The methyl group is one of the most commonly occurring carbon fragments in small-molecule drugs. This simplest alkyl fragment appears in more than 67 % of the top-selling drugs of 2011 and can modulate both the biological and physical properties of a molecule. This Review focuses on so-called magic methyl effects on binding potency, where the seemingly mundane change of CH to CMe improves the IC50  value of a drug candidate more than 100-fold. This discussion is followed by a survey of recent advances in synthetic chemistry that allow the direct methylation of C(sp(2) )H and C(sp(3) )H bonds. It is our hope that the relevance of the meager methyl group to drug discovery as presented herein will inspire reports on new CH methylation reactions.

Profound methyl effects in drug discovery and a call for new C-H methylation reactions.

The addition of a radical to a heteroaromatic base is commonly referred to as a Minsici reaction. Such reactions constitute a broad-set of selective CH-functionalization processes. This review describes some of the major applications of Minisci reactions and related processes to medicinal or biological chemistry, and highlights some potential developments within this area.

Minisci reactions: Versatile CH-functionalizations for medicinal chemists

Quinoline and quinazoline alkaloids, two important classes of N-based heterocyclic compounds, have attracted tremendous attention from researchers worldwide since the 19th century. Over the past 200 years, many compounds from these two classes were isolated from natural sources, and most of them and their modified analogs possess significant bioactivities. Quinine and camptothecin are two of the most famous and important quinoline alkaloids, and their discoveries opened new areas in antimalarial and anticancer drug development, respectively. In this review, we survey the literature on bioactive alkaloids from these two classes and highlight research achievements prior to the year 2008 (Part I). Over 200 molecules with a broad range of bioactivities, including antitumor, antimalarial, antibacterial and antifungal, antiparasitic and insecticidal, antiviral, antiplatelet, anti-inflammatory, herbicidal, antioxidant and other activities, were reviewed. This survey should provide new clues or possibilities for the discovery of new and better drugs from the original naturally occurring quinoline and quinazoline alkaloids.

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Biologically active quinoline and quinazoline alkaloids part I

Towards new anticancer drugs: a decade of advances in synthesis of camptothecins and related alkaloids

Camptothecins (CPTs) are cytotoxic natural alkaloids that specifically target DNA topoisomerase I. Research on CPTs has undergone a significant evolution from the initial discovery of CPT in the late 1960s through the study of synthetic small-molecule derivatives to investigation of macromolecular constructs and formulations. Over the past years, intensive medicinal chemistry efforts have generated numerous CPT derivatives. Three derivatives, topotecan, irinotecan, and belotecan, are currently prescribed as anticancer drugs, and several related compounds are now in clinical trials. Interest in other biological effects, besides anticancer activity, of CPTs is also growing exponentially, as indicated by the large number of publications on the subject during the last decades. Therefore, the main focus of the present review is to provide an ample but condensed overview on various biological activities of CPT derivatives, in addition to continued up-to-date coverage of anticancer effects.

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Perspectives on biologically active camptothecin derivatives.

Practical synthesis of (S)‐7‐(2‐isopropylamino)ethylcamptothecin hydrochloride, potent topoisomerase I inhibitor

A practical semi-synthetic method of (S)-7-(2-isopropylamino)ethylcamptothecin hydrochloride has been developed The Mannich reaction of (S)-7-methylcamptothecin with isopropylamine hydrochloride in dimethyl sulfoxide as a formaldehyde source gave the desired product in moderate yield

Duck Jin Journ

Papers

Practical synthesis of (S)‐7‐(2‐isopropylamino)ethylcamptothecin hydrochloride, potent topoisomerase I inhibitor

Practical Synthesis of (S)-7-(2-Isopropylamino)ethylcamptothecin Hydrochloride, Potent Topoisomerase I Inhibitor.