Emerging modes-of-action in drug discovery
An increasing focus on complex biology to cure diseases rather than merely treat symptoms is transforming how drug discovery can be approached, and expands the arsenal of drug modalities and modes-of-actions that can be leveraged to modify diseases.
Advances in indoleamine 2,3-dioxygenase 1 medicinal chemistry
Structure–function relationships of IDO1 and structure–activity relationships of inhibitors are discussed with an outlook on next generation IDO1 ligand.
High throughput methods to measure the propensity of compounds to form intramolecular hydrogen bonding
Implementation of IMHB considerations in drug discovery needs robust and validated descriptors to experimentally verify the propensity of compounds to exhibit IMHBs.
pyridazines privileged structures?
Compared to carbocyclic drug molecules, pyridazine-containing drugs present additional interaction possibilities, as illustrated here for the antirhinoviral agent R 61837.
Progress on lamellarins
The latest developments towards the synthesis of lamellarins, their structure–activity relationship and advances in the mechanism of action are described.
Molecular obesity, potency and other addictions in
Molecular Obesity is the tendency for lead optimisation to yield candidate molecules that are unfit for their continued survival towards becoming a drug. Reasons for this and other issues are discussed.
Proteochemometric modeling as a tool to design selective compounds and for extrapolating to novel targets
Proteochemometric modeling is founded on the principles of QSAR but is able to benefit from additional information in model training due to the inclusion of target information.
chloride to nitrile transformation: medicinal and synthetic chemistry
This review highlights the medicinal and synthetic chemistry relevance of replacing an aromatic chloride motif with an aromatic nitrile.
Discovery of novel selective Sigma-1
ligands as cognitive enhancers
Novel drug-like and selective Sigma-1 ligands have been prepared and pharmacologically evaluated in a mouse model of cognitive deficits.
Identification of target family directed bioisosteric replacements
Shown are exemplary replacements of chemical groups that are bioisosteric for individual target families.
prodrugs of ciprofloxacin as DNA-gyrase inhibitors: synthesis, antiparasitic evaluation and docking studies
Novel ester prodrugs of ciprofloxacin proved to be extremely efficient against Plasmodium falciparum and Toxoplasma gondii. Molecular modeling and computational calculations were used to understand the mechanisms of action of these drugs.
phosphonic acids as fructose 1,6-bisphosphatase
inhibitors with potent glucose-lowering activity
Phosphonic acid-containing oxazoles were discovered as potent inhibitors of fructose 1,6-bisphosphatase. Several oxazoles demonstrated significant glucose-lowering activity in rats after intravenous dosing.
New positive allosteric modulators of the metabotropic
glutamate receptor 2 (mGluR2). Identification and synthesis of N-propyl-5-substituted isoquinolones
N-propyl-5-substituted isoquinolones were identified as mGluR2 PAMs via high-throughput screening (HTS). Initial SAR exploration led to the identification of compound 20.
Comparison of two- and three-dimensional activity landscape representations for different compound data sets
A network-like similarity graph is mapped onto the surface of a 3D landscape model illustrating similarities and differences between these two approaches for graphical SAR analysis.
Global assessment of scaffold hopping potential for current
A scaffold-based target network is shown together with scaffold pairs having different scaffold hopping potential for a given target.
Dissecting the allosteric FXR modulation: a chemical biology approach using guggulsterone as a chemical tool
FXR allosteric pockets might act as potential targets for small molecules to selectively interfere with the metabolic action of the receptor.
Discovery of 2-phenoxyacetamides as inhibitors of the Wnt-depalmitoleating enzyme NOTUM from an X-ray fragment screen
Optimization of fragment hit 3 identified isoquinoline 45 as a potent inhibitor of NOTUM with an unexpected flipped binding mode.
Discovery of (aza)indole derivatives as novel respiratory syncytial virus fusion inhibitors
A new class of (aza)indole derivatives have been identified as potent RSV fusion inhibitors.
Expansion of the structure–activity relationships of BACE1 inhibitors by harnessing diverse building blocks prepared using a unified synthetic approach
The structural diversity of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors was expanded by harnessing diverse building blocks that had been prepared via a unified lead-oriented synthetic approach.
Neuroligin-2-derived peptide-covered polyamidoamine-based (PAMAM) dendrimers enhance pancreatic β-cells' proliferation and functions
The nanoscale composite improved β-cell functions in terms of rate of proliferation, glucose-stimulated insulin secretion, resistance to cellular stress and functional maturation.
Succinct synthesis of saturated hydroxy fatty acids and in vitro evaluation of all hydroxylauric acids on FFA1, FFA4 and GPR84
A concise synthetic protocol enables rapid receptor screening of hydroxy fatty acid.
Pyrazolo[3,4-d]pyrimidines as sigma-1 receptor ligands for the treatment of pain. Part 2: Introduction of cyclic substituents in position 4
A SAR study identified the 4-(1-methylpyrazol-5-yl) derivative, 12f, as a selective σ1R antagonist with a good ADMET profile and potent antinociception.
Pyrazolo[3,4-d]pyrimidines as sigma-1 receptor ligands for the treatment of pain. Part 1: 4-acylamino derivatives
The 4-acylaminopyrazolo[3,4-d]pyrimidine 9a was identified as a highly selective σ1R antagonist, showing as well substantial antinociceptive properties.
Scaffold hopping via ANCHOR.QUERY: β-lactams as potent p53-MDM2 antagonists
The discovery of a novel potent p53-MDM2 antagonistic small molecule scaffold using a mix of computational, chemistry and biophysical techniques.
Chiral disubstituted piperidinyl ureas: a class of dual diacylglycerol lipase-α and ABHD6 inhibitors
The enantioselective synthesis and structure–activity relationships of deoxy-iminosugar-based triazole ureas as dual inhibitors of DAGLα and ABHD6 were reported.
About this collection
MedChemComm is delighted to present this themed collection containing articles by speakers at the International Symposium on Medicinal Chemistry, organized by the European Federation for Medicinal Chemistry.
This ongoing collection will be updated regularly with new articles so please return to this page to see the collection grow.