Basic Principles of the CIP-System and Proposals for a Revision†

TL;DR: In this article , the presence of helical character and chirality using a vector-based charge density perspective instead of energetic or structural measures was investigated for α,ωdisubstituted [4]cumulenes as the end groups are torsioned.

Abstract: This review profiles ten marketed pharmaceuticals approved by the US Food and Drug Agency within the last five years that feature aliphatic fluorination – a key structural feature pivotal to their biological activity. These include ivosidenib, developed for the treatment of acute myeloid leukemia and cholangiocarcinoma (bile duct cancer); ubrogepant, approved for the acute treatment of migraines; asciminib, prescribed for the treatment of chronic my­eloid leukemia in the chronic phase; omaveloxolone, used in the treatment of Friedreich’s ataxia, a rare genetic disorder causing progressive damage to the spinal cord, peripheral nerves, and brain; flurpiridaz (18F), a radioactive diagnostic agent for myocardial perfusion imaging by positron emission tomography; upadacitinib, designed to address several inflammatory and autoimmune conditions, including rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn’s disease, ankylosing spondylitis, and non-radiographic axial spondyloarthritis; tezacaftor, approved for the treatment of cystic fibrosis as an effective remedy; alpelisib, prescribed for the treatment of breast cancer, effectively inhibiting tumor growth and abnormal cell proliferation; pretomanid, used in combination therapies for the treatment of extensively drug-resistant and multi-drug-resistant tuberculosis; and atogepant, approved for the preventive treatment of migraines in adults, targeting both episodic and chronic migraines. Molecules featuring aliphatic fluorination present challenges due to higher production costs and the complexity of predicting their biological profiles. However, the undeniable medicinal benefits of aliphatic fluorination invigorate this area of research, paving the way for the development of more innovative drugs to enter the pharmaceutical market. Beyond the incorporation of aliphatic fluorine atoms, six of the pharmaceuticals discussed in this review feature residues of amino acids or their derivatives as pivotal structural design ele­ments. Another characteristic shared by all these drugs is their chirality, with each molecule possessing between one and six stereogenic carbons. Special attention should be directed toward the phenomenon of self-disproportionation of enantiomers (SDE), a behavior observed in enantiomerically enriched compounds. The SDE properties of chiral drugs, particularly those containing fluorine and/or amino acid residues, represent a vital public safety concern, necessitating rigorous evaluation of enantiomeric purity. Additionally, caution should be exer­cised in light of growing public concerns over the potential harmful effects of fluorine on human health. Since fluoride is recognized as the final metabolite of organic fluorinated compounds, patients prescribed fluorine-containing drugs should consult their physicians about non-fluorinated alternatives where available or take steps to limit fluoride exposure from other sources, such as fluoridated water and industrially produced foods treated with fluorinated agrochemicals. Despite these concerns, it remains an undeniable fact that fluorine-containing drugs are indispensable in modern medicine. They provide life-saving treatments, improve quality of life, and drive medical innovation addressing urgent health challenges and laying the foundation for future advancements in healthcare.

TL;DR: The prospect for computer‐aided refinement of stereoselective enzymes is further validated by simulating the ester hydrolysis by the wild‐type and mutants of CalB, focusing on the challenge of dealing with strong steric effects and entropic contributions.

TL;DR: In this article, the authors propose an approach to bezeichnungen fur partielle Konformationen (Konstellationen) abgeleitet.

TL;DR: In this article, the authors considered derivatives of triptycene and fluorene whose barriers to rotation were of the order of 30 kcal/mol, and showed that the barrier to rotation is high enough to give rise to rotamers.