Highlights•We propose properties related to drug–transporter interactions and drug
attrition.•This space consists of compounds with PSA> 75 and c log P< 3.•This space …

Highlights•Reactive metabolites (RMs) are thought to underlay idiosyncratic adverse drug
reactions (IADRs) which are one of the common causes of drug discontinuation.•RMs have …

Most small-molecule drug candidates fail before entering the market, frequently because of
unexpected toxicity. Often, toxicity is detected only late in drug development, because many …

Many adverse drug reactions are thought to be caused by electrophilically reactive drug
metabolites that conjugate to nucleophilic sites within DNA and proteins, causing cancer or …

Two 2-aminoimidazole-based inhibitors, LY3031207 (1) and LY3023703 (2), of the
microsomal prostaglandin E synthase-1 (mPGES-1) enzyme were found to cause drug …

Structure–activity relationship (SAR)-based read-across is an important and effective
method to establish the safety of a data-poor target chemical (structure of interest (SOI)) …

Aims LY3031207, a novel microsomal prostaglandin E synthase 1 inhibitor, was evaluated
in a multiple ascending dose study after nonclinical toxicology studies and a single …

Benznidazole is the drug of choice for the treatment of Chagas disease, but its metabolism in
humans is unclear. Here, we identified and characterized the major benznidazole …

Electrophilically reactive drug metabolites are implicated in many adverse drug reactions. In
this mechanism—termed bioactivation—metabolic enzymes convert drugs into reactive …

In this study, an efficient synthesis of 2, 4, 5-trisubstituted imidazoles was developed via
cyclocondensation starting from o-dione, substituted aromatic aldehyde and ammonium …