子来探索α-肾上腺素能受体的立体化学需求。 最近，α-肾上腺素能受体被细分为α1和α2， 而且几乎没有数据可以用来刻画和优化 咪唑啉类药物与不同α-肾上腺素受体的相互作用。 我们的具体目标是(1)设计、合成、分离和表征一种 咪唑啉系列类似物，(2)在适当的情况下，至 拆分几何异构体和拆分光学异构体 各自的生物学研究，(3)开展药理研究 咪唑啉类化合物对选定组织的体外、体内和体外实验研究 α-肾上腺素能受体亚型的数量显著活性，(4) 为了研究α-肾上腺素受体上的咪唑啉光学异构体类似物 看看这与经典的Easson-Stedman假说有什么关系 苯乙醇胺，(5)检查交叉脱敏和 选择的基团试剂，试图区分 咪唑啉和苯乙醇胺类化合物在不同温度下的作用 α-肾上腺素能受体，(6)启动研究以评估 咪唑啉类似物对原代肝细胞胸腺嘧啶核苷掺入的影响 含有调节细胞生长的α1肾上腺素受体的培养，以及 (7)确定这些具有重要意义的分子 α-肾上腺素能受体活性药理活性概况 包括β-受体(β1和β2)和组胺(H-1和H-2) 感受器。 这些研究应该为替代会产生什么影响提供新的见解 有已知的咪唑啉激动剂和拮抗剂并提供新的发现 关于阿尔法1和阿尔法的立体化学要求 2-肾上腺素能受体。这些药物将加深我们对 肾上腺素能受体亚型的结构要求，并提供 治疗鼻塞、抑郁、肝细胞的更具选择性的EMAN 变性或增殖、高血压、低血压和心血管疾病 精神错乱。

Our aim is to gain a better understanding of the structural features necessary for agonist and antagonist activity at alpha-adrenoceptros. The proposed work is centered around the use of imidazoline derivatives as molecules to probe the stereochemical requirement for alpha-adrenoceptors. Recently, alpha-adrenoceptors have been subclassified alpha 1 and alpha 2, and little data is available which attempts to characterize and to optimize the interaction of imidazoline drugs with the different alpha-adrenoceptors. Our specific aims are (1) to design, synthesize, isolate and characterize a series of imidazoline analogs, (2) in those instances where appropriate, to separate geometrical isomers and resolve optical isomers for their respective biological studies, (3) to carry out pharmacological studies on the imidazoline derivatives on selected tissues in vitro, and in vivo to quantitative significant activity on the alpha-adrenoceptor subtypes, (4) to examine the imidazoline optical isomer analogs on alpha-adrenoceptors to see what the relationship is to the classical Easson-Stedman Hypothesis for phenethanolamines, (5) to examine the effects of cross desensitization and of selected group reagents in an attempt to differentiate between the action of imidazoline and phenethanolamine derivatives at alpha-adrenoceptors, (6) to initiate studies to evaluate the action of imidazoline analogs on thymidine incorporation into primary hepatocyte cultures that contain alpha 1-adrenoceptors which regulate cell growth, and (7) to determine for these molecules possessing significant alpha-adrenoceptor activities a profile of pharmacological activity including beta-adrenoceptor (beta 1 and beta 2) and histamine (H-1 and H-2) receptors. The studies should provide new insights into what effects substitutions have on known imidazoline agonist and antagonist and provide new findings as to the stereochemical requirements for alpha 1 and alpha 2-adrenoceptors. These drugs will enhance our understanding of the structural requirements for the subtypes of adrenoceptors and provide a more selective emans of treating nasal congestion, depresion, liver cell degeneration or proliferation, hypertension, hypotension and cardiovascular disorders.