Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• introduction of α-eucaine (8) in medicine, the first synthetic local anesthetic, a compound devoid of narcotic properties and with an improved hydrolytical stability compared to cocaine [40]. Eucaines were used as anesthetics during WWI. Before the war, England used to import them from Germany, and to replace

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• -dihydro-1H-isoindolin-1-ones via acid-catalyzed dehydration and subsequent nucleophilic substitution with the corresponding secondary amines. The procedure was successfully applied to the synthesis of known local anesthetics (AL-12, AL-12B and AL-5) in their neutral forms. Keywords: anesthetics

• ][5][6][7]. AL-12, AL-12B and AL-5 (Figure 1), for example, were described as highly active local anesthetics distinctly exceeding the efficiencies of common local anesthetics such as procaine, xylocaine/lidocaine and tetracaine [8]. Their molecular structures contain the three key elements of all

• local anesthetics: (a) a lipophilic aromatic ring, (b) an amide (or ester) linker, and (c) a terminal tertiary amine [9]. The original synthesis of these bioactive compounds involved a Perkin condensation followed by an amination reaction. An alternative pathway to AL-12B has been described by Couture

Is conformation a fundamental descriptor in QSAR? A case for halogenated anesthetics

• Maria C. Guimarães,
• Mariene H. Duarte,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2016, 12, 760–768, doi:10.3762/bjoc.12.76

• suggesting that these 2D MD´s can be advantageous over some three-dimensional descriptors. Keywords: conformational analysis; isoflurane; QSAR; theoretical calculations; volatile anesthetics; Introduction Quantitative structure–activity relationship (QSAR) studies try to find a correlation between chemical

• when the molecules in a data set undergo rotational isomerization. In order to test our hypothesis, the biological activities of a set of volatile halogenated anesthetics were modelled using the recent version of the MIA-QSAR method. In addition, the suitability of applying 3D information obtained from

A quadruple cascade protocol for the one-pot synthesis of fully-substituted hexahydroisoindolinones from simple substrates

• Hong-Bo Zhang,
• Yong-Chun Luo,
• Xiu-Qin Hu,
• Yong-Min Liang and
• Peng-Fei Xu

Beilstein J. Org. Chem. 2016, 12, 253–259, doi:10.3762/bjoc.12.27

• , this method is fast and easy to implement, and it is suitable for large-scale synthesis (Scheme 1). Many isoindolinone skeletons show high biological potential as antihypertensives, anesthetics, etc. [66][67][68]. The useful hydrolyzed product rac-4a was obtained in 80% yield by treating rac-3a with

New GABA amides activating GABA_A-receptors

• Peter Raster,
• Andreas Späth,
• Svetlana Bultakova,
• Pau Gorostiza,
• Burkhard König and
• Piotr Bregestovski

Beilstein J. Org. Chem. 2013, 9, 406–410, doi:10.3762/bjoc.9.42

• subunits: two α, two β and one γ subunit [5]. Being highly expressed in the peripheral and central nervous system, GABAA-receptors represent a key therapeutic target for benzodiazepines, barbiturates, neurosteroids and general anesthetics [6][7][8]. Therefore, in spite of a large variety of existing

Trifluoromethyl ethers – synthesis and properties of an unusual substituent

• Frédéric R. Leroux,
• Baptiste Manteau,
• Jean-Pierre Vors and
• Sergiy Pazenok

Beilstein J. Org. Chem. 2008, 4, No. 13, doi:10.3762/bjoc.4.13

• anesthetics was quickly followed by applications of anti-inflammatory agents. Investigations of the anesthetic properties of α-fluorinated ethers were undertaken on the rational basis that replacement of the hydrogen atom in already known "anesthetic molecules" by fluorine should result in derivatives having

• improved thermal stabilities relative to the inhalation anesthetics in common use at that time (cyclopropane and ether), like the halo ether anesthetic Fluoroxene (Fluoromar®, F3C-H2C-O-CH=CH2). Numerous analogues [13] were prepared and evaluated (Table 1). Meanwhile, cyclic analogues bearing the

• fluorinated 1,3-dioxolanes moiety [14] have largely replaced Fluoroxene in its clinical use. Many anesthetics currently used are powerful positive allosteric modulators of GABAA [15]. Numerous new OCF3 containing compounds have been prepared, clinically evaluated and in many cases marketed as drugs with