Adrenergic Agents. 7. Synthesis and β-Adrenergic Agonist Activity of Several 2-Pyridylethanolamines

Jen, Timothy; Frazee, James S.; Schwartz, Mark S.; Kaiser, Carl

doi:10.1021/jm00220a600

Cited by 11 publications

(1 citation statement)

References 5 publications

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“…1). Based on PCILO molecular orbital calculations and NMR observations, we proposed that the structure of propranolol is an extended one, as shown in Figure 2, and not a folded structure as proposed earlier by Jen and Kaiser [7]. Our earlier results indicate that the conformation about C1-O1l bond (i.e., 71) is cis, while 7 2 , 7 4 , 7 5 , and 7 6 are in the trans configuration.…”

Section: Structure Of Propranololsupporting

confidence: 59%

Structure and function of propranolol: A β‐adrenergic blocking drug

Phadke¹,

Kumar²,

Hosur³

et al. 1981

Int J of Quantum Chemistry

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In our earlier studies using quantum chemical methods we had proposed that propranolol has an extended structure. These results were confirmed using proton NMR. We have now carried out extensive magnetic resonance and model building studies to examine the interaction of this drug with model membranes. The effect of propranolol on organization of lipid bilayers has been studied using ESR spin labeling technique. Spin label Tempo and spin labeled stearic acid (5 SASL) have been used to monitor changes in the fluidity of model membranes. Presence of the drug is found to fluidize the lipids. In case of 0.2M dipalmitoyl phosphatidyl choline (DPPC), presence of drug (0.1M) is found to decrease the gel-liquid crystalline phase transition temperature by about 10°C. The order parameter measured from the spectrum of 5 SASL shows a 4% decrease on incorporation of the drug in membranes. I3C spin lattice relaxation time ( T I ) measurements have been carried out for different nuclear sites of the drug. The aromatic moiety shows a high degree of molecular rigidity when the drug is bound to the lipid bilayers. The oxypropanolamine group is however relatively flexible. It appears from these studies that the aromatic group binds strongly to the hydrophobic regions of the lipid bilayer, while the oxypropanolamine moiety remains relatively free and lies in the hydrophilic region. The 13C chemical shifts indicate the involvement of the @-hydroxyl group in hydrogen bonding with the lipids. The NH: group may be involved in electrostatic interactions with the negatively charged phosphate group of the lipid bilayers.

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Section: Structure Of Propranololsupporting

confidence: 59%

Structure and function of propranolol: A β‐adrenergic blocking drug

Phadke¹,

Kumar²,

Hosur³

et al. 1981

Int J of Quantum Chemistry

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ThePasserini Reaction

2005

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Isocyanides are a very special class of organic compounds, which may behave as acyl anion equivalents. However, with very few exceptions, isocyanides do not react with carbonyl compounds in the absence of an acid. In this chapter, all reactions of a carbonyl compound or an acetal with an isocyanide are considered. These are processes that frequently, but not invariably, result in the incorporation of an acid residue in the final product. In the classic Passerini reaction, discovered in 1921 by Mario Passerini, the acid is always a carboxylic acid and the products alpha‐acyloxy amides. A more recent variation, which is often referred to as the Passerini reaction as well, employs a variety of mineral (H+) or Lewis acids (LA) to afford alpha‐hydroxy amides. These compounds may also be formed in the presence of carboxylic acids such as formic acid or trifluoracetic acid. Interactions of isocyanides with carbonyl compounds and some protic or Lewis acids can also lead to a large variety of products other than alpha‐hydroxy amides, including several heterocyclic systems. These Passerini‐type reactions are discussed. Acetals can also react with isocyanides in the presence of Lewis acids. The usual products are alpha‐alkoxy amides. The classic Passerini reaction is one of the oldest multicomponent reactions and is the first based on isocyanides to be discovered. This method is experiencing a growing interest. Its scope has been expanded by employing bifunctional substrates able to undergo secondary reactions. In this way, a larger variety of products can be synthesized and complex biologically active substances can be accessed quickly. Modifications that form products different from alpha‐acyloxy amides or alpha‐hydroxy amides, especially those leading to heterocycles, may find useful applications in synthesis.

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One‐Pot Synthesis of N‐Substituted β‐Amino Alcohols from Aldehydes and Isocyanides

Cioc

Niet

Janssen

et al. 2015

Chemistry A European J

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A practical two-stage one-pot synthesis of N-substituted β-amino alcohols using aldehydes and isocyanides as starting materials has been developed. This method features mild reaction conditions, broad scope, and general tolerance of functional groups. Based on a less common central carbon-carbon bond disconnection, this protocol complements traditional approaches that involve amines and various carbon electrophiles (epoxides, α-halo ketones, β-halohydrins). Medicinally relevant products can be prepared in a concise and efficient way from simple building blocks, as demonstrated in the synthesis of the antiasthma drug salbutamol. Upgrading the synthesis to an enantioselective variant is also feasible.

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Adrenergic Agents. 7. Synthesis and β-Adrenergic Agonist Activity of Several 2-Pyridylethanolamines

Cited by 11 publications

References 5 publications

Structure and function of propranolol: A β‐adrenergic blocking drug

Structure and function of propranolol: A β‐adrenergic blocking drug

ThePasserini Reaction

One‐Pot Synthesis of N‐Substituted β‐Amino Alcohols from Aldehydes and Isocyanides

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