Imidazoline selective

Imidazoline specific receptors are involved in the hypotensive effects of imidazoline selective compounds as well as of clonidine-like (hybrid) drugs. 

To examine if the higher catalytic activity and selectivity of 47a as compared to the COP-X system 46 is mainly caused by the pentaphenyl ferrocenium or by the imidazoline moiety, oxazoline 53-Cl was prepared in diastereomerically pure form starting from carboxylic acid 51 and (5)-valinol via oxazoline 52 (Fig. 27) [73]. 

The high enantioselectivity again can be rationalized by enantioface-selective alkene coordination in 63 (Fig. 35). The olefin moiety is expected to bind trans to the upper imidazoline moiety [70,73] thereby releasing the catalyst strain. Coordination at this position may, in principal, afford four different isomers assuming the stereoelectronically preferred perpendicular orientation of the alkene and the Pt(II) square plane. In the coordination mode shown, steric repulsion between both olefin substituents and the ferrocene moiety is minimized. Outer-sphere attack of the indole core results in the formation of the product s stereocenter. 

Although these two methods have found widespread application for the synthesis of free carbenes, they failed for selected saturated imidazolidin-2-ylidenes and especially in the preparation of triazolin-5-ylidenes. In these cases the free carbene species 7 can be obtained from 2-alkoxyimidazolidines 6 [44] or 5-aUcoxytriazoles [36] by thermally induced ot-elimination of an alcohol (Fig. 5). In addition to 2-aUcoxyimidazolidmes, 2-(pentafluorophenyl)imidazolidines [45, 46] have also been used for the generation of NHCs by cx-elimination. The adduct 8 eliminates acetonitrile upon heating [47] to yield the benzimidazolin-2-ylidene 9. In a more exotic procedure, imidazolium salts have been reduced electrochemically to give the free imidazolin-2-ylidenes [48]. 

Table V. Stimulation of Adenylate Cyclase and Arthropod Behavior by Selected Substituted-Phenyl Imidazolines.

The MCR toward 2//-2-imidazolines (65) has found apphcation in the construction of A(-heterocyclic carbene (NHC) complexes (74). Alkylation of the sp Af-atom with an alkyl halide followed by abstraction of the proton at C2 with a strong base (NaH, KOtBu) resulted in the formation of the free carbene species, which could be trapped and isolated as the corresponding metal complexes (Ir or Rh) [160]. The corresponding Ru-complexes were shown to be active and selective catalysts for the transfer hydrogenaticm of furfural to furfurol using iPrOH as hydrogen source [161]. 

Similarly, variously substituted 3-imidazoline nitrone reagents and the related nitroxides (363 R = O) are popular targets and have demonstrated their reactivity toward various dipolarophiles, (e.g., styrene. Scheme 1.80) (420-431). However, only one group reports the use of a 2-imidazoline nitrone (432 34), which has demonstrated complete diastereofacial selectivity in its reactions with electron-... 

Idazoxan is an imidazoline compound developed to be a potent and highly selective Oj-adrenoceptor antagonist with little interaction at Oj and P adrenoceptor or other major neurotransmitter receptors. However, like many of the imidazolines that show high affinity for adrenoceptors, idazoxan has equal or higher affinities for the recently identified imidazoline receptors. Imidazoline receptors have been shown to be present in many tissues, including human brain [De Vos et al. 1994], and have been hypothesized to be involved with the regulation of blood pressure and possibly norepinephrine release [Ernsberger et al. 1990]. 

The unmodified pyridine ring, in contrast to imidazole or imidazoline rings, is seldom associated with any specific pharmacophoric activity. It does, however, appear in a number of therapeutic agents due to the fact that benzene rings in biologically active compounds can often be replaced by pyridines in spite of the presence of the basic nitrogen atom. The relatively small number of pyridines discussed below thus do not reflect the frequency of their occurrence in therapeutic agents instead, examples have been selected that illustrate some facet of pyridine chemistry. 

Dehydration of monoacylated diamines using POCl3 yielded substituted imidazolines 16 and 19 (Fig. 5). Selective acylation of the primary amino group of the diamines 14 and 17 was successfully achieved using a... 

At therapeutic doses, these drugs are associated with some troublesome but relatively minor side effects including dry mouth, dizziness, and sedation. The incidence of sedation seems to be related to these drug s alpha-2 stimulatory effects. Hence, agents that are more selective for imidazoline receptors may seem better tolerated because patients are more alert and have less psychomotor slowing.104... 

Kaaja R, Manhem K, Tuomilehto J. Treatment of postmenopausal hypertension with moxonidine, a selective imidazoline receptor agonist. IntJ Clin Pract Suppl. 2004 139 26-32. 

The imidazolines (107) and (108) reacted with nitrile oxides with modest to high stereoselectivity, but low regioselectivity (91BCJ3274). Diastereo-selective reactions of the oxazolidines (109) and the imidazoline (110) have also been reported (91BCJ3274,91TA1185). As a representative example, the imidazoline (110) reacted with benzonitrile oxide (3) at room temperature to give the adducts (111) and (112) in the ratio 4 1. After separation... 

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