I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Privileged substructures are of potentially great importance in medicinal chemistry. These scaffolds are characterized by their ability to promiscuously bind to a multitude of receptors through a variety of favorable characteristics. This may include presentation of their substituents in a spatially defined manner and perhaps also the ability to directly bind to the receptor itself, as well as exhibiting promising characteristics to aid bioavailability of the overall molecule. It is believed that some privileged substructures achieve this through the mimicry of common protein surface elements that are responsible for binding, such as β- and gamma;-turns. As a result, these structures represent a promising means by which new lead compounds may be identified.

The combinatorial synthesis of bicyclic privileged structures or privileged substructures

Over the past decade, the most significant, conceptual advances in the field of fluorination were enabled most prominently by organo- and transition-metal catalysis. The most challenging transformation remains the formation of the parent C-F bond, primarily as a consequence of the high hydration energy of fluoride, strong metal-fluorine bonds, and highly polarized bonds to fluorine. Most fluorination reactions still lack generality, predictability, and cost-efficiency. Despite all current limitations, modern fluorination methods have made fluorinated molecules more readily available than ever before and have begun to have an impact on research areas that do not require large amounts of material, such as drug discovery and positron emission tomography. This Review gives a brief summary of conventional fluorination reactions, including those reactions that introduce fluorinated functional groups, and focuses on modern developments in the field.

/pdf/introduction-of-fluorine-and-fluorine-containing-functional-1i8kwiad20.pdf

Introduction of Fluorine and Fluorine-Containing Functional Groups

Amide bond formation is a fundamentally important reaction in organic synthesis, and is typically mediated by one of a myriad of so-called coupling reagents. This critical review is focussed on the most recently developed coupling reagents with particular attention paid to the pros and cons of the plethora of “acronym” based reagents. It aims to demystify the process allowing the chemist to make a sensible and educated choice when carrying out an amide coupling reaction (179 references).

http://www.chtf.stuba.sk/~szolcsanyi/education/files/Organicka%20chemia%20II/Prednaska%208_Aminokyseliny%20a%20peptidy/Doplnkove%20studijne%20materialy/Amide%20bond%20formation/Amide%20bond%20formation%20-%20beyond%20the%20myth%20of%20coupling%20reagents.pdf

Amide bond formation: beyond the myth of coupling reagents

There are at least two types of cannabinoid receptors (CB1 and CB2). Ligands activating these G protein-coupled receptors (GPCRs) include the phytocannabinoid Δ9-tetrahydrocannabinol, numerous synthetic compounds, and endogenous compounds known as endocannabinoids. Cannabinoid receptor antagonists have also been developed. Some of these ligands activate or block one type of cannabinoid receptor more potently than the other type. This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non-CB1, non-CB2 established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors. From these data, it is clear that some ligands that interact similarly with CB1 and/or CB2 receptors are likely to display significantly different pharmacological profiles. The review also lists some criteria that any novel “CB3” cannabinoid receptor or channel should fulfil and concludes that these criteria are not currently met by any non-CB1, non-CB2 pharmacological receptor or channel. However, it does identify certain pharmacological targets that should be investigated further as potential CB3 receptors or channels. These include TRP vanilloid 1, which possibly functions as an ionotropic cannabinoid receptor under physiological and/or pathological conditions, and some deorphanized GPCRs. Also discussed are 1) the ability of CB1 receptors to form heteromeric complexes with certain other GPCRs, 2) phylogenetic relationships that exist between CB1/CB2 receptors and other GPCRs, 3) evidence for the existence of several as-yet-uncharacterized non-CB1, non-CB2 cannabinoid receptors; and 4) current cannabinoid receptor nomenclature.

https://pharmrev.aspetjournals.org/content/pharmrev/62/4/588.full.pdf

International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2

4‐[(8‐Alkyl‐8‐azabicyclo [3.2.1]octyl‐3‐yl)‐3‐arylanilino]‐N,N‐diethylbenzamides: High Affinity, Selective Ligands for the Delta Opioid Receptor Illustrate Factors Important to Antagonist Activity.

Kappa-opioid-rezeptor-liganden

Synthesis and Transporter Binding Properties of (R)-2β,3β- and (R)-2α,3α-Diaryltropanes.

2-Arachidonylglycerol (2-Ara-Gl) was synthesized via the intermediacy of its 1,3-phenylboronic acid ester. The boronate ester is easily stable enough to enable chromatographic resolution from the corresponding 1-Ara-Gl boronate ester on normal phase elution yet immediately and completely hydrolyzes to 2-Ara-Gl and phenylboronic acid, without isomerization, by simple solution in aqueous-organic solvents. The phenylboronate ester of this 2-acylglycerol has the added advantage of being markedly more stable to both isomerization and oxidation upon storage than the labile 2-Ara-Gl.

Facile Synthesis and Stabilization of 2‐Arachidonylglycerol via Its 1,3‐Phenylboronate Ester.

Epibatidine is a potent but nonselective nAChR agonist. Its biological effects appear to be mediated largely by α4β2 nAChRs. Surprisingly, only a limited number of epibatidine analogues have been synthesized and evaluated in in vitro assays. Even fewer analogues have received in vivo pharmacological evaluation. In this paper, SAR studies directed toward epibatidine analogues will be reviewed.

F. Ivy Carroll

Papers

4‐[(8‐Alkyl‐8‐azabicyclo [3.2.1]octyl‐3‐yl)‐3‐arylanilino]‐N,N‐diethylbenzamides: High Affinity, Selective Ligands for the Delta Opioid Receptor Illustrate Factors Important to Antagonist Activity.

Kappa-opioid-rezeptor-liganden

Synthesis and Transporter Binding Properties of (R)-2β,3β- and (R)-2α,3α-Diaryltropanes.

Facile Synthesis and Stabilization of 2‐Arachidonylglycerol via Its 1,3‐Phenylboronate Ester.

Epibatidine Structure—Activity Relationships