Antihypertensive agents. Synthesis and biological properties of 2-amino-4-aryl-2-imidazolines

Abstract

The synthesis and antihypertensive activity of a series of 2-amino-4-aryl-2-imidazolines are described. Although halogenated aryls and primary 2-amino or 2-methylamino groups are particularly suitable for good antihypertensive activity, an obvious correlation of physical parameters of the aryl substituents or amine groups with antihypertensive effects is not observed. Members of this series are potent adrenergic neuronal blocking agents; they also affect uptake and release of heart norepinephrine and prevent reserpine-induced ptosis. However, none of these biological effects correlate with antihypertensive activity in DOCA rats. One compound, 19, is particularly effective, after oral or subcutaneous administration, in several hypertensive models.We have synthesized a series of 2-amino4-aryl-2-imidazolines (V and VI) which incorporates the structural features of benzyl-and phenethylguanidines. These types of guanidines are believed to affect blood pressure by their actions at peripheral sympathetic nerve terminals.1"3 This series of imidazolines is also chemically related to 2-(2,6-dichloroanilino)-2-imidazoline (catapres), a potent hypotensive agent, which appears to act mainly by a central mechanism.4Many of the imidazolines (V and VI) are potent antihypertensive agents in hypertensive rat models, and we have attempted to relate some relevant biological actions and physical properties of these agents to their antihypertensive effects.Chemistry. The 2-amino4-aryl-2-imidazolines (Table I) were synthesized from ß-aminophenethylamines III as t Presented in part before the Division of Medicinal Chemistry, 163rd National Meeting of the American Chemical Society, Boston, Mass., April 10, 1972. shown in Scheme I. Primary amine derivatives V were obtained by cyclizing the ß-aminophenethylamines with cyanogen bromide (method 10). The 2-substituted amino compounds VI were obtained by cyclizing the primary ß-aminophenethylamines with carbon disulfide, followed by Smethylation with methyl iodide and displacement of methyl mercaptan with various amines (method 13). The hydrazones 37-40 were prepared by condensation of the hydrazine 36 with aldehydes or acetone (method 14).Infrared spectra of the 2-amino4-aryl-2-imidazolines are consistent with a delocalized guanidinium system. They exhibit strong NH absorption in the 3100-3400-cm"1 region rather than in the ammonium region. Their strong C=N absorption at 1680 and 1595 cm"1 is characteristic of the disubstituted guanidinium ion.5The ß-aminophenethylamine intermediates III (Table II)were prepared by several routes (A, B, and C) as shown in Scheme I. The unsubstituted diamine 51 and the 4-MeO de-140

Stereoselective Strecker and Carbamate Annulation Methodology for the Synthesis of 1‐Amino‐1,2,5‐trideoxy‐2,5‐imino‐L‐iditol

“…[25] however, in our hands none of the desired α-aminonitriles 9a were observed, even after prolonged reaction times (24 h). To prevent formation of the cyanohydrin and other impurities, the much more soluble and nucleophilic Ph 2 CHNH 2 was utilized, [26,27] which, with increased steric bulk, could also lead to enhanced diastereoselectivity. Aldehyde 8 was thus treated with Ph 2 CHNH 2 , KCN, as the nitrile source, and Al 2 O 3 ( Table 1, Entry 2).…”

Fourier Transform Infrared (FTIR) spectroscopy to monitor the cellular impact of newly synthesized platinum derivatives

“…1) have been synthesized using the methods we detailed previously (16)(17)(18)(19). Briefly, the diamines have been obtained starting from diversely substituted benzaldehyde derivatives and through the hydrocyanation of their corresponding imines followed by the reduction of the nitrile (21). Then the complexes were isolated by reaction of the diamines with K 2 PtCl 4 (precipitation, filtration, washing with 2 N HCl and drying at 60˚C under vacuum) (22).…”

“…Then the complexes were isolated by reaction of the diamines with K 2 PtCl 4 (precipitation, filtration, washing with 2 N HCl and drying at 60˚C under vacuum) (22). All of these compounds have been characterized by 1 H-and 13 C-NMR and IR (16)(17)(18)(19)21,22 The cells were incubated at 37˚C in sealed (airtight) Falcon plastic dishes (Nunc, Invitrogen SA, Merelbeke, Belgium) in a humidified atmosphere of 5% CO 2 . The cells were kept in exponential growth phase in MEM medium supplemented with 10% fetal bovine serum (FBS), 1% penicillin/ streptomycin (an antibiotic/antimycotic solution) and 1% kanamycin to prevent mycoplasms.…”

Application of chitosan-based magnetic organic-inorganic hybrid nanocatalyst for the multicomponent synthesis of

“…This reaction is one of the most direct and efficient methods for the synthesis of α-amino nitriles. The resulting α-amino nitriles are very useful precursors for the synthesis of α-amino acids 6,7 and nitrogen containing heterocycles such as thiadiazoles and imidazoles 8,9 and other biologically useful molecules. In continuation of our interest in the application of new catalysts in organic synthesis via MCRs 11 , herein, efficient and selective syntheses of ߙ-amino nitrile derivatives were carried out using different aromatic aldehydes with amines and trimethylsilyl cyanides in the presence of a catalytic amount of magnetically recoverable chitosan supported magnetic nanoparticles in ethanol at ambient temperature in high yields (Scheme 1).…”