Imidazolines, structure-activity

This procedure was utilized by the same authors to synthesize a large library of 4-carbohydroxamido-2-(aryl or alkyl)-2-imidazolines, some of which exhibited excellent LpxC inhibitory and antibacterial activities. The technical maneuvers in the syntheses of these compounds and their structure-activity relationships are comprehensively covered by the authors in their paper. 

The only aspect of octopaminergic transmission for which a relatively large amount of structure-activity data is available relates to the properties of OA-receptors themselves. Agonists that stimulate these systems and antagonists that block them, are known and such compounds exist in several structural groups. The three major groups of agonists currently identified are phenylethylamines amidines and imidazolines. 

The workers at American Cyanamid present some of the synthetic and biological characteristics of the sulfur analogs of their imidazoline family of herbicides. This is an example of replacing the carbonyl of the imidazoli-none with an isosteric moiety. This is an interesting account of the synthesis and structure-activity relationships in a very active series of herbicides. 

Thus, initially, an extensive structure-activity relationship study was performed the data of this study suggested the existence of a new class of receptors specific for imidazoline-like compoimds different from the classical a-adrenergic receptors [1]. 

Timmermans, P. B. M. W. M., Hoefke, W., Stahle, H., van Zwieten, P. A., Structure activity relationships in clonidine-like imidazolines and related compounds, Progr. Pharmacol. 3 1-104,1980. 

We have taken advantage of the ease of generating Ru-NHC complexes in situ to help define structure-activity relationships for imidazolin-2-ylidene and imidazolidin-2-ylidene derivatives used as ancillary ligands in metathesis catalysts. For this purpose, a wide range of new imidazolium and imidazoli-nium chlorides bearing aromatic substituents was synthesized. These ionic precursors were deprotonated with potassium tert-butoxide or sodium hydride and combined wMi [RuCl2(p-cymene)]2 in chlorobenzene at 60°C. Cyclooctene was then added and its polymerization was allowed to proceed for 2 h under visible light illumination (Eq. 3)." ... 

In contrast to this, there are no such structural constraints on a-adrenergic agonists or antagonists. Some of the most active a-sympathomimetic agents in fact contain an imidazoline moiety as part of the pharmacophore. The appropriate ring system can be... 

Tolazoline (41) has clear structural similarities to the imidazoline a-agonists, such as naphazoline and xylometazoline, but does not have the lipophilic substituents required for agonist activity. Phentolamine (40) is also an imidazoline a-antagonist but the nature of its binding to a-adrenoceptors is not elearly understood. 

A pharmacophore does not represent a real molecule or a real association of functional groups but is a purely abstract concept that accounts for the common molecular interaction capacities of a group of compounds toward their target structure. The pharmacophore can be considered to be the largest common denominator shared by a set of active molecules. This definition discards a misuse often found in the MEDICINAL CHEMISTRY literature, which consists of naming as pharmacophores simple chemical functionalities such as guanidines, sulfonamides, or dihydroimidazoles (formerly imidazolines), or typical structural skeletons such as flavones, phenothiazines, prostaglandins, or steroids. 

Tolazoline and the structurally related imidazoline tetrahydrozoline may be H2 receptor agonists since tolazoline-induced acid stimulation in the dog can be blocked by burimamide, metiamide and cimetidine and both imidazolines induce characteristic -agonist effects on isolated guinea pig atria preparations which can be blocked by metiamideJ Clonidine, like the imidazolines, has a-adrenergic agonist activity... 

---