Synthesis and Pharmacological Activity of a New Series of 1‐(1H‐Indol‐4‐yloxy)‐3‐(2‐(2‐methoxyphenoxy)ethylamino)propan‐2‐ol Analogs

Abstract

β-Adrenergic receptor antagonists are important therapeutics for the treatment of cardiovascular disorders. In the group of β-blockers, much attention is being paid to the third-generation drugs that possess important ancillary properties besides inhibiting β-adrenoceptors. Vasodilating activity of these drugs is produced through different mechanisms, such as nitric oxide (NO) release, β2 -agonistic action, α1 -blockade, antioxidant action, and Ca(2+) entry blockade. Here, a study on evaluation of the cardiovascular activity of five new compounds is presented. Compound 3a is a methyl and four of the tested compounds (3b-e) are dimethoxy derivatives of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol. The obtained results confirmed that the methyl and dimethoxy derivatives of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol and their enantiomers possess α1 - and β1 -adrenolytic activities and that the antiarrhythmic and hypotensive effects of the tested compounds are related to their adrenolytic properties.

Chirality sensing of bioactive compounds with amino alcohol unit via circular dichroism

“…The final spectrum was obtained using the software SpecDis v. 1.70 49 Initially, our attention was focused on pharmaceutical agents 1 and 2 with the secondary amine group, which exhibit affinity to α 1and β 1 -adrenoceptors, particularly in the form of the S-enantiomer. 45 Both enantiomers 1 and ent-1, as well as amino alcohol 2 mixed with Rh 2 -core, did not exhibit ECD signals in CH 3 CN, which is consistent with previous observations made for adrenaline-type compounds. 37 For this reason, the spectra of these molecules were measured in CHCl 3 .…”

“…45 Amino alcohols 3 and 4 were purchased from Sigma-Aldrich (St. Louis, MO) and used without further purification. 45 Amino alcohols 3 and 4 were purchased from Sigma-Aldrich (St. Louis, MO) and used without further purification.…”

“…Synthesis, physicochemical characteristics and pharmacological activity of tested compounds 1, ent-1 and 2 have been described previously in the literature. 45 Amino alcohols 3 and 4 were purchased from Sigma-Aldrich (St. Louis, MO) and used without further purification.…”

Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents

“…We used the compound ARC-239 as a starting point in the design of selective alpha 2B-AR ligands with antiplatelet activity, assuming that it can be deprived of the alpha 1 adrenergic activity, by changing the substitution pattern at the phenylpiperazine moiety. It has been reported that ortho -methoxyphenyl group is privileged for alpha 1 A receptor affinity 18 , 19 . Therefore, in order to obtain selective alpha 2B-AR ligands, we replaced the ortho -methoxyphenyl group with meta-substituted phenyl moiety or with bulkier heteroaromatic rings, all acceptable for alpha 2B-AR binding site restrictions, while maintaining the 4,4-dimethylisoquinoline-1,3(2 H ,4 H )-dione scaffold unchanged ( Figure 1 ).…”

Multitarget 1,4-Dioxane Compounds Combining Favorable D2-like and 5-HT1A Receptor Interactions with Potential for the Treatment of Parkinson’s Disease or Schizophrenia

“…The novel compounds were prepared following the procedure described in Scheme . The suitable amines 14 – 20 , commercially available or prepared according to previously reported procedures, − were reacted with the iodo derivative 21 or the tosyl derivative 22 in 2-methoxyethanol, to give the final compounds 7 , 9 , 11 – 13 , and the intermediates 23 and 24 . The 3- and 4-hydroxy derivatives 8 and 10 , respectively, were prepared by cleavage of the benzyl group of 23 and 24 with 4% formic acid in methanol in the presence of 10% palladium on activated charcoal as a catalyst.…”